Epidural Steroid Injection Overuse: Measuring the Terrain First

Epidural steroid injection overuse is a pattern of repeat procedures with no measured reason or result behind them. The correction is a documented metabolic, cognitive and balance baseline taken before the next procedure and taken again after it.

Utilization data record how often the needle is used and nothing about the patient it was used on. A baseline measured before the next procedure is the outcome field the claims never had.

Epidural steroid injection overuse is almost never visible in one chart. It appears in aggregate: in traditional Medicare the transforaminal epidural rose 579 percent between 2000 and 2010, and in commercial claims patients averaged 4.46 spinal procedures in the twelve months after their first. Chapter 12 of The Pained Brain, by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD, defends the procedure as a bridge and rejects it as a destination. For a practice, the variable that separates the two is measurable: whether anything about the patient’s terrain was documented before the next procedure and documented again after it.

Why can’t claims data show epidural steroid injection overuse?

The utilization literature shares a limitation that matters more than its magnitude: none of it carries an indication or an outcome. In a cohort of 196,332 commercially insured patients, the busiest tenth of providers performed 36.6 percent of spinal procedures, nine times the lowest tenth. After a first lumbar medial branch ablation in 44,936 patients, repeats accumulated to 45.7 percent by seven years. Across 4,108,121 patients with a lumbar degenerative diagnosis, the annual injection rate held near 10 percent, and states that injected more also operated more. Since 2019 the direction has reversed, with interventional techniques down 16.8 percent in traditional Medicare through 2024.

Both trends are uninterpretable at the patient level. A repeat ablation after genuine relief can be guideline-consistent, and claims cannot tell a planned repeat from a failure; a decline cannot tell better selection from reduced access. The same fix answers both: record a measured state of the patient that can be compared over time.

What drives repeat spinal procedures?

In a study of 31 physician organizations affiliated with 22 health systems, volume formed the base incentive for 93.3 percent of specialist incentive plans and for 83.9 percent in primary care, with quality metrics carrying a minor share of the weighting. Practices tend to cite a different driver. Surveyed, 2,106 physicians estimated a median 20.6 percent of care is unnecessary and named malpractice fear most often. Yet when 36 hospitalists rated 4,215 of their own orders, 28 percent carried some defensive motive, and those claiming the most defensive orders did not order more than their peers. Habit, referral patterns and training carry part of the pattern too, which is exactly why structure, not exhortation, has to change the default.

Epidural steroid injection overuse: what the repeat-procedure chart omits

The composite patient in the chapter arrives for his ninth epidural with imaging, a nerve study and a surgical opinion on file, and no fasting insulin, diet history or sleep history. The medication burden that accompanies that pattern is well described. Excessive polypharmacy, ten or more agents, reached 25.9 percent in a Quebec chronic pain cohort. Of 20,422 discharges of older polypharmacy inpatients, an opioid combined with a hypnotic appeared in 24.5 percent of those with chronic noncancer pain. In nursing homes, roughly one resident in twenty started on a gabapentinoid had a loop diuretic added within three months.

The two biological drivers the procedure pathway leaves unmeasured are metaflammation with insulin resistance and the iatrogenic load of the regimen itself. Neither appears in a utilization count, and both can be measured in an ordinary clinic.

A measured baseline before the next procedure

Measura [Cardiometabolic and Autonomic Health Analysis] is a testing service; it measures, does not treat, and returns results to the ordering physician. For a patient on a repeat-procedure pathway, a documented baseline might include:

• Laboratory panels for metabolic markers, with fasting insulin specified on the order
• Bioimpedance body composition, so muscle and fat compartments are tracked rather than weight
• Cognitive assessment with vestibular and balance testing when the regimen combines opioids, hypnotics or gabapentinoids, tied into the practice’s fall-prevention workflow
• Heart rate variability or broader autonomic testing when the history points toward autonomic involvement

Standing orders make the baseline reproducible instead of dependent on who staffs the clinic that day. The annual wellness visit is a natural anchor, and structured results feed the documentation that MIPS and HEDIS reporting rely on.

How does remeasurement show whether a plan worked?

The clearest demonstration that terrain moves comes from outside pain. The DiRECT trial began from the premise that type 2 diabetes requires lifelong treatment and randomized primary care practices to a structured weight-management program. Remission ran 46 against 4 percent at one year and 36 against 3 at two, with antidiabetic drugs still prescribed in 40 against 84 percent. The response was graded by weight lost: 57 percent remission at 10 to 15 kilograms and 86 percent at 15 or more. That gradient is what a practice can only see if weight, composition and metabolic markers were measured at the start.

The pain data are smaller and honest. Multidisciplinary rehabilitation improves pain by about half a point on a ten-point scale over usual care. Its larger contribution is dependency: in 1,457 patients in a three-week program, 86.74 percent of opioid users were weaned with no difference in improvement by admission dose, though 30.70 percent resumed within a year. Across 86 samples and 15,616 patients, self-efficacy predicted impairment, distress and pain prospectively, which argues for showing patients their own measured change.

Why the process reforms missed

Choosing Wisely was followed by a 4 percent relative reduction in low-value back imaging, and a value-based primary care program left back imaging at 13.8 percent in both arms. Both targeted the order, not the patient. Continuity is the counterexample: annual physician face time per person in the United States is 60.4 minutes, while 18 of 22 studies linked greater continuity with lower mortality, and among 4,552,978 Norwegians more than fifteen years with one physician carried an odds ratio for death of 0.75. Decision aids made a values-matched choice 1.75 times as likely. Measurement, continuity and a shared decision are one workflow. The preceding topic in the series is screening for cluster headache, the next is image guidance, and every study cited is in the Chapter 12 technical companion.

Frequently asked questions

References

• Abbott, Z. I., Nair, K. V., Allen, R. R., & Akuthota, V. R. (2012). Utilization characteristics of spinal interventions. The Spine Journal, 12(1), 35–43. https://doi.org/10.1016/j.spinee.2011.10.005
• Starr, J. B., Gold, L. S., McCormick, Z., Suri, P., & Friedly, J. (2019). Repeat procedures and prescription opioid use after lumbar medial branch nerve radiofrequency ablation in commercially insured patients. The Spine Journal, 20(3), 344–351. https://doi.org/10.1016/j.spinee.2019.10.005
• Reid, R. O., Tom, A. K., Ross, R. M., Duffy, E. L., & Damberg, C. L. (2022). Physician Compensation Arrangements and Financial Performance Incentives in US Health Systems. JAMA Health Forum, 3(1), e214634. https://doi.org/10.1001/jamahealthforum.2021.4634
• Rothberg, M. B., Class, J., Bishop, T. F., Friderici, J., Kleppel, R., & Lindenauer, P. K. (2014). The cost of defensive medicine on 3 hospital medicine services. JAMA Internal Medicine, 174(11), 1867–1868. https://doi.org/10.1001/jamainternmed.2014.4649
• Zahlan, G.; De Clifford-Faugère, G.; Nguena Nguefack, H. L.; Guénette, L.; Pagé, M. G.; Blais, L.; Lacasse, A. (2023). Polypharmacy and Excessive Polypharmacy Among Persons Living with Chronic Pain: A Cross-Sectional Study on the Prevalence and Associated Factors. J Pain Res, 16, 3085–3100. https://doi.org/10.2147/JPR.S411451
• Lean, M. E.; Leslie, W. S.; Barnes, A. C.; Brosnahan, N.; Thom, G.; McCombie, L.; Peters, C.; Zhyzhneuskaya, S.; Al-Mrabeh, A.; Hollingsworth, K. G.; Rodrigues, A. M.; Rehackova, L.; Adamson, A. J.; Sniehotta, F. F.; Mathers, J. C.; Ross, H. M.; McIlvenna, Y.; Stefanetti, R.; Trenell, M.; … Taylor, R. (2018). Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet, 391(10120), 541–551. https://doi.org/10.1016/S0140-6736(17)33102-1
• Huffman, K. L.; Rush, T. E.; Fan, Y.; Sweis, G. W.; Vij, B.; Covington, E. C.; Scheman, J.; Mathews, M. (2017). Sustained improvements in pain, mood, function and opioid use post interdisciplinary pain rehabilitation in patients weaned from high and low dose chronic opioid therapy. Pain, 158(7), 1380–1394. https://doi.org/10.1097/j.pain.0000000000000907
• Jackson, T., Wang, Y., Wang, Y., & Fan, H. (2014). Self-efficacy and chronic pain outcomes: a meta-analytic review. The Journal of Pain, 15(8), 800–814. https://doi.org/10.1016/j.jpain.2014.05.002
• Sandvik, H., Hetlevik, Ø., Blinkenberg, J., & Hunskaar, S. (2022). Continuity in general practice as predictor of mortality, acute hospitalisation, and use of out-of-hours care: a registry-based observational study in Norway. British Journal of General Practice, 72(715), e84–e90. https://doi.org/10.3399/BJGP.2021.0340
• Stacey, D., Lewis, K. B., Smith, M., Carley, M., Volk, R., Douglas, E. E., Pacheco-Brousseau, L., Finderup, J., Gunderson, J., Barry, M. J., Bennett, C. L., Bravo, P., Steffensen, K., Gogovor, A., Graham, I. D., Kelly, S. E., Légaré, F., Sondergaard, H., Thomson, R., … Trevena, L. (2024). Decision aids for people facing health treatment or screening decisions. Cochrane Database of Systematic Reviews, 1(1), CD001431. https://doi.org/10.1002/14651858.CD001431.pub6

Related reading

• Screening for Cluster Headache in Primary Care: A Three-Item Workflow
• Before the Diagnostic Nerve Block: What the Referring Chart Needs
• Laboratory Panels

Screening for Cluster Headache in Primary Care: A Three-Item Workflow

Screen for cluster headache in primary care with the Erwin Test, a validated three-item decision tree on pain intensity, attack duration and same-side autonomic features, with 84 percent sensitivity and 89 percent specificity. Trigger it for recurrent unilateral head or face pain, let clinical staff give it by standing order, and record the answers in a structured field.

The median patient reaches a correct cluster headache diagnosis after a decade of wrong ones. The tool that shortens that interval takes three questions and a structured field in the record.

Screening for cluster headache in primary care is a workflow problem before it is a pharmacology problem. The pooled interval from first attack to correct diagnosis is 10.43 years across 22 studies, only 21 percent of 1,134 American survey respondents were identified correctly at initial presentation, and the instrument that would close much of that gap already exists. Chapter 11 of The Pained Brain, the video above, by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD, treats the disorder as time-critical. For a practice the operational questions are narrower: where a validated screen sits in intake, and what a positive result sets in motion.

Why does cluster headache take so long to diagnose?

The 10.43-year mean needs a caveat that sharpens it. It is inflated by older cohorts, and delay has fallen by decade of onset in British and Danish series. First-contact accuracy has not kept pace. In 144 Italian and Eastern European episodic patients, 77 percent were misdiagnosed at first consultation with 2.27 diagnoses each, and 93 percent underwent instrumental or laboratory testing. In a Portuguese series of 64, before the correct label 17.2 percent had received opioids and 14.1 percent dental procedures. In an American chart-validated cohort of 75, mean delay was 12.7 years, and the excess dental, TMJ and septal diagnoses were judged very likely to be misdiagnoses rather than comorbidity.

Three drivers sustain the pattern. Attack timing is hypothalamic, and pain is delivered through the trigeminal-parasympathetic reflex, so the event resolves before examination and is silent on imaging. The third is organizational: among 218 family and emergency physicians, 15 percent rated themselves sufficiently knowledgeable, nearly half did not know autonomic features are mandatory for diagnosis, 72.5 percent of family physicians send an acute attack to the emergency department, and 92.9 percent of emergency respondents manage these patients in the lowest-acuity zone.

How accurate is screening for cluster headache in primary care?

The Erwin Test for Cluster Headache is a three-item decision tree on intensity, duration and autonomic features, validated in 319 participants including 109 with cluster headache. Reported sensitivity was 84 percent, specificity 89 percent, positive predictive value 76 percent and negative predictive value 93 percent. The design limits interpretation: single-center validation with enriched recruitment of trigeminal autonomic cephalalgia means positive predictive value in an unselected primary-care panel will run lower, and no study has yet shown the screen shortens delay. Its strengths are the negative predictive value and its brevity.

Operationally it behaves like any validated instrument: a trigger, a script, a discrete result. A defensible trigger is recurrent unilateral head or face pain, including patients returned from dental or sinus evaluation without a cause. Written as a standing order, it can be administered by clinical staff before the physician enters, and a structured field makes the answer retrievable at the next visit instead of reconstructed from unstructured notes; see getting results into the record.

