Science News: Autonomic Small-Fiber Pathology in Patients With Fibromyalgia

Submitted by: Rebecca O'Bryan, MD
Edited by: Milvia Pleitez, MD

Citation: Falco P, Galosi E, Giulia Di Stefano, et al. Autonomic small-fiber pathology in patients with fibromyalgia. The journal of pain/Journal of pain. 2024;25(1):64-72. doi:https://doi.org/10.1016/j.jpain.2023.07.020

Summary: The aim of this study was to investigate whether small fiber pathology (termed SFP) associated with fibromyalgia shows evidence of damage to dermal autonomic nerve fibers, and how the damage is associated with autonomic symptoms. A total of 138 patients participated (58 patients with fibromyalgia syndrome (23 diagnosed with SFP), 48 healthy subjects, and 32 patients with diabetic or transthyretin familial amyloid small fiber neuropathy (SFN). Skin biopsy was performed to investigate intraepidermal nerve fiber density, piloerector muscle and sweat gland nerve fiber density (SGNFD). These findings were correlated with autonomic symptoms using the Composite Autonomic Symptom Score 31 question questionnaire. NCSs were performed to ensure no large fiber neuropathy was present. Diagnosis of pure SFN relied on normal NCS parameters and fulfilled the Besta criteria. These criteria are based on having at least two abnormal findings among the three commonly used to assess small-fiber damage. The criteria include, the presence of two negative clinical signs (pinprick and thermal sensory loss), possibly associated with positive clinical signs (allodynia and/or hyperalgesia), abnormal warm and/or cold thresholds at the foot as assessed with quantitative sensory testing, and reduced intraepidermal nerve fiber density (IENFD) at the distal leg. Results were notable for findings that the piloerector muscle and SGNFD were lower in patients with fibromyalgia associated SFP than that in healthy subjects. However, autonomic small-fiber damage had no correlation with autonomic symptoms severity. In patients with SFP, the intraepidermal, piloerector muscle, and SGNFD were higher than that in patients with small-fiber neuropathy.

Comments: This is an interesting study looking at small fiber neuropathy in patients with fibromyalgia. However, the method of selecting patients with SFP utilizing IENFD, then utilizing that specific group to investigate differences with healthy controls would seem to potentially bias findings specifically looking for evidence of autonomic nerve fiber damage. At best, this study shows a correlation between the presence of IENFD and that of muscle and SGNFD. This is a novel finding and does further indicate that a subset of patients with fibromyalgia have pathology associated with autonomic nerve fibers. The significance of this remains to be seen given the lack of correlation with symptoms. Understanding the underlying pathology as it relates to the peripheral nervous system is relevant. This study is a very small sample size, even smaller when those without SFP are selected out, and more research is needed.