Evidence for spinal disinhibition as a pain-generating mechanism in fibromyalgia syndrome 2025 Marshall et al

Evidence for spinal disinhibition as a pain-generating mechanism in fibromyalgia syndrome

Marshall, Annea,b; Burgess, Jamiea,b; Goebel, Andreasa,c; Frank, Bernharda,c; Alam, Uazmana,b,d,e; Marshall, Andrewa,f

Introduction:

Pain phenomenology in patients with fibromyalgia syndrome (FMS) shows considerable overlap with neuropathic pain. Altered neural processing leading to symptoms of neuropathic pain can occur at the level of the spinal cord, and 1 potential mechanism is spinal disinhibition. A biomarker of spinal disinhibition is impaired H-reflex rate-dependent depression (HRDD).

Objectives:

This study investigated whether patients with FMS exhibit evidence of spinal disinhibition.

Methods:

Thirty-one individuals with FMS and 20 healthy volunteers underwent testing of Hoffman reflex including HRDD, along with assessment of clinical signs and symptoms, pressure pain thresholds, temporal summation of pain (wind-up), and conditioned pain modulation (CPM). Small nerve fibre structure was quantified using intraepidermal nerve fibre density and corneal confocal microscopy.

Results:

Patients with FMS had significantly impaired HRDD at 1 Hz (P = 0.026) and 3 Hz (P = 0.011) and greater wind-up ratio (P = 0.008) compared with healthy controls. Patients with the most impaired HRDD also had the most inefficient CPM but HRDD was not associated with wind-up. Both HRDD and CPM were most impaired in patients with a shorter duration of disease.

Conclusion:

We demonstrate for the first time that people with FMS show evidence of spinal disinhibition, which is most dominant in shorter duration of disease and may represent a putative mechanism of pain generation in FMS. Identifying people with impairment of central pain processing at an early stage may provide opportunities for targeted mechanistically directed interventions. Longitudinal studies are warranted to tease out the precise contribution of these mechanisms.

Full text available:

https://journals.lww.com/painrpts/fulltext/2025/02000/evidence_for_spinal_disinhibition_as_a.16.aspx

 

Note that Hoffman reflex is a muscular reflex (due to muscle spindle afferents). It is not a pain signal and some people are naturally hyper-reflexive.

The effect size for the H-reflex rate-dependent depression wasn't super large and there was substantial overlap between patients and controls.

Note that the CPM and wind-up testing is still subjective - participants rate pain during the test and so there can be biases (increased reporting of pain in patients) in rating that are independent of actual nociception.

 

So supposedly a negative result for small fiber neuropathy. This would be contradicting their own meta-analysis
A systematic review and meta-analysis of the prevalence of small fiber pathology in fibromyalgia: Implications for a new paradigm in fibromyalgia etiopathogenesis.