Can cluster headache be mistaken for migraine?

Migraine-like features are common in cluster headache and should not be used to exclude it. In 1,604 questionnaire respondents meeting criteria, 50.1 percent had photophobia or phonophobia, 31.4 percent pain aggravated by activity and 27.5 percent nausea or vomiting, while 99.0 percent had at least one cranial autonomic feature and 96.6 percent restlessness. The authors concluded that prototypical migrainous features do not separate the two disorders.

Sex compounds the error. In a Swedish biobank of 874 re-verified patients, self-reported migraine was 29.4 percent in women against 12.5 percent in men. In a Chinese registry of 1,206, conjunctival injection was less frequent in women, 38.52 against 56.03 percent, while restlessness was identical. The woman in the exam room is more likely to present as migraine and less likely to show the red eye. Age matters as well: onset before 20 carried a mean 13.8-year delay in 400 Danish patients against 2.1 years after 40, and in the international sample 27.5 percent reported onset before 18, of whom only 15.2 percent were diagnosed before 18. Adolescent visits belong in the screening population.

What changes after a cluster headache diagnosis?

The argument for screening rests on what follows a correct label. The American Headache Society lists subcutaneous sumatriptan, zolmitriptan nasal spray and high-flow oxygen as Level A acute treatments and suboccipital steroid injection as the only Level A preventive; opioids are absent, partly because they were never trialed. Practice diverges sharply. Among 7,589 newly diagnosed commercially insured patients, the leading prescription class over the next twelve months was opioids, at 41 percent, and oxygen was claimed by 16.2 percent within seven days of diagnosis. Patients rated opioids completely or very effective in 6 percent against 54 percent for oxygen. Access is the other constraint: of 566 patients who eventually obtained oxygen, 13 percent waited two to five years, and the mean commercial wait for a new neurology visit is 49.7 days. A documented positive screen lets the plan begin during the bout rather than after it.

Documentation after a positive result

• The three screen answers, dated, in a discrete field
• Episodic or chronic classification, because response splits: galcanezumab reduced weekly attacks in episodic disease and missed its primary endpoint in chronic disease, and non-invasive vagus nerve stimulation separated the same way in two sham-controlled trials
• Prior diagnoses and procedures, dental and sinus interventions included
• For patients on verapamil, the electrocardiogram schedule: in an audit, 19 percent of 108 patients with tracings on file had an arrhythmia, and 41 percent of 217 treated patients had no tracing at all
• Refractory status against the consensus definition of at least three severe attacks weekly despite three adequate preventive trials

Where Measura fits, and where it does not

Measura [Cardiometabolic and Autonomic Health Analysis] does not diagnose primary headache disorders, and nothing in its library substitutes for the screen or the criteria. It also does not perform the electrocardiogram that verapamil monitoring calls for; that rhythm check remains with the prescriber. Cardiac autonomic reflex tests and heart rate variability quantify systemic autonomic regulation of the heart, a different physiological question from the cranial trigeminal-parasympathetic reflex, and a result should not be read as evidence for or against cluster headache. These measurements belong to the rest of the patient, when your own selection criteria call for an autonomic or cardiometabolic baseline. The circadian physiology behind attack timing is covered in the clock and pain, and the incentive structure that keeps fast, low-intensity care in the slow lane is taken up in the repeat-procedure pathway. Every study cited here, with its limits, is in the Chapter 11 technical companion.

Frequently asked questions

References

• Van Obberghen, E. K., Fabre, R., & Lanteri-Minet, M. (2025). Cluster headache diagnostic delay and its predictors: a systematic review with a meta-analysis. The Journal of Headache and Pain, 26(1), 71. https://doi.org/10.1186/s10194-025-02001-7
• Parakramaweera, R., Evans, R. W., Schor, L. I., Pearson, S. M., Martinez, R., Cammarata, J. S., Amin, A. J., Yoo, S. H., Zhang, W., Yan, Y., & Burish, M. J. (2021). A brief diagnostic screen for cluster headache: Creation and initial validation of the Erwin Test for Cluster Headache. Cephalalgia, 41(13), 1298–1309. https://doi.org/10.1177/03331024211018138
• Schor, L. I., Pearson, S. M., Shapiro, R. E., Zhang, W., Miao, H., & Burish, M. J. (2021). Cluster headache epidemiology including pediatric onset, sex, and ICHD criteria: Results from the International Cluster Headache Questionnaire. Headache, 61(10), 1511–1520. https://doi.org/10.1111/head.14237
• Hasirci Bayir, B. R., Nazli, E., & Ulutas, C. (2025). Cluster Headache Management: Evaluating Diagnostic and Treatment Approaches Among Family and Emergency Medicine Physicians. Medicina (Kaunas, Lithuania), 61(3), 437. https://doi.org/10.3390/medicina61030437
• Joshi, S., Rizzoli, P., & Loder, E. (2017). The comorbidity burden of patients with cluster headache: a population-based study. The Journal of Headache and Pain, 18(1), 76. https://doi.org/10.1186/s10194-017-0785-3
• Silva, L., Millner, T., Cabral, M., Costa, A., Almeida, P., Barreto, B., Pinto, M., Dias, R., Moreira, S., Bonifácio, G. V., Pinto, S. M., Castro, R., Alves, I., Rocha, A. L., Varanda, S., Costa, A., & Andrade, C. (2026). Delayed diagnosis of cluster headache in Portugal. Arquivos de Neuro-Psiquiatria, 84(9), 1–6. https://doi.org/10.1055/s-0046-1827040
• Robbins, M. S., Starling, A. J., Pringsheim, T. M., Becker, W. J., & Schwedt, T. J. (2016). Treatment of Cluster Headache: The American Headache Society Evidence-Based Guidelines. Headache, 56(7), 1093–1106. https://doi.org/10.1111/head.12866
• Choong, C. K., Ford, J. H., Nyhuis, A. W., Joshi, S. G., Robinson, R. L., Aurora, S. K., & Martinez, J. M. (2017). Clinical Characteristics and Treatment Patterns Among Patients Diagnosed With Cluster Headache in U.S. Healthcare Claims Data. Headache, 57(9), 1359–1374. https://doi.org/10.1111/head.13127
• Cohen, A. S., Matharu, M. S., & Goadsby, P. J. (2007). Electrocardiographic abnormalities in patients with cluster headache on verapamil therapy. Neurology, 69(7), 668–675. https://doi.org/10.1212/01.wnl.0000267319.18123.d3
• Fourier, C., Ran, C., Steinberg, A., Sjöstrand, C., Waldenlind, E., & Belin, A. C. (2022). Sex Differences in Clinical Features, Treatment, and Lifestyle Factors in Patients With Cluster Headache. Neurology, 100(12), e1207–e1220. https://doi.org/10.1212/WNL.0000000000201688

Related reading

• Low Back Pain Emergency Department Visits: The Primary Care Follow-Up
• Epidural Steroid Injection Overuse: Measuring the Terrain First
• Cardiac Autonomic Reflex Tests

Low Back Pain Emergency Department Visits: The Primary Care Follow-Up

Primary care follow-up after a low back pain emergency department visit should prioritize patients whose pain persists at one week, repeat presenters, patients discharged with an opioid and patients less likely to have received analgesia. The terrain primary care can measure without a procedure is fasting insulin with glucose and HbA1c, plus body composition.

The emergency department excludes the catastrophe and discharges everyone else with a location code. The follow-up visit in primary care is where mechanism and terrain can finally be documented.

Low back pain emergency department visits numbered 52.8 million in the United States between 2016 and 2022, roughly one visit in twenty, with a mean presenting pain score of 7.2. The encounter is engineered to exclude the minority with pathology requiring urgent treatment, and it does so competently. It is not engineered to identify mechanism or terrain, so the patient reaches primary care still carrying both questions.

Chapter 10 of The Pained Brain, by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD, makes the structural case in the video above. For the practice receiving the discharge summary, the useful questions are operational: which patients need more than a phone call, what to measure, and how to make it reproducible.

What does the ER do for lower back pain, and what does it leave out?

Emergency back-pain care is image-heavy and cause-light. A meta-analysis of 45 studies found imaging in 35.6 percent of emergency low back pain consultations versus 24.8 percent in primary care, with complex imaging climbing despite guideline campaigns. The two most frequent discharge codes are low back pain and dorsalgia, both anatomic descriptors. On vignettes written without red flags, 263 Swiss emergency physicians said they would recommend activity restriction in 72 and 67 percent of the two cases, against guideline advice.

None of this is a criticism of emergency medicine. The same literature shows emergency physicians rating their own pain care worse than any other specialty surveyed, with an odds ratio of 53 against pain medicine, and 96 percent of responding Canadian emergency physicians reporting no effective chronic-pain pathway from their department. The encounter lacks time and a destination. Metabolic markers are absent for the same reason: fasting insulin is not on an emergency order set for back pain, because it cannot change the disposition decision.

Which patients need follow-up after a low back pain emergency department visit?

• Pain persisting at one week. Among 354 patients from two analgesic trials, pain at the one-week call carried an odds ratio of 2.42 for functional impairment and 3.83 for moderate or severe pain at three months, while a psychosocial risk score added no independent prediction.
• Repeat presenters. In one department’s back-pain sample, 59.2 percent had presented for the same problem before. At a Canadian center, 38 percent of patients making twelve or more visits a year presented with chronic pain.
• Patients discharged with an opioid. One-year return for the same complaint ran 68 versus 55 percent, confounded by indication. Duration of the first episode tracks persistence: among 1,294,247 opioid-naive adults, 6.0 percent were still taking opioids at a year overall and 29.9 percent when the first episode lasted 31 days or more. Stewardship here means a documented duration and a review date, not abstinence.
• Patients less likely to have received analgesia. Pooled data show lower odds of any analgesic for Black patients (0.80) and older patients (0.74).

A general framework for prioritization sits under selection criteria.

The three questions, and the one primary care can measure

Dr. Padda frames persistent pain around structure, mechanism and terrain. Structure requires controlled image-guided blocks: six-month success after lumbar medial branch radiofrequency neurotomy was 26 percent when selection rested on a single block and 56 percent after two blocks with complete relief. That is a pain-medicine referral, and the rigor of the diagnostic step determines the downstream result.

Terrain is what a primary care office can quantify in the follow-up window without a procedure. Measura [Cardiometabolic and Autonomic Health Analysis] performs the measurements and reports them; interpretation and management stay with the ordering physician.

• Laboratory panels that include fasting insulin with glucose and HbA1c, capturing compensated insulin resistance that a normal glucose conceals.
• Bioimpedance body composition to separate fat and lean compartments, since BMI alone does not characterize the metabolic load.
• For older patients, a documented cognitive assessment baseline and fall-risk review belong in the same episode, filed where the next clinician will find them.

The less obvious point concerns what the system chose to measure. Across 45 studies in the meta-analysis of interventions to reduce emergency opioid prescribing, prescribing fell by 22.61 percent, yet the authors reported insufficient data on pain relief. The field measured the prescription and not the patient. Primary care is positioned to measure the patient.

What improves outcomes after an emergency visit for back pain?

Timing matters. In 265 patients receiving physical therapy after an emergency back-pain visit, starting within 30 days rather than between 31 and 90 days was associated with relative risks of 0.47 for lumbar surgery, 0.72 for advanced imaging and 0.45 for long-term opioid use; repeat emergency visits did not differ significantly. In acute sciatica, a transforaminal epidural steroid injection within eight weeks reduced leg pain modestly, and opioid use was lower in the injection arms, a bridge that spares the drug.

The nulls belong in the same paragraph. A tertiary department that added a rapid-access physiotherapy clinic to its back-pain pathway saw no significant change in admissions, partly because 41 percent of referred patients attended. An interdisciplinary program for frequent attenders improved present pain faster and reduced aberrant opioid use but did not reduce emergency visits more than usual care. Advanced-access primary care lowered emergency use in all 3 studies that measured it, none significantly. Individualized care plans for frequent users did reduce visit frequency across 13 studies. The pattern favors a same-week visit that is attended and that produces a plan, and that is precisely what patient outcomes depend on.

Workflow: standing orders and documentation

Reproducibility comes from a written protocol. A standing order can define the trigger (an emergency discharge for back pain within the prior week), a scripted one-week call on pain and function, and, where pain persists, a visit with a defined terrain measurement set. Staffing and workflow determine whether the call happens at all.

Documentation carries the rest. Structured results support HEDIS and value-based care documentation and MIPS reporting as quality concepts, and repeat measurements can be trended through chronic care and between-visit monitoring. For repeat presenters, the humility is shared: primary care is often the missing door too, and a measured plan is what turns the follow-up call into one.

