The Volume Knob Is Not in the Knee | The Pained Brain, Chapter 9

Fibromyalgia · Small fiber neuropathy

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

Should every fibromyalgia patient have small-fiber testing?

Not reflexively. A pooled prevalence near 49 percent is high, but the pathology does not explain the sensory phenotype, so its value lies in the treatable-cause search and a documented baseline. Noninvasive sudomotor measurement fits a primary care workflow, with skin biopsy reserved for cases where the tissue answer would change the workup. See specialty applications of autonomic and sudomotor testing.

Does a normal CRP argue against central sensitization?

No. In surgical spine patients, inflammatory proteins were elevated in cerebrospinal fluid while serum proteins ran below controls, and in the knee-pain cohort CRP was unrelated to low thresholds while visceral fat and leptin were related. Serum inflammation and central amplification can diverge, so a normal CRP closes very little. Review how terrain findings are reported.

Is the Central Sensitization Inventory adequate for screening?

As a screen for the syndrome it is useful; as a measure of nociceptive gain it is not. It tracks psychological constructs strongly, although a separate meta-analysis of 33 studies found significant correlation with pressure threshold, about half of those effects medium to large. A high score is a reason to measure objectively, not a diagnosis. Read how standing orders make screening reproducible.

How does autonomic measurement relate to central sensitization?

Heart-rate variability was one component of the cardiometabolic load that predicted spinal facilitation in adults with no pain, and pooled data place autonomic small-fiber impairment at 45 percent in fibromyalgia. Autonomic testing describes the terrain rather than the amplifier, and it earns its place as a trendable baseline in the record. See autonomic nervous system testing.

Where do Measura results go?

Findings are reported to the ordering physician. Measura does not diagnose disease on its own or treat, and it does not make medication decisions. Structured results can be filed into the chart beside the pain history and the cognitive baseline. Learn how results reach the record.

Can you have fibromyalgia and small fiber neuropathy at the same time?

Yes, and often. 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 that figure. Pooled data also place autonomic small-fiber impairment at 45 percent. The overlap is real, which is why a noninvasive sudomotor read belongs in the workup of widespread pain.

Does small fiber neuropathy cause fibromyalgia pain?

Not on the evidence here. When 57 consecutive fibromyalgia patients were split by biopsy result, clinical measures, sensory testing and evoked potentials did not differ between the groups. The fiber loss behaves like residue of a chronically inflamed terrain, while the pain itself is generated upstream by central amplification. The finding still matters, because the workup can uncover a treatable cause.

How is small fiber neuropathy diagnosed in fibromyalgia?

Skin biopsy remains the tissue diagnosis. Sudomotor testing gives a noninvasive read on small-fiber sudomotor function and fits a primary care workflow, but it does not replace biopsy. Heart rate variability and cardiac autonomic reflex tests describe autonomic tone. In one biopsy-positive fibromyalgia series, the workup found dysimmune markers in 8 patients and hepatitis C serology in 2.

Add Terrain Measurement to the Sensitized Patient Workup

See how the Measura protocol fits a practice that manages fibromyalgia and widespread pain, from selection criteria and standing orders to reporting into the chart.

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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