Every figure above, with its design limits, is set out in the book’s chapter companion. The preceding piece in the series covers terrain screening in fibromyalgia and small-fiber pathology.

Frequently asked questions

References

• Fellner, A., & Kim, H. S. (2025). Usual Care for Low Back Pain at United States Emergency Departments, 2016-2022. Annals of Emergency Medicine, 86(6), 639–645. https://doi.org/10.1016/j.annemergmed.2025.06.005
• Downie, A., Hancock, M., Jenkins, H., Buchbinder, R., Harris, I., Underwood, M., Goergen, S., & Maher, C. G. (2020). How common is imaging for low back pain in primary and emergency care? Systematic review and meta-analysis of over 4 million imaging requests across 21 years. British Journal of Sports Medicine, 54(11), 642–651. https://doi.org/10.1136/bjsports-2018-100087
• Friedman, B. W., Conway, J., Campbell, C., Bijur, P. E., & John Gallagher, E. (2018). Pain One Week After an Emergency Department Visit for Acute Low Back Pain Is Associated With Poor Three-month Outcomes. Academic Emergency Medicine, 25(10), 1138–1145. https://doi.org/10.1111/acem.13453
• Shah, A., Hayes, C. J., & Martin, B. C. (2017). Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use – United States, 2006-2015. MMWR. Morbidity and Mortality Weekly Report, 66(10), 265–269. https://doi.org/10.15585/mmwr.mm6610a1
• Schneider, B. J., Doan, L., Maes, M. K., Martinez, K. R., Gonzalez Cota, A., & Bogduk, N. (2020). Systematic Review of the Effectiveness of Lumbar Medial Branch Thermal Radiofrequency Neurotomy, Stratified for Diagnostic Methods and Procedural Technique. Pain Medicine, 21(6), 1122–1141. https://doi.org/10.1093/pm/pnz349
• Daoust, R., Paquet, J., Marquis, M., Chauny, J. M., Williamson, D., Huard, V., Arbour, C., Émond, M., & Cournoyer, A. (2022). Evaluation of Interventions to Reduce Opioid Prescribing for Patients Discharged From the Emergency Department: A Systematic Review and Meta-analysis. JAMA Network Open, 5(1), e2143425. https://doi.org/10.1001/jamanetworkopen.2021.43425
• Magel, J., Kim, J., Fritz, J. M., & Freburger, J. K. (2020). Time Between an Emergency Department Visit and Initiation of Physical Therapist Intervention: Health Care Utilization and Costs. Physical Therapy, 100(10), 1782–1792. https://doi.org/10.1093/ptj/pzaa100
• Davidson, S. R. E., Kamper, S., Haskins, R., Petkovic, D., Feenan, N., Smith, D., O’Flynn, M., Pallas, J. D., Donald, B., Smiles, J. P., Machado, G., Oldmeadow, C., & Williams, C. M. (2026). Impact of strategies to improve flow and lower hospital admissions for low back pain in the emergency department: an interrupted time-series analysis. Emergency Medicine Journal, 43(4), 230–237. https://doi.org/10.1136/emermed-2024-214082
• Grant, K. L., McParland, A. L., Francispragasam, M., & Oxciano, P. (2023). Referral pathways for chronic pain patients from Canadian emergency departments: emergency physicians’ practices, perspectives, and recommendations. CJEM, 25(9), 761–767. https://doi.org/10.1007/s43678-023-00566-3
• Wong, C. K., O’Rielly, C. M., Teitge, B. D., Sutherland, R. L., Farquharson, S., Ghosh, M., Robertson, H. L., & Lang, E. (2020). The Characteristics and Effectiveness of Interventions for Frequent Emergency Department Utilizing Patients With Chronic Noncancer Pain: A Systematic Review. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 27(8), 742–752. https://doi.org/10.1111/acem.13934

Related reading

• Fibromyalgia and Small Fiber Neuropathy: Screening the Terrain
• Screening for Cluster Headache in Primary Care: A Three-Item Workflow
• Laboratory Panels

Fibromyalgia and Small Fiber Neuropathy: Screening the Terrain

Screen patients with fibromyalgia or chronic widespread pain for small-fiber involvement, above all to search for a treatable cause. Sudomotor testing gives a noninvasive read on small-fiber function without replacing skin biopsy, while body composition, heart rate variability and laboratory panels measure the terrain around central sensitization.

Small-fiber pathology turns up in roughly half of fibromyalgia patients, yet it does not account for their sensory findings. That paradox is the clinical case for measuring the terrain around central sensitization.

Pooled across eight studies and 222 participants, small-fiber pathology is present in 49 percent of fibromyalgia patients, and an independent meta-analysis of 903 patients reproduced the figure. The fibromyalgia small fiber neuropathy overlap is real. It is not, however, the mechanism of the pain: when 57 consecutive fibromyalgia patients were split by biopsy result, clinical measures, sensory testing and evoked potentials did not differ between the groups.

That result reframes the workup. The fiber loss behaves like residue of a chronically inflamed terrain, while the pain itself is generated upstream by central amplification. Chapter 9 of The Pained Brain, by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD, presented in the video above, lays out that mechanism. For a primary care, pain, endocrine or geriatric practice, the working questions are narrower: whom to measure, with what, and what a result changes.

How is central sensitization measured?

Woolf’s physiological definition describes a prolonged, reversible gain in excitability and synaptic efficacy within central nociceptive circuits. The bedside instruments have published reliability. In 88 participants retested by different raters, pressure pain threshold reached an ICC of 0.77 or better and temporal summation 0.76 or better; conditioned pain modulation is the noisiest of the three, with best intra-session ICCs of 0.64 in healthy subjects and 0.77 in patients. These are quantitative sensory testing protocols, usually run in pain or research settings. Measura [Cardiometabolic and Autonomic Health Analysis] does not perform them.

The questionnaire most clinics rely on is a different instrument again. Pooled across 66 studies with 13,284 participants, Central Sensitization Inventory scores correlated strongly with depression, anxiety, stress and catastrophizing and weakly or not at all with experimental nociceptive measures. It screens for a syndrome; it does not quantify gain. What an office can quantify reproducibly is the terrain tied to a lowered threshold; see the clinical rationale.

What terrain drives central sensitization?

• Visceral adiposity and leptin. In 265 people with knee pain drawn from a population cohort, those with low pressure thresholds had a median visceral fat area of 130 versus 95 square centimeters and leptin of 22.2 versus 13.3 ng/mL. Both remained associated with widespread pain in the normal-BMI subgroup, 12 percent of whom reported chronic widespread pain. CRP, fasting glucose and HbA1c were not associated.
• Cardiometabolic load before any pain. In 302 healthy adults without a pain condition, a latent load constructed from BMI, mean arterial pressure and heart-rate variability predicted greater spinal facilitation and weaker descending inhibition of the spinal reflex, after control for physical activity, sleep, stress and distress. Perceived pain sensitivity did not shift.
• Dietary pattern and systemic inflammation. Across nine knee osteoarthritis studies including 1,889 people, higher serum CRP showed indications of association with lower pressure thresholds and with temporal summation, and in 53 patients with nonspecific chronic low back pain a more pro-inflammatory dietary score tracked higher pain sensitivity.

The social driver sits beside these. Across nineteen studies, perceived stigma correlated with pain intensity, disability and depression, and family invalidation independently raised the odds of the fibromyalgia phenotype (odds ratio 1.81) with depression already in the model. The malingering base rates still in circulation derive from neuropsychologists’ impressions in forensic caseloads, and no validated method detects malingering in chronic pain. The less obvious consequence: an objective terrain finding in the problem list changes how the next clinician reads the same patient, which makes documentation a clinical intervention in its own right.

Which fibromyalgia patients should be tested for small fiber neuropathy?

Selection follows phenotype rather than a single code. Reasonable candidates include patients carrying fibromyalgia or chronic widespread pain; osteoarthritis patients whose pain has spread well beyond the affected joint, particularly before a joint-replacement referral; and patients accumulating overlapping pain diagnoses, which in 149,742 rheumatology patients applied to 22.7 percent. See the selection criteria.

• Sudomotor testing offers a noninvasive read on small-fiber sudomotor function. It does not replace skin biopsy, which remains the tissue diagnosis. The practical reason to pursue small-fiber involvement is the search for a treatable cause: in one biopsy-positive fibromyalgia series, workup identified dysimmune markers in 8 patients and hepatitis C serology in 2.
• Bioimpedance body composition separates fat and lean compartments when BMI is normal and the history is not.
• Heart rate variability and cardiac autonomic reflex tests characterize autonomic tone, one of the components of the load construct above. Pooled data also put autonomic small-fiber impairment at 45 percent in fibromyalgia.
• Laboratory panels extend beyond CRP, because the markers that tracked thresholds in the knee cohort were not the systemic inflammatory ones.

What does a terrain finding change in treatment?

Sensitization measured before treatment was associated with outcome in 17 of 25 surgical studies and in all 11 pharmacological studies of one systematic review. Knee replacement candidates with both facilitated temporal summation and impaired inhibition obtained 52.0 percent relief at one year, compared with 81.1 percent and 79.6 percent where only one measure was abnormal. The consolidating review from the same group still grades the association low to moderate and advises against routine clinical use until methods are standardized.

A terrain finding does not cancel a procedure. After discectomy for lumbar disc herniation, 100 patients improved regardless of sensitization severity. What it changes is sequencing. The metabolic plan is written before the intervention, so that the period of reduced peripheral input is used: after cervical medial branch radiofrequency neurotomy in 53 patients with chronic whiplash, widespread hyperalgesia receded within a month and returned when the nerves regenerated around ten months.

The terrain lever carries the thinnest design and the largest signal. In 110 completers of a three-month energy-restricted diet, weight fell 7.9 percent and chronic musculoskeletal pain prevalence went from 51 to 25 percent, uncontrolled, with no change in hsCRP. Serial body composition follows that change; the inflammatory marker did not. The humility belongs to interventional pain medicine: its tools were built for the joint, and in these patients the generator had moved.

Pairing with cognitive assessment and fall prevention

In 188,594 UK Biobank participants followed thirteen years, self-reported chronic widespread pain carried a hazard ratio of 2.55 for incident mild cognitive impairment and 1.53 for dementia, although the authors’ Mendelian randomization found no causal signal. That supports a documented cognitive assessment baseline in this population, repeated on the same instrument.

Fall risk enters through the pharmacology. In the Cochrane neuropathic pain pooling, gabapentin produced dizziness in 19 percent with a number needed to harm of 7.5, and pregabalin in fibromyalgia carried a number needed to harm of 3.7 for dizziness. For older patients already taking these agents, vestibular and balance testing documents the baseline the prescriber is weighing; prescribing decisions stay with the treating physician. The cognitive assessment and fall prevention page covers how the two fit together.

Documentation and workflow

Reproducibility comes from standing orders: a defined trigger such as fibromyalgia or chronic widespread pain on the problem list, a fixed measurement set, and results routed to the ordering clinician. The annual wellness visit is the natural home for the cognitive baseline and fall-risk documentation, and structured results support MIPS and quality reporting as documentation. Measura measures and reports; interpretation and management remain with the practice.

Every study cited here, with its design limits, is in the book’s chapter companion. The next piece in the series addresses the patient who arrives in primary care after an emergency visit for back pain.

Frequently asked questions

References

• Grayston, R., Czanner, G., Elhadd, K., Goebel, A., Frank, B., Üçeyler, N., Malik, R. A., & Alam, U. (2019). A systematic review and meta-analysis of the prevalence of small fiber pathology in fibromyalgia: Implications for a new paradigm in fibromyalgia etiopathogenesis. Seminars in Arthritis and Rheumatism, 48(5), 933-940 (epub 2018-08-23). https://doi.org/10.1016/j.semarthrit.2018.08.003
• Fasolino, A., Di Stefano, G., Leone, C., Galosi, E., Gioia, C., Lucchino, B., Terracciano, A., Di Franco, M., Cruccu, G., & Truini, A. (2020). Small-fibre pathology has no impact on somatosensory system function in patients with fibromyalgia. Pain, 161(10), 2385–2393. https://doi.org/10.1097/j.pain.0000000000001920
• Oaklander, A. L., Herzog, Z. D., Downs, H. M., & Klein, M. M. (2013). Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. Pain, 154(11), 2310–2316. https://doi.org/10.1016/j.pain.2013.06.001
• Adams, G. R., Gandhi, W., Harrison, R., van Reekum, C. M., Wood-Anderson, D., Gilron, I., & Salomons, T. V. (2023). Do “central sensitization” questionnaires reflect measures of nociceptive sensitization or psychological constructs? A systematic review and meta-analyses. Pain, 164(6), 1222–1239. https://doi.org/10.1097/j.pain.0000000000002830
• Andersson, M. L. E., Thorén, E., Sylwander, C., & Bergman, S. (2023). Associations between chronic widespread pain, pressure pain thresholds, leptin, and metabolic factors in individuals with knee pain. BMC Musculoskeletal Disorders, 24(1), 639. https://doi.org/10.1186/s12891-023-06773-4
• Rhudy, J. L., Kuhn, B. L., Demuth, M. J., Huber, F. A., Hellman, N., Toledo, T. A., Lannon, E. W., Palit, S., Payne, M. F., Sturycz, C. A., Kell, P. A., Guereca, Y. M., Street, E. N., & Shadlow, J. O. (2021). Are Cardiometabolic Markers of Allostatic Load Associated With Pronociceptive Processes in Native Americans?: A Structural Equation Modeling Analysis From the Oklahoma Study of Native American Pain Risk. The Journal of Pain, 22(11), 1429–1451. https://doi.org/10.1016/j.jpain.2021.04.014
• Petersen, K. K., Vaegter, H. B., Stubhaug, A., Wolff, A., Scammell, B. E., Arendt-Nielsen, L., & Larsen, D. B. (2021). The predictive value of quantitative sensory testing: a systematic review on chronic postoperative pain and the analgesic effect of pharmacological therapies in patients with chronic pain. Pain, 162(1), 31–44. https://doi.org/10.1097/j.pain.0000000000002019
• Jiang, X., Johansson, E., Nijs, J., & Wang, X. (2025). Cognitive Decline and Dementia in Chronic Widespread Pain: A Longitudinal Population-based Study. Anesthesiology, 143(6), 1560–1571. https://doi.org/10.1097/ALN.0000000000005731
• Wiffen, P. J., Derry, S., Bell, R. F., Rice, A. S. C., Tölle, T. R., Phillips, T., & Moore, R. A. (2017). Gabapentin for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews, 6(6), CD007938. https://doi.org/10.1002/14651858.CD007938.pub4
• Smith, A. D., Jull, G., Schneider, G., Frizzell, B., Hooper, R. A., & Sterling, M. (2014). Cervical radiofrequency neurotomy reduces central hyperexcitability and improves neck movement in individuals with chronic whiplash. Pain Medicine, 15(1), 128–141. https://doi.org/10.1111/pme.12262

Related reading

• HPA Axis Dysfunction in Chronic Pain: What to Measure Beyond Cortisol
• Low Back Pain Emergency Department Visits: The Primary Care Follow-Up
• Sudomotor Testing

HPA Axis Dysfunction in Chronic Pain: What to Measure Beyond Cortisol

Screen for HPA axis dysfunction in chronic pain by exposure history and downstream measures rather than a morning cortisol. Glucose, triglycerides, body composition and heart rate variability carry the signal; in one prospective study, triglycerides, waist-to-hip ratio and resting pulse predicted chronic back pain where hair cortisol did not.

In chronic pain the stress axis runs high in some patients, low in others and flat in many. The screening question is not the cortisol value but which downstream measures carry the signal.

HPA axis dysfunction is one of the most frequently invoked and least usefully measured concepts in chronic pain care. The instinct is to order a morning cortisol. The evidence says that value will rarely answer the clinical question, because in pain populations the axis is dysregulated in both directions, and what it does downstream is easier to document than the hormone itself.

The source is Chapter 8 of The Pained Brain by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD, and the chapter video above.

Can a cortisol test diagnose HPA axis dysfunction?

The most cited prospective study tested the axis in 267 psychologically at-risk adults without chronic widespread pain. Failure to suppress after dexamethasone carried an odds ratio of 3.53 for incident pain, and all three abnormalities together 8.5, but the base was 28 incident cases, and low morning saliva alone was not significant. A larger Dutch cohort of 2,039 adults followed six years found that no HPA measure predicted onset; the count of adverse life events did, at 1.14 per event.

In established pain the picture is bidirectional. Among 4,560 older English adults, chronic pain was associated with hair cortisol 15 percent higher at the low tail of the distribution and 19 percent higher near the top, with no difference in between. In 99 fibromyalgia patients, perceived stress was markedly higher than in controls while neither salivary nor hair cortisol differed. What does track outcomes is the diurnal slope: across 80 studies and 36,823 participants, a flatter slope was associated with poorer health, most strongly immune and inflammatory outcomes, and with mortality at a hazard of 2.40, or 1.63 after two outliers were removed, with evidence of publication bias.

The most instructive null came from 140 young adults with intermittent back pain. Hair cortisol was not selected as a predictor of chronic low back pain at one year. The markers that were selected were norepinephrine, interleukin-6, triglycerides, waist-to-hip ratio and resting pulse, with a development AUC of 0.93 falling to 0.88 after bootstrapping and no external validation. The stress system was visible in metabolic and autonomic variables. The hormone concentration was not.

Can cortisol be normal when the stress axis is not?

Receptor-level resistance explains part of the gap. In 33 caregivers of family members with glioblastoma, monocytes showed 1.65-fold greater NF-κB binding-motif prevalence and 0.68-fold lower glucocorticoid receptor motif prevalence, with diurnal cortisol and receptor protein similar to controls. The same study found no group difference in functional sensitivity once normalized, so this is transcriptional rather than demonstrated functional resistance. The practical point is that a reassuring cortisol value can coexist with an inflammatory phenotype.

Which life exposures point to HPA axis dysfunction?

Exposure history identifies risk better than a hormone draw, and almost none of it is on a standard intake form. Reasonable criteria in a pain or primary care population include:

• Adverse childhood experience: across 85 studies and 826,452 adults the adjusted odds of adult chronic pain were 1.45, graded from 1.29 for one experience to 1.95 for four or more, although most included studies were cross-sectional.
• Sustained financial hardship: hardship at 43 predicted chronic widespread pain at 68 with a relative risk of 4.44 in the most hard-pressed group, adjusted for measured body mass and psychiatric caseness.
• High perceived occupational stress: among 715 healthcare workers without baseline back pain, high stress carried an odds ratio of 2.67 for low back pain a year later.
• Loneliness rather than living alone: in 315,197 UK Biobank participants, loneliness carried a hazard of 1.32 for low back pain after broad adjustment, while objective isolation raised nothing.
• Caregiving and job strain, which also carry metabolic risk: job strain raised the hazard of type 2 diabetes 1.15-fold across 124,808 adults, and three or more work-stress exposures carried 2.25 times the odds of the metabolic syndrome among 10,308 civil servants.

These map onto the practice criteria in selection criteria for testing. The ten-item Perceived Stress Scale, banded 0-9 low, 10-19 moderate and 20-40 high in the prospective work, is a reasonable repeated documentation field alongside them.

What should be measured instead of cortisol?

The downstream record is where Measura [Cardiometabolic and Autonomic Health Analysis] fits. It is a measurement protocol reported to the ordering physician, not a diagnostic or treatment service in its own right.

• Laboratory panels for glucose, triglycerides and related metabolic markers, the variables that carried prospective signal where cortisol did not.
• Bioimpedance body composition to document fat and lean compartments, since waist circumference in the hair-cortisol cohorts is a proxy rather than a measure of visceral fat.
• Heart rate variability as an autonomic baseline. Across 52 studies of chronic primary pain, higher baseline cortisol accompanied lower recovery heart rate variability, at very low to moderate certainty.
• Cardiac autonomic reflex tests where symptoms suggest broader autonomic involvement beyond resting variability.
• A cognitive assessment baseline in older patients, given the imaging association between higher cortisol and smaller hippocampal volume in chronic back pain.

Trapezius pressure-pain algometry, which tracked perceived stress in 2,199 adults, is a clinic test outside this library.

What a finding changes

A documented pattern moves stress from a dismissal to a treatment target, and the sober effect sizes belong in the conversation. In 342 adults with chronic low back pain, mindfulness-based stress reduction produced meaningful functional improvement in 60.5 percent at 26 weeks, cognitive behavioral therapy in 57.7 percent and usual care in 44.1 percent. Pain reprocessing therapy left 66 percent of 151 adults with mild to moderate back pain at or near zero pain against 20 percent with placebo injection. Against an active control, the Cochrane estimate for cognitive behavioral therapy on pain intensity was only 0.09, which argues for setting expectations around function and distress. In 73 adults with PTSD and chronic pain, heart rate variability biofeedback cut pain interference 24.9 percent without a between-group difference in intensity, a direct reason to repeat the autonomic measure.

Interventional care belongs in the same plan. Of 14 back pain patients rescanned six months after spine surgery or facet injection, left dorsolateral prefrontal thickness had recovered in step with falling pain and disability. Quieting the signal buys the window for retraining the axis; repeat measures show whether the terrain moved.

Documentation and workflow

Dr. Padda’s position is that the profession has to stop charting stress as a verdict: in a survey of people with chronic pain, 77 percent described provider invalidation, which was associated with poorer physical function. Writing the mechanism into the record, with exposures and measures attached, is the correction. A standing order triggered by a documented exposure plus a pain diagnosis makes the workup reproducible; see standing orders for screening. The annual wellness visit is the natural repeat point, covered in annual wellness visit integration, and the same cardiometabolic documentation supports MIPS and HEDIS quality concepts. Unmeasured is unmanaged. Study-level detail is in the Chapter 8 companion supplement, the sleep side of the same clock is sleep deprivation and insulin resistance screening, and a patient-facing version is available for handouts.

Frequently asked questions

References

• McBeth, J., Silman, A. J., Gupta, A., Chiu, Y. H., Ray, D., Morriss, R., Dickens, C., King, Y., & Macfarlane, G. J. (2007). Moderation of psychosocial risk factors through dysfunction of the hypothalamic-pituitary-adrenal stress axis in the onset of chronic widespread musculoskeletal pain: findings of a population-based prospective cohort study.
• Generaal, E., Vogelzangs, N., Macfarlane, G. J., Geenen, R., Smit, J. H., de Geus, E. J., Penninx, B. W., & Dekker, J. (2015). Biological stress systems, adverse life events and the onset of chronic multisite musculoskeletal pain: a 6-year cohort study.
• Adam, E. K., Quinn, M. E., Tavernier, R., McQuillan, M. T., Dahlke, K. A., & Gilbert, K. E. (2017). Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysis.
• Miller, G. E., Murphy, M. L. M., Cashman, R., Ma, R., Ma, J., Arevalo, J. M. G., Kobor, M. S., & Cole, S. W. (2014). Greater inflammatory activity and blunted glucocorticoid signaling in monocytes of chronically stressed caregivers.
• Bussières, A., Hancock, M. J., Elklit, A., Ferreira, M. L., Ferreira, P. H., Stone, L. S., Wideman, T. H., Boruff, J. T., Al Zoubi, F., Chaudhry, F., Tolentino, R., & Hartvigsen, J. (2023). Adverse childhood experience is associated with an increased risk of reporting chronic pain in adulthood: a stystematic review and meta-analysis.
• Ma, X., Song, X., Zou, Y., Zhang, D., Yang, B., Lei, B., Zhou, J., Zhao, X., Xiang, R., Qu, Y., Zheng, S., Yu, T., Han, T., Zhong, Y., Xia, M., Fan, M., Jiang, X., & Zhang, B. (2026). Loneliness, traditional risk factor control, genetic predisposition, and development of musculoskeletal disorders.
• Vyverman, J., De Baere, R., Timmers, I., Coppieters, I., Van Oosterwijck, J., & Moerkerke, M. (2026). The stress-pain connection in chronic primary pain: A systematic review and meta-analysis of physiological stress markers in relation to experimental pain responses.
• Cherkin, D. C., Sherman, K. J., Balderson, B. H., Cook, A. J., Anderson, M. L., Hawkes, R. J., Hansen, K. E., & Turner, J. A. (2016). Effect of Mindfulness-Based Stress Reduction vs Cognitive Behavioral Therapy or Usual Care on Back Pain and Functional Limitations in Adults With Chronic Low Back Pain: A Randomized Clinical Trial.
• Williams, A. C. de C., Fisher, E., Hearn, L., & Eccleston, C. (2020). Psychological therapies for the management of chronic pain (excluding headache) in adults.
• Seminowicz, D. A., Wideman, T. H., Naso, L., Hatami-Khoroushahi, Z., Fallatah, S., Ware, M. A., Jarzem, P., Bushnell, M. C., Shir, Y., Ouellet, J. A., & Stone, L. S. (2011). Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function.

Related reading

• Sleep Deprivation and Insulin Resistance: Who to Screen in Pain Care
• Fibromyalgia and Small Fiber Neuropathy: Screening the Terrain
• Laboratory Panels

Sleep Deprivation and Insulin Resistance: Who to Screen in Pain Care

Screen for insulin resistance in chronic pain patients who report insomnia, frequent night waking or poor sleep quality, work night or rotating shifts, or take a nightly opioid. Fasting glucose and HbA1c alone miss the compensated phase, so the workup adds fasting insulin and triglycerides.

Four nights of restricted sleep measurably lower insulin sensitivity in healthy adults. In a pain population that sleeps in fragments, that makes the sleep history a metabolic screening trigger, not a lifestyle note.

The evidence on sleep deprivation insulin resistance is no longer epidemiology alone. Hyperinsulinemic clamp studies in healthy adults show whole-body insulin sensitivity falling within four to five nights of restriction, and the fall is larger when the sleep is also mistimed. For a physician managing chronic pain, the implication is operational: a patient who reports broken sleep is carrying a metabolic exposure that the usual fasting glucose will detect late, if at all.

The clinical argument comes from The Pained Brain by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD, in the chapter whose video is titled Why Pain Is Worst at 3 a.m. What follows translates it into screening terms: the effect sizes worth knowing, who meets a reasonable threshold for testing, what a result changes, and how to make it reproducible in a busy practice.

How much does sleep loss lower insulin sensitivity?

Magnitudes first. In 14 healthy adults, five nights of 4 hours against 8 lowered whole-body insulin sensitivity 25 percent and peripheral sensitivity 29 percent, with 24-hour urinary cortisol up 21 percent. In postmenopausal women, four nights of restriction cut clamp sensitivity 20 percent at the low insulin dose. Adipocytes biopsied from seven lean young adults after four nights at 4.5 hours needed nearly three times the insulin for half-maximal signaling, a 30 percent drop in total signaling response against a 16 percent drop in whole-body sensitivity. Pooled across 41 randomized trials of sleep restriction, the standardized effect on insulin sensitivity was -0.70.

Timing is a separate insult. Held to identical short sleep, men whose sleep was also shifted lost 58 percent of insulin sensitivity against 32 percent when aligned, and hsCRP rose 146 percent against 64. With the whole day moved 12 hours out of phase, glucose rose only 6 percent despite 22 percent more insulin, and 3 of 8 participants reached a prediabetic postprandial range. That compensation is the screening problem in miniature.

These are small samples of healthy volunteers over days, and the misalignment effect was significant in men only. None enrolled chronic pain patients. What they establish is mechanism and direction, and the population data supply the rest: each hour of sleep below seven carried 1.09 times the risk of type 2 diabetes across 482,502 participants, and night-shift work carried 1.30 times the hazard across ten cohorts.

Sleep deprivation insulin resistance: who meets the threshold for testing

Sleep disturbance and chronic musculoskeletal pain predict each other. In a 20-cohort meta-analysis of 208,190 adults, baseline sleep problems predicted incident pain at an odds ratio of 1.79, and baseline pain predicted incident sleep problems at 2.02. In daily reporting over six months in 801 adults, the sleep-to-pain path was the stronger one, and quality rather than duration carried it. Reasonable selection criteria include:

• Chronic pain with insomnia, frequent nocturnal awakening or self-reported poor sleep quality.
• Night-shift or rotating work, noting that the pooled diabetes association was significant in women and not in men, and that nurses showed no significant pain association once pooled.
• Nightly opioid therapy: central sleep apnea affects about 24 percent of chronic opioid users, and in a multi-clinic cohort 58.8 percent of opioid-treated pain patients who completed a sleep study had sleep apnea, of whom only a quarter of the newly diagnosed received treatment.
• Sedative-hypnotic use in older adults, for reasons covered under falls below.
• Reported loss of strength or muscle, given that sarcopenia carried 1.26 times the odds of chronic pain in pooled adjusted data.

The social determinants are part of the selection, not an afterthought. Shift rosters, lit bedrooms and irregular schedules are occupational and economic exposures before they are behaviors. The practice-level criteria in selection criteria for testing map onto these groups directly.

What changes in management when sleep loss is found?

The first change is what gets measured. Fasting glucose and HbA1c alone will miss the compensated phase that the misalignment data describe, so a metabolic workup in this group reasonably adds fasting insulin and triglycerides through laboratory panels. Bioimpedance body composition documents lean and fat mass, which matters because overweight adults dieting on 5.5 hours of sleep lost 60 percent more lean mass than on 8.5, and because the NHANES analysis linking 10 percent more muscle to 11 percent lower HOMA-IR estimated muscle by impedance. Heart rate variability gives an autonomic baseline in a population in which six nights of restriction raised sympathetic activity.

The second change is sequencing. The practice position in the source material is that the sleep history is taken with the pain history, an apnea screen precedes the first opioid prescription, and a sleep study precedes dose escalation. That is a practice-reported position from our own population, not a trial outcome, and individual results vary. Polysomnography is outside the Measura [Cardiometabolic and Autonomic Health Analysis] library and is ordered separately; the value of pairing it with metabolic testing is that the same patient’s apnea, insulin and body composition are documented together rather than in three silos.

The third change is expectation setting. Cognitive behavioral therapy for insomnia produced a standardized 0.89 improvement in sleep and only 0.20 in pain across 12 trials, yet roughly a third of fibromyalgia patients achieved more than 30 percent pain reduction, and only the sleep-treated group held it at six months. Repeat metabolic measurement is how a clinician sees whether the terrain moved even when the pain score has not.

Pairing with fall prevention and cognitive assessment

The patients most likely to be sleeping badly on medication are also the patients at fall risk. Z-drug users carried 1.63 times the odds of fracture across 14 studies, and hip fracture risk ran roughly 2.4-fold for new users of both benzodiazepines and Z-drugs. Vestibular and balance testing belongs in the same encounter for older adults on sedative-hypnotics, and a cognitive assessment baseline gives the prescriber something to compare against when sedating regimens are reviewed. The integration model is laid out in cognitive assessment and fall prevention.

Documentation and workflow

Screening only works when it is reproducible. A standing order that fires on a documented sleep complaint in a chronic pain patient removes the dependence on one clinician remembering to ask; the template is in standing orders for screening. Record sleep as two fields, hours and awakenings, because fragmentation removed endogenous pain inhibition at matched sleep loss while consolidated restriction did not. Results belong in the structured record, and the annual wellness visit is a natural point to repeat the panel; see annual wellness visit integration. Where fall risk screening and cardiometabolic measures are tracked for MIPS or HEDIS, the same documentation supports those quality concepts without a separate workflow.

Dr. Padda directs the sharpest criticism at his own specialty: prescribing for pain while ignoring the clock was, in his words, a failure of care. The corrective is not a lecture on sleep hygiene. It is a measured baseline and a scheduled repeat. Unmeasured is unmanaged. The primary studies and their design limits are collected in the Chapter 7 companion supplement, the stress-axis companion is HPA axis dysfunction as a screening problem, and a patient-facing version is available to share.

Frequently asked questions

References

• Rao, M. N., Neylan, T. C., Grunfeld, C., Mulligan, K., Schambelan, M., & Schwarz, J.-M. (2015). Subchronic sleep restriction causes tissue-specific insulin resistance.
• Broussard, J. L., Ehrmann, D. A., Van Cauter, E., Tasali, E., & Brady, M. J. (2012). Impaired insulin signaling in human adipocytes after experimental sleep restriction: a randomized, crossover study.
• Zhu, B., Shi, C., Park, C. G., Zhao, X., & Reutrakul, S. (2019). Effects of sleep restriction on metabolism-related parameters in healthy adults: A comprehensive review and meta-analysis of randomized controlled trials.
• Leproult, R., Holmbäck, U., & Van Cauter, E. (2014). Circadian misalignment augments markers of insulin resistance and inflammation, independently of sleep loss.
• Santos, M., Gabani, F. L., de Andrade, S. M., Bizzozero-Peroni, B., Martínez-Vizcaíno, V., González, A. D., & Mesas, A. E. (2023). The bidirectional association between chronic musculoskeletal pain and sleep-related problems: a systematic review and meta-analysis.
• Xie, F., Hu, K., Fu, R., Zhang, Y., Xiao, K., & Tu, J. (2024). Association between night shift work and the risk of type 2 diabetes mellitus: a cohort-based meta-analysis.
• Wasef, S., Mir, S., Ryan, C., Waseem, R., Bellingham, G., Kashgari, A., Wong, J., & Chung, F. (2021). Treatment for patients with sleep apnea on opioids for chronic pain: results of the OpSafe trial.
• Nedeltcheva, A. V., Kilkus, J. M., Imperial, J., Schoeller, D. A., & Penev, P. D. (2010). Insufficient sleep undermines dietary efforts to reduce adiposity.
• Donnelly, K., Bracchi, R., Hewitt, J., Routledge, P. A., & Carter, B. (2017). Benzodiazepines, Z-drugs and the risk of hip fracture: A systematic review and meta-analysis.
• Selvanathan, J., Pham, C., Nagappa, M., Peng, P. W. H., Englesakis, M., Espie, C. A., Morin, C. M., & Chung, F. (2021). Cognitive behavioral therapy for insomnia in patients with chronic pain – A systematic review and meta-analysis of randomized controlled trials.

Related reading

• Carpal Tunnel and Diabetes: Hand Diagnoses as Screening Triggers
• HPA Axis Dysfunction in Chronic Pain: What to Measure Beyond Cortisol
• Laboratory Panels

Carpal Tunnel and Diabetes: Hand Diagnoses as Screening Triggers

Carpal tunnel syndrome is a diabetes screening trigger: across more than 37 million people, diabetes carried adjusted odds of 1.69 for it. Test any patient with carpal tunnel, trigger finger, Dupuytren’s contracture, frozen shoulder or tendinopathy, with a lower threshold when two coexist or carpal tunnel appears under age 40.

Entrapments and capsular stiffness cluster in dysglycemia, and genetic data now place glycemia upstream. That makes the hand and shoulder visit a screening point most practices let pass.

Carpal tunnel and diabetes are usually documented in different parts of the chart by different clinicians, which is how the carpal tunnel diabetes link goes unread. The hand surgeon releases the ligament, the endocrinologist does not see the patient until the A1c crosses a line, and the problem list accumulates musculoskeletal diagnoses that nobody reads as a glycemic signal. The video above is Chapter 6 of The Pained Brain by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD, which traces advanced glycation end products into tendon, capsule and nerve tunnel. The screening questions are who to test when one of these diagnoses appears, what to measure, and what a result changes before the next injection or release.

How strongly is carpal tunnel linked to diabetes?

Pooling 25 studies and 92,564 individuals, diabetes carried unadjusted odds of 1.97 for carpal tunnel syndrome or release, and adjusted odds of 1.69 across 18 studies covering more than 37 million people, with no difference between type 1 and type 2. A 2026 propensity-matched analysis of roughly 6.5 million insured US adults gave hazards of 1.35 for incident carpal tunnel and 1.28 for tarsal tunnel, rising to 1.68 for carpal tunnel under age 40. Adhesive capsulitis is five times more likely in diabetes, with a prevalence of 13.4 percent, and 30 percent of patients presenting with it have diabetes.

The digital diagnoses cluster as well. Comparing 2,250 patients with coded trigger finger against 398,495 without, trigger finger carried odds of 9.59 for coexisting carpal tunnel and 4.89 for Dupuytren’s. Dupuytren’s prevalence runs 31 percent with diabetes versus 14 percent without.

Does high blood sugar come before carpal tunnel?

Observational pooling cannot establish direction; Mendelian randomization goes further. Using variants that set lifelong HbA1c in about 379,700 unrelated Europeans, each 10 mmol/mol of genetically predicted A1c carried odds of 1.20 for carpal tunnel, 1.30 for trigger finger, 1.17 for Dupuytren’s and 1.50 for frozen shoulder. In 139 carriers of pathogenic GCK mutations, who live with mildly raised fasting glucose from birth, carpal tunnel odds were 2.86 and frozen shoulder odds 7.16. Limits: European ancestry, healthy-volunteer bias, and no ability to say whether lowering glucose now reverses risk. The direction of cause, though, is no longer the open question.

Can a normal A1c rule out diabetic changes in the hand?

For years I read prediabetic A1c values as reassurance. The musculoskeletal data are a large part of why I stopped, and they expose a second-order screening problem. In 100 adults with prediabetes against 50 controls, hand function was worse and limited joint mobility more prevalent, associated with carpal tunnel and trigger finger, yet A1c, fasting glucose and two-hour glucose showed no relationship to hand function. In 158 adults without diabetes or metabolic syndrome, matched on sex, age, body mass and activity, those at a mean A1c of 40.28 versus 34.34 mmol/mol had poorer Achilles collagen quality on MRI and slower gait. In controlled type 2 diabetes, Achilles stiffness ran 8.3 against 5.6 Nm/mm with stiffness tracking A1c, yet without a difference in measured serum or skin AGE.

Skin autofluorescence is often proposed as the shortcut. It is a separate optical test that Measura [Cardiometabolic and Autonomic Health Analysis] does not perform, and in 4,181 primary-care recruits it performed poorly as a prediabetes screen, with an area under the curve of 0.52. The consequence is that a glycemic number identifies exposure but does not tell you whose collagen, nerve or muscle has already changed. Functional measurement is what separates those patients.

Carpal tunnel diabetes screening: who to test and what to measure

• Any patient with carpal tunnel syndrome, trigger finger, Dupuytren’s contracture, adhesive capsulitis or tendinopathy, with a lower threshold when two coexist or when carpal tunnel appears under age 40.
• Patients scheduled for intra-articular steroid, rotator cuff repair, carpal tunnel release or knee arthroplasty whose glycemic and insulin status is undocumented.
• Patients whose A1c carries a prediabetes label that never generated further workup.

Laboratory panels establish A1c and fasting insulin together. Sudomotor testing assesses sweat-gland function supplied by small nerve fibers in the hands and feet; it does not diagnose an entrapment, but it addresses the diffuse small-fiber question in a population where, among 62 people with type 2 diabetes, skin AGE burden tracked reduced sciatic nerve structural integrity. Bioimpedance body composition quantifies lean and fat compartments, and vestibular and balance testing documents postural stability. Results return to the treating physician and inform care; they do not replace electrodiagnostic or surgical evaluation.

What changes before an injection or carpal tunnel surgery?

The most immediate change is procedural planning. A single 40-milligram triamcinolone injection in 33 patients with knee osteoarthritis and type 2 diabetes raised mean daily glucose from 161.7 to 198.8 mg/dL over days one to three, with 49.9 percent of hours above 180; across seven published series every study showed a rise, some peaking near 500, most within 24 to 72 hours. Rotator cuff retear ran 28.2 percent in diabetes against 19.3 percent, and 40.0 percent at an A1c of 7.0 or above against 14.6 percent in non-diabetics, although that subgroup rests on two studies. After carpal tunnel release, symptom scores matched, but wrist-to-palm sensory conduction improved 4.31 m/s less in diabetics.

None of this argues against the procedure; a compressed nerve needs decompression. It argues for injections as a bridge, the fewest that keep the patient functional, with glucose and insulin known in advance, and for coordinated glycemic management around surgery. No agent has dissolved a glucosepane cross-link in a living person: pimagedine missed its primary endpoint and alagebrium did not lower the skin reading. What has been shown is slower, less accumulation in skin collagen years later among type 1 patients randomized to intensive control. On the dietary side, a year of low-AGE eating took HOMA-IR from 3.1 to 1.9 in 138 obese adults with metabolic syndrome, and 13 randomized trials pooled to a HOMA-IR reduction of 1.204; no trial has yet tested that diet against a pain endpoint.

Pairing with fall prevention

Glycation is a musculoskeletal problem beyond the hand. In 2,744 adults with a mean age of 74, each unit of skin autofluorescence carried odds of 2.01 for confirmed sarcopenia, with lower appendicular lean mass, weaker grip and slower gait. Observational, but it places the diabetic hand in the same patient as the future fall. A practice already running cognitive assessment and fall prevention can add body composition and balance measurement to that visit rather than ordering them after an injury.

Workflow and documentation

These diagnoses are already coded, which makes them usable triggers. A standing order that fires on a new entrapment, trigger digit or adhesive capsulitis diagnosis removes dependence on individual recall. The annual wellness visit is the natural place to reconcile a problem list full of musculoskeletal diagnoses with a glycemic workup that never happened. The patient version of this evidence is frozen shoulder and diabetes: the numbers worth checking; the study-level appraisal is on the Chapter 6 book companion page; and the omega-6 argument that precedes it is in screening chronic NSAID users.

Frequently asked questions

References

• Pourmemari, M. H., & Shiri, R. (2016). Diabetes as a risk factor for carpal tunnel syndrome: a systematic review and meta-analysis. Diabetic Medicine, 33(1), 10-16. https://doi.org/10.1111/dme.12855
• Rydberg, M., Lakhlani, D., Sutjiadi, B. J., Fox, P. M., & Curtin, C. (2026). Diabetes and the risk of entrapment neuropathies of the upper and lower extremity – A propensity score-matched cohort study. Journal of Diabetes and Its Complications, 40(8), 109364. https://doi.org/10.1016/j.jdiacomp.2026.109364
• Green, H. D., Burden, E., Chen, J., Evans, J., Patel, K., Wood, A. R., Beaumont, R. N., Tyrrell, J., Frayling, T. M., Hattersley, A. T., Oram, R. A., Bowden, J., Barroso, I., Smith, C., & Weedon, M. N. (2024). Hyperglycaemia is a causal risk factor for upper limb pathologies. International Journal of Epidemiology, 53(1), dyad187. https://doi.org/10.1093/ije/dyad187
• Guggenheim, L., Kang, Y., Furniss, D., & Wiberg, A. (2024). Identifying non-genetic factors associated with trigger finger. Journal of Plastic, Reconstructive & Aesthetic Surgery, 94, 91-97. https://doi.org/10.1016/j.bjps.2024.04.066
• Erol, K., Akyıldız Tezcan, E., Topaloğlu, U. S., & Göl, M. F. (2025). Diabetic Hand Complications in Prediabetes: A Controlled Observational Study. Archives of Physical Medicine and Rehabilitation, 107(5), 868-874. https://doi.org/10.1016/j.apmr.2025.07.006
• Magris, R., Monte, A., Vigolo, N., Nardello, F., Trinchi, M., Negri, C., Gisondi, P., Cosma, C., Sartore, G., Lapolla, A., Moghetti, P., & Zamparo, P. (2026). Impact of controlled type 2 diabetes on muscle-tendon mechanics. Acta Diabetologica, 63(7), 1239-1246. https://doi.org/10.1007/s00592-026-02705-5
• Sánchez, E., Kerkeni, M., Hernández, M., Gavaldà, R., Rius, F., Sauret, A., Torres, G., Bermúdez-López, M., Fernández, E., Castro-Boqué, E., Purroy, F., Mauricio, D., Farràs-Sallés, C., Buti, M., Godoy, P., Pamplona, R., & Lecube, A. (2022). Weak Association between Skin Autofluorescence Levels and Prediabetes with an ILERVAS Cross-Sectional Study. Nutrients, 14(5), 1102. https://doi.org/10.3390/nu14051102
• Russell, S. J., Sala, R., Conaghan, P. G., Habib, G., Vo, Q., Manning, R., Kivitz, A., Davis, Y., Lufkin, J., Johnson, J. R., Kelley, S., & Bodick, N. (2018). Triamcinolone acetonide extended-release in patients with osteoarthritis and type 2 diabetes: a randomized, phase 2 study. Rheumatology (Oxford, England), 57(12), 2235-2241. https://doi.org/10.1093/rheumatology/key265
• Yang, L., Zhang, J., Ruan, D., Zhao, K., Chen, X., & Shen, W. (2020). Clinical and Structural Outcomes After Rotator Cuff Repair in Patients With Diabetes: A Meta-analysis. Orthopaedic journal of sports medicine, 8(9), 2325967120948499. https://doi.org/10.1177/2325967120948499
• Waqas, K., Chen, J., Trajanoska, K., Ikram, M. A., Uitterlinden, A. G., Rivadeneira, F., & Zillikens, M. C. (2022). Skin Autofluorescence, a Noninvasive Biomarker for Advanced Glycation End-products, Is Associated With Sarcopenia. The Journal of Clinical Endocrinology and Metabolism, 107(2), e793–e803. https://doi.org/10.1210/clinem/dgab632

Related reading

• NSAID Cardiovascular Risk in Chronic Pain: Who to Measure and Why
• Sleep Deprivation and Insulin Resistance: Who to Screen in Pain Care
• Laboratory Panels

NSAID Cardiovascular Risk in Chronic Pain: Who to Measure and Why

Measure daily or near-daily NSAID users with chronic pain, especially those with diabetes, hypertension, kidney disease or a metabolic phenotype. Pooled trials put major vascular events up with coxibs and diclofenac, heart failure risk roughly doubled across the class, and chronic use carried a 1.50 hazard for chronic kidney disease.

Chronic NSAID users are an identifiable population carrying measurable vascular and renal exposure, and most of them are never assessed for it.

NSAID cardiovascular risk is well characterized in trials and seldom measured in the individual taking the drug. The daily ibuprofen or naproxen user with chronic musculoskeletal pain appears on a medication list, receives a renewal, and rarely receives a vascular, renal or metabolic assessment tied to that exposure. The video above is Chapter 5 of The Pained Brain by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD, which argues that the prostaglandin pathway these drugs block is supplied by the omega-6 content of the diet. For a screening practice, that argument reduces to two questions: which chronic users should be measured, and what a finding changes.

How much do NSAIDs raise cardiovascular risk?

The Coxib and traditional NSAID Trialists’ Collaboration pooled individual data from 280 placebo-controlled trials and 124,513 participants. Major vascular events rose with coxibs (RR 1.37) and diclofenac (RR 1.41), roughly three additional events per 1,000 patients treated for a year, one of them fatal. Naproxen was the vascular exception (RR 0.93). Heart failure risk roughly doubled across the class, and upper gastrointestinal complications rose 3.97-fold on ibuprofen and 4.22-fold on naproxen. Those trials used high doses in selected, often high-risk populations.

The signal is not confined to long courses. A Bayesian individual-patient meta-analysis of 446,763 people found odds ratios for acute myocardial infarction of 1.48 for ibuprofen, 1.50 for diclofenac and 1.53 for naproxen within one to seven days of use, dose-related and front-loaded rather than accumulating with duration. On the renal side, 40 studies covering 1,757,118 participants gave chronic use a pooled hazard of 1.50 for chronic kidney disease, 1.67 with pre-existing kidney disease and 1.35 in diabetes or hypertension. Confounding by indication is plausible in both datasets; it does not erase them.

Patient behavior widens the gap between label and exposure. In a one-week diary study of 1,326 American ibuprofen users, 37 percent also took a non-ibuprofen NSAID and 11 percent exceeded the daily ibuprofen limit, with ongoing pain among the associated characteristics.

How much do NSAIDs actually help spinal pain?

Most of us, myself included, were trained to renew the anti-inflammatory and treat the diet as somebody else’s department. The efficacy data in spinal pain do not support that reflex. Across 35 placebo-controlled trials, only 3 of 14 comparisons cleared a ten-point minimum worthwhile difference, the number needed to treat was 6, and gastrointestinal adverse events were already 2.5 times as common in trials with a median duration of 7 days. The authors concluded that no simple analgesic gives clinically important relief for spinal pain, not that NSAIDs are useless. For the physician deciding whether to measure, the relevant point is that the risk-benefit balance in long-term users is close enough for patient-level data to carry real weight.

Is a normal CRP enough to clear a chronic pain patient?

A common shortcut is to check C-reactive protein and move on. The evidence behind that shortcut was generated in the wrong population. The founding systematic review of dietary linoleic acid and inflammatory markers covered 15 randomized trials in healthy adults. A later pooling of 30 trials and 1,377 participants found a CRP effect of SMD 0.09, indistinguishable from zero, with a subgroup hint of a rise at the largest intake increases. Obese, insulin-resistant and chronic pain patients were largely absent.

In a crossover of 39 abdominally obese adults given seven weeks of marine omega-3 and seven of linoleic acid, circulating markers did not differ between treatments, yet adipose biopsies showed 334 differentially expressed genes after the omega-6 period, with inflammatory pathways up-regulated. Red-cell composition tells a parallel story: in 605 adults with chronic pain conditions, a higher arachidonic acid to EPA-plus-DHA ratio tracked higher pain intensity, cross-sectionally. The practical inference is that a normal CRP in a metabolically burdened pain patient does not clear the terrain. The population baseline is poor: 97.6 percent of US adults have a red-cell omega-3 index below 8 percent, and under 12.2 percent of US adults were metabolically healthy on NHANES 2009–2016, under 7 percent on the tighter post-2021 criteria.

Who to measure

A workable selection rule for primary care, pain, cardiology or geriatric practice starts from the medication list rather than from symptoms:

• Daily or near-daily NSAID use beyond a short course, prescribed or over the counter.
• Chronic NSAID use with diabetes, hypertension or known kidney disease, the subgroups carrying the higher renal hazards.
• Chronic pain with a metabolic phenotype: central adiposity, dysglycemia, or the thin-outside, inflamed-inside pattern that body weight conceals.
• Long-term use of the same agent without a documented reassessment.

Arterial stiffness and endothelial function assesses large-artery rigidity and the vessel lining’s capacity to dilate. Its relevance here is supported indirectly, including a cross-sectional association in 346 nonsmokers between a urinary acrolein metabolite, a product of heated polyunsaturated oil among other sources, and worse endothelial function. Laboratory panels define glycemic and insulin status alongside the renal markers the prescriber already follows. Bioimpedance body composition separates the lean and fat compartments that BMI conflates. Measura [Cardiometabolic and Autonomic Health Analysis] returns findings to the ordering physician; it does not diagnose disease on its own or manage the medication.

What a finding changes

An abnormal vascular or metabolic result does not dictate a prescribing decision. It improves the one the treating physician makes: the risk side of the NSAID discussion gains an individual measurement instead of a population estimate, the decision about agent, dose and duration becomes documented, and patients whose kidney function deserves closer follow-up are flagged. It also opens the upstream conversation Chapter 5 is really about, correcting the lipid profile. In the book’s protocol that means measuring the red-cell omega-3 index against a target above 8 percent, removing seed oils, adding EPA and DHA, and retesting at about five months, since red-cell content took roughly that long to equilibrate in a dose-response trial of 115 healthy adults. Food-based trials support the direction: in 182 adults with migraine, a high omega-3, low omega-6 diet produced 4.0 fewer headache days a month than control, although the primary quality-of-life endpoint did not reach significance.

Building it into workflow

The trigger already sits in the record. A standing order keyed to chronic NSAID use on the medication list makes the screen reproducible rather than dependent on who is in clinic that day. The annual wellness visit medication review is a natural place for it to fire. Results belong in structured fields the next prescriber will see, which getting results into the record covers, and where a practice reports cardiovascular or diabetes-related quality measures, the same data support documentation under MIPS and quality reporting. The patient-facing account of the same evidence is the patient article on seed oils and inflammation; the study-by-study appraisal is on the Chapter 5 book companion page; and the glycation problem that follows is in hand and shoulder diagnoses as dysglycemia screening triggers.

Frequently asked questions

References

• Coxib and traditional NSAID Trialists’ (CNT) Collaboration (2013). Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. The Lancet, 382(9894), 769-779. https://doi.org/10.1016/S0140-6736(13)60900-9
• Bally, M., Dendukuri, N., Rich, B., Nadeau, L., Helin-Salmivaara, A., Garbe, E., & Brophy, J. M. (2017). Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data. BMJ, 357, j1909. https://doi.org/10.1136/bmj.j1909
• Soliman, S., Ahmed, R. M., Ahmed, M. M., Attia, A., & Soliman, A. R. (2025). Non-steroidal anti-inflammatory drugs: what is the actual risk of chronic kidney disease? A systematic review and meta-analysis. Romanian Journal of Internal Medicine, 63(1), 3-27. https://doi.org/10.2478/rjim-2024-0029
• Kaufman, D. W., Kelly, J. P., Battista, D. R., Malone, M. K., Weinstein, R. B., & Shiffman, S. (2018). Exceeding the daily dosing limit of nonsteroidal anti-inflammatory drugs among ibuprofen users. Pharmacoepidemiology and Drug Safety, 27(3), 322-331. https://doi.org/10.1002/pds.4391
• Machado, G. C., Maher, C. G., Ferreira, P. H., Day, R. O., Pinheiro, M. B., & Ferreira, M. L. (2017). Non-steroidal anti-inflammatory drugs for spinal pain: a systematic review and meta-analysis. Annals of the Rheumatic Diseases, 76(7), 1269-1278. https://doi.org/10.1136/annrheumdis-2016-210597
• Su, H., Liu, R., Chang, M., Huang, J., & Wang, X. (2017). Dietary linoleic acid intake and blood inflammatory markers: a systematic review and meta-analysis of randomized controlled trials. Food & Function, 8(9), 3091-3103. https://doi.org/10.1039/c7fo00433h
• Grytten, E., Laupsa-Borge, J., Cetin, K., Bohov, P., Nordrehaug, J. E., Skorve, J., Berge, R. K., Strand, E., Bjørndal, B., Nygård, O. K., Rostrup, E., Mellgren, G., & Dankel, S. N. (2025). Inflammatory markers after supplementation with marine n-3 or plant n-6 PUFAs: A randomized double-blind crossover study. Journal of Lipid Research, 66(4), 100770. https://doi.org/10.1016/j.jlr.2025.100770
• Flock, M. R., Skulas-Ray, A. C., Harris, W. S., Etherton, T. D., Fleming, J. A., & Kris-Etherton, P. M. (2013). Determinants of erythrocyte omega-3 fatty acid content in response to fish oil supplementation: a dose-response randomized controlled trial. Journal of the American Heart Association, 2(6), e000513. https://doi.org/10.1161/JAHA.113.000513
• McGraw, K. E., Riggs, D. W., Rai, S., Navas-Acien, A., Xie, Z., Lorkiewicz, P., Lynch, J., Zafar, N., Krishnasamy, S., Taylor, K. C., Conklin, D. J., DeFilippis, A. P., Srivastava, S., & Bhatnagar, A. (2021). Exposure to volatile organic compounds – acrolein, 1,3-butadiene, and crotonaldehyde – is associated with vascular dysfunction. Environmental Research, 196, 110903. https://doi.org/10.1016/j.envres.2021.110903
• Ramsden, C. E., Zamora, D., Faurot, K. R., MacIntosh, B., Horowitz, M., Keyes, G. S., Yuan, Z.-X., Miller, V., Lynch, C., Honvoh, G., Park, J., Levy, R., Domenichiello, A. F., Johnston, A., Majchrzak-Hong, S., Hibbeln, J. R., Barrow, D. A., Loewke, J., Davis, J. M., … Mann, J. D. (2021). Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial. BMJ, 374, n1448. https://doi.org/10.1136/bmj.n1448

Related reading

• Screening for Hyperinsulinemia in Patients With Neuropathic Pain
• Carpal Tunnel and Diabetes: Hand Diagnoses as Screening Triggers
• Arterial Stiffness and Endothelial Function

Screening for Hyperinsulinemia in Patients With Neuropathic Pain

Screen patients with neuropathic or chronic pain for hyperinsulinemia by drawing fasting insulin together with fasting glucose so HOMA-IR is available. Glucose and HbA1c stay in range while insulin output rises, so repeat the insulin on the same platform and read it against outcome-derived thresholds as well as the manufacturer interval.

Glucose-based screening finds dysglycemia late by design. In patients with neuropathic or chronic pain, hyperinsulinemia and the small-fiber and endothelial changes that travel with it are often established years before HbA1c crosses the prediabetes line.

Hyperinsulinemia is the compensatory state that glucose-based screening is structurally unable to see. Fasting glucose and HbA1c stay in range precisely because insulin output is rising, so a panel that stops at glycemia reads as normal through the years in which endothelial function, small-fiber density and pain sensitivity are already changing.

Dr. Padda’s video The Hormone Nobody Measured Is Starving Your Nerves summarizes Chapter 4 of The Pained Brain (Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD). For practices evaluating Measura [Cardiometabolic and Autonomic Health Analysis], the screening questions are specific: which patients with neuropathic or chronic pain warrant an insulin-axis workup, how to interpret an unstandardized assay, and what a positive result changes.

Can you have hyperinsulinemia without diabetes?

In Whitehall II, future diabetes cases carried 34.2% lower HOMA2 insulin sensitivity than controls at the earliest observation, 13 years before diagnosis. Beta-cell output peaked at 92.6% of reference three years out, and fasting glucose rose from 5.47 to 5.79 mmol/L before turning sharply upward late. A Japanese health-examination cohort of 27,392 adults found insulin-sensitivity separation ten years before a prediabetes diagnosis, at fasting glucose of 91.8 against 89.6 mg/dL, placing onset more than 20 years before diagnosis in most patients.

On hyperinsulinemic-euglycemic clamp testing, normoglycemic hyperinsulinemic subjects disposed of glucose at 6.23 mg/kg/min, statistically indistinguishable from impaired glucose tolerance at 6.37 and new type 2 diabetes at 6.19, against 11.88 in normal controls. The control group was only five people, but the conclusion does not rest on that number.

Why isn’t fasting insulin on the standard panel, and how should it be read?

The American Diabetes Association workgroup that compared commercial insulin methods in 2007 found among-assay variation with a median of 24% and a ceiling of 66%. Its 2010 statement concluded that no criteria existed to classify an individual as insulin resistant and proposed a sequence: standardize the assay, let research define cutoffs, then write guidelines. The first step is still unfinished. In 2025, one of twelve immunoassays matched isotope-dilution mass spectrometry, and there is still no listed reference method or certified reference material. The 2025 Standards of Care define prediabetes by glucose and HbA1c and name no fasting insulin or HOMA-IR recommendation.

That argues for disciplined interpretation, not omission. Draw fasting insulin together with fasting glucose so HOMA-IR is available, repeat on the same platform, and read the value against outcome-derived thresholds as well as the manufacturer interval. In the Tehran Lipid and Glucose Study, cut points predicting incident diabetes were 9.16 microU/mL in men and 11.13 in women. A reference interval built from screened-healthy Brazilian adults topped out at 13.14, with medians near 6.6.

Can hyperinsulinemia damage small nerve fibers before diabetes is diagnosed?

The neuropathy literature has pointed at the prediabetic window for 25 years. Of 107 patients with painful sensory neuropathy labeled idiopathic, 34% had impaired glucose tolerance on a two-hour test despite normal fasting glucose and HbA1c. In a population survey of 4,002 adults, neuropathy prevalence ran 3.25%, 6.29% and 15.12% across normoglycemia, prediabetes and diabetes. In the KORA cohort, each 5 cm of waist raised the odds of incident distal sensorimotor polyneuropathy by 22%, with no modification by diabetes status.

Detection is method-dependent. In the Heidelberg cohort, a full quantitative sensory battery identified neuropathy in 71% of prediabetic patients against 11% on the standard deficit score, conduction studies missed 58% of battery-positive cases, and hyperalgesia was present in more than half. The damage also tracks the insulin axis. Among 5,249 Danes with recently diagnosed type 2 diabetes, the adjusted prevalence ratio for questionnaire-defined polyneuropathy was 1.72 with elevated C-peptide versus 1.42 with elevated HbA1c, and in progressing diabetic neuropathy, triglycerides were the only baseline laboratory value that correlated with a 25% one-year loss of myelinated fiber density. The evidence is not unanimous; Olmsted County cohorts found no prediabetic excess of sensory symptoms or change, so this is a majority reading of the literature.

Can pain and steroid treatment raise insulin resistance?

The relationship runs both ways, which matters most in pain practices. Thirty minutes of experimental painful stimulation reduced insulin-stimulated glucose uptake in ten healthy men from 6.37 to 4.97 mg/kg/min, a 22% fall, with cortisol and epinephrine rising twofold to threefold. Total hip replacement reduced whole-body insulin sensitivity 43% in fasted patients and 18% with a preoperative carbohydrate drink. Two weeks of prednisolone lowered insulin sensitivity dose-dependently in healthy young men and cut insulin-stimulated capillary recruitment by 9% and 17%. Dr. Padda’s position is to have the insulin value in hand before a glucocorticoid injection, which is used as a bridge rather than the plan.

How do you test for hyperinsulinemia, and what does a positive result change?

Candidates include patients with painful neuropathy labeled idiopathic; chronic pain with central adiposity, elevated triglycerides or low HDL at normal glucose; fibromyalgia and migraine patients, in whom insulin resistance has been reported in some cohorts and not others; and patients facing repeated glucocorticoid exposure. Measurements matched to the mechanism:

• Laboratory panels with fasting glucose, HbA1c and lipids, with fasting insulin requested so HOMA-IR can be calculated, and C-peptide where the insulin axis is in question.
• Sudomotor testing, which assesses sweat-gland function mediated by distal small fibers, the fibers conduction studies do not sample.
• Arterial stiffness and endothelial function, because selective insulin resistance impairs the nitric oxide arm; among 40 obese nondiabetic adults, flow-mediated dilation was 9.2% in the most resistant HOMA-IR tertile against 18.0% in the least.
• Bioimpedance body composition, since central adiposity carries neuropathy risk independent of glycemic category.

A positive finding reframes part of the pain problem as metabolic and establishes a baseline. The intervention evidence favors reducing insulin demand over lowering glucose by any route: a year of supervised exercise raised distal leg intraepidermal nerve fiber density by 1.5 fibers/mm in type 2 diabetes with no HbA1c change, while the intensive glycemic arm of ACCORD showed a hazard ratio of 0.95 for the composite including neuropathy, with weight gain, severe hypoglycemia and excess mortality. That reading is inference across trials not designed to test insulin, and it should be charted as such. Pace matters too: reported nerve injuries during rapid weight loss on newer agents clustered at a median of 3.7 kg per month.

Documentation, fall risk and workflow

Put the insulin-axis panel on a standing order triggered by neuropathic symptoms or a pain diagnosis with metabolic features, so the order does not depend on who sees the patient. In older patients, a small-fiber deficit is also a fall-risk data point, so pair it with the balance and memory workup described in cognitive assessment and fall prevention. Annual wellness visits and MIPS or HEDIS cardiometabolic measures can carry the documentation, as outlined in MIPS and quality reporting.

In Dr. Padda’s practice every new patient has a fasting insulin drawn before any procedure. The share of US adults who are metabolically healthy is under 12.2% on NHANES 2009 to 2016 and under 7% on the tighter post-2021 criteria; in that clinic population it is under 3% overall and under 1% of chronic pain patients. Read the clinic numbers honestly, as practice-reported figures from our own population, not trial outcomes, and individual results vary, which is why the study-level detail sits in the book companion for Chapter 4.

Frequently asked questions

References

• Tabák, A. G., Jokela, M., Akbaraly, T. N., Brunner, E. J., Kivimäki, M., & Witte, D. R. (2009). Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet, 373(9682), 2215–2221. https://doi.org/10.1016/S0140-6736(09)60619-X
• Yang, G., Li, C., Gong, Y., Fang, F., Tian, H., Li, J., & Cheng, X. (2015). Assessment of Insulin Resistance in Subjects with Normal Glucose Tolerance, Hyperinsulinemia with Normal Blood Glucose Tolerance, Impaired Glucose Tolerance, and Newly Diagnosed Type 2 Diabetes (Prediabetes Insulin Resistance Research). Journal of Diabetes Research, 2016, 9270768. https://doi.org/10.1155/2016/9270768
• Marcovina, S., Bowsher, R. R., Miller, W. G., Staten, M., Myers, G., Caudill, S. P., Campbell, S. E., & Steffes, M. W., for the Insulin Standardization Workgroup (2007). Standardization of insulin immunoassays: report of the American Diabetes Association Workgroup. Clinical Chemistry, 53(4), 711–716. https://doi.org/10.1373/clinchem.2006.082214
• Rohlfing, C., Petroski, G., Hatten-Beck, M., Hanson, S., Hoofnagle, A. N., Little, R. R., & Kabytaev, K. (2025). The current status of serum insulin measurements and the need for standardization. Clinical Chemistry and Laboratory Medicine, 63(12), 2442–2446. https://doi.org/10.1515/cclm-2025-0552
• Ghasemi, A., Tohidi, M., Derakhshan, A., Hasheminia, M., Azizi, F., & Hadaegh, F. (2015). Cut-off points of homeostasis model assessment of insulin resistance, beta-cell function, and fasting serum insulin to identify future type 2 diabetes: Tehran Lipid and Glucose Study. Acta Diabetologica, 52(5), 905–915. https://doi.org/10.1007/s00592-015-0730-3
• Singleton, J. R., Smith, A. G., & Bromberg, M. B. (2001). Increased prevalence of impaired glucose tolerance in patients with painful sensory neuropathy. Diabetes Care, 24(8), 1448–1453. https://doi.org/10.2337/diacare.24.8.1448
• Kopf, S., Groener, J. B., Kender, Z., Fleming, T., Bischoff, S., Jende, J., Schumann, C., Ries, S., Bendszus, M., Schuh-Hofer, S., Treede, R.-D., & Nawroth, P. P. (2018). Deep phenotyping neuropathy: An underestimated complication in patients with pre-diabetes and type 2 diabetes associated with albuminuria. Diabetes Research and Clinical Practice, 146, 191–201. https://doi.org/10.1016/j.diabres.2018.10.020
• Christensen, D. H., Knudsen, S. T., Gylfadottir, S. S., Christensen, L. B., Nielsen, J. S., Beck-Nielsen, H., Sørensen, H. T., Andersen, H., Callaghan, B. C., Feldman, E. L., Finnerup, N. B., Jensen, T. S., & Thomsen, R. W. (2020). Metabolic Factors, Lifestyle Habits, and Possible Polyneuropathy in Early Type 2 Diabetes: A Nationwide Study of 5,249 Patients in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) Cohort. Diabetes Care, 43(6), 1266–1275. https://doi.org/10.2337/dc19-2277
• Greisen, J., Juhl, C. B., Grøfte, T., Vilstrup, H., Jensen, T. S., & Schmitz, O. (2001). Acute pain induces insulin resistance in humans. Anesthesiology, 95(3), 578–584. https://doi.org/10.1097/00000542-200109000-00007
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Imaging for Low Back Pain and the Metabolic Workup the MRI Skips

Early imaging does not help uncomplicated low back pain: six randomized trials pooling 1,804 patients found no gain in pain or function, and the ACR reserves imaging for suspected cauda equina syndrome, cancer, fracture or infection, or for failure of six weeks of treatment.

Guideline-concordant imaging for low back pain is well defined and poorly followed. The larger gap is what goes unordered: the metabolic and vascular data that separate a symptomatic finding from an incidental one.

Imaging for low back pain has one of the clearest evidence bases in primary care and one of the weakest adherence records. The less discussed problem is substitution: the MRI answers a structural question the patient rarely needed answered, while the metabolic and vascular data that distinguish a symptomatic finding from an incidental one go unmeasured.

The argument is laid out in Dr. Padda’s video Your MRI Is Lying to You, drawn from Chapter 3 of The Pained Brain (Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD). For a practice considering Measura [Cardiometabolic and Autonomic Health Analysis], the relevant questions are narrower: which back and joint pain patients warrant a terrain workup, what a positive finding changes, and how to make the order reproducible.

What are the guidelines for imaging for low back pain?

Six randomized trials pooling 1,804 patients without indications of serious disease found that immediate imaging did not improve pain or function; the long-term pain effect was -0.04. The ACR Appropriateness Criteria describe uncomplicated acute low back pain as not warranting imaging, reserving it for suspected cauda equina syndrome, malignancy, fracture or infection, or for failure of up to six weeks of medical management and physical therapy.

Practice diverges in both directions. Across 45 studies, 24.8% of primary care and 35.6% of emergency department back pain visits ended in imaging, and the CT and MRI share rose 53.5% between 1995 and 2015. Roughly a third of lumbar referrals lacked a red flag, while 65.6% of patients who had one were never imaged. The flags themselves perform poorly: among 1,172 consecutive primary care patients, 0.9% had serious pathology and 80.4% carried at least one flag. The Cochrane review of flags for vertebral fracture found most not useful, with age over 70 the exception at a positive likelihood ratio of 11.19.

Does an early MRI for back pain lead to more procedures?

Nonadherent imaging shows up as downstream procedures. In 3,022 workers’ compensation claims, less severely injured workers with an early MRI had a relative risk of 27.40 for injections and 28.35 for surgery against the no-MRI referent, and comparing early with timely MRI inside the same severity band still left a surgical relative risk of 4.38. Among 405,965 matched veteran episodes without red flags, a setting where fee-for-service incentive is largely absent, lumbar surgery within a year ran 1.48% after an inappropriate early MRI against 0.12%, and prescription opioids 35.1% against 28.6%. The last recorded pain score was marginally higher in the scanned group, 3.99 against 3.87.

Report language compounds the effect. A stepped-wedge trial that inserted age-specific prevalence benchmarks into 238,886 spine imaging reports moved twelve-month spine-related utilization by -0.7%, a null result. In a small randomized trial, patients given a descriptive finding-by-finding account of their MRI catastrophized more and functioned worse at six weeks than patients given a clinical explanation. A printed sentence of context does not neutralize the image; the explanation delivered by the clinician is the lever with trial evidence behind it.

Why do some spine MRI findings hurt and others do not?

The most direct case for a terrain workup comes from the Wakayama Spine Study. Among 451 community residents with moderate radiographic canal stenosis on whole-spine MRI, symptomatic and asymptomatic residents did not differ by age, sex, smoking or body mass index (23.7 against 23.1). Diabetes separated them at an odds ratio of 3.92, present in 25.0% of the symptomatic group against 6.4%, and a low ankle-brachial index separated them at 1.36 per standard deviation. In severe stenosis nothing separated the groups. The symptomatic cell is small and the design is cross-sectional, but the selection implication is clear: at intermediate structural severity, the discriminating data sit in the blood and the arteries.

The degenerative findings track the same terrain. Pooled Mendelian randomization estimates put genetically predicted body mass index and waist circumference at 1.26 each for disc degeneration, triglycerides at 1.08 and type 2 diabetes at 1.05. Observationally, diabetes carried 1.68 times the odds across 2,881,170 adults, settling at 1.47 once code-based database studies were removed. In Framingham, aortic calcification anterior to a vertebral level predicted disc deterioration at that level over 25 years at an odds ratio of 1.5, consistent with a disc that depends on diffusion from segmental vessels. Outside the spine, metabolic syndrome carried a relative risk of 1.72 for enlarging medial bone marrow lesions in the knee, and diabetes carried odds of 3.69 for frozen shoulder and 2.24 for rotator cuff tendinopathy.

Which back pain patients need a metabolic workup, and which tests?

A workable selection frame for pain, primary care and geriatrics panels: back or joint pain where imaging severity and symptoms are discordant; moderate stenosis with neurogenic or vascular claudication in the differential; pain patients with central adiposity, known dysglycemia or dyslipidemia; and any patient whose workup has been imaging-heavy and laboratory-light. The criteria are summarized in selection criteria.

• Laboratory panels: HbA1c, fasting glucose, triglycerides and HDL cholesterol, the variables with the most direct support above.
• Ankle-brachial index: the vascular variable that separated symptomatic from asymptomatic moderate stenosis in Wakayama.
• Bioimpedance body composition: in 223 knee replacement candidates, bioimpedance fat mass correlated with lower pressure pain thresholds at every site, including the forehead, while body mass index correlated with none.
• Arterial stiffness and endothelial function: a functional read on the vascular bed that avascular tissue depends on.

What a finding changes in management

A metabolic or vascular finding does not replace imaging when a red flag is present, and Measura performs no imaging. It changes three things. Sequencing: history, examination and laboratory data come first, the image is read last and against all three, and a needle placed for a reason the examination supplied is framed as a bridge that buys time for terrain repair rather than as the plan. Explanation: the patient hears that the report describes shape while the measured values describe risk that can be tracked. Follow-up: a repeatable baseline turns a lifestyle recommendation into a monitored intervention.

Sleep belongs in the same conversation, because it is a behavioral input with a measurable effect on the pain threshold. Two nights of fragmented sleep lowered heat pain thresholds in healthy adults, with 34.9% of the effect mediated by monocyte inflammatory output. Work schedules and caregiving load drive that input as much as any clinical variable does, and none of it appears on a spine report.

Documentation and workflow

The workup is reproducible only when it is protocolized rather than remembered. A standing order keyed to a discordant-imaging or symptomatic-stenosis trigger removes the dependence on individual recall. The same data serve the annual wellness visit, where cardiovascular risk factors are already documented, and quality programs such as MIPS and HEDIS where cardiometabolic measures apply. For older patients, in whom age over 70 is the flag that carries weight for vertebral fracture, file results where the fall-prevention and memory workup already lives, as described in cognitive assessment and fall prevention. Reports return to the ordering physician, and interpreting the report covers how to read them. The evidence behind each figure is in the book companion for Chapter 3.

Frequently asked questions

References

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• Meert, L., Vervullens, S., Heusdens, C. H. W., Smeets, R. J. E. M., Meeus, M., & Mertens, M. G. C. A. M. (2024). Unravelling relationships between obesity, diabetes, and factors related to somatosensory functioning in knee osteoarthritis patients. Clinical Rheumatology, 43(8), 2637–2645. https://doi.org/10.1007/s10067-024-07022-2

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