Autonomic dysfunction in fibromyalgia syndrome: the role of small fiber damage

Objective: Cardiovascular autonomic symptoms, particularly orthostatic intolerance, are frequent in fibromyalgia syndrome (FMS) and markedly contribute to disability, yet their underlying mechanisms remain unclear. Small fiber pathology (SFP), detected in 30–50% of patients with FMS, may also involve postganglionic sympathetic fibers. This study examined the contribution of SFP to autonomic dysfunction and cardiovascular autonomic symptoms in FMS. Methods: We prospectively enrolled 43 patients with FMS reporting orthostatic intolerance and 20 age- and sex-matched healthy controls. All participants underwent comprehensive cardiovascular autonomic testing, including head-up tilt, Valsalva maneuver, deep breathing, and spectral analysis of heart rate variability (HRV). Skin biopsies quantified intraepidermal (IENFD) and autonomic small-fiber densities, and patients were stratified into FMS with or without SFP. Results: Compared with healthy controls, patients with FMS showed reduced HRV, diminished parasympathetic modulation, and increased sympathetic predominance, together with impaired dynamic sympathetic recruitment during tilt. Although these abnormalities were present across the FMS cohort, patients with SFP displayed greater impairment across autonomic parameters, with more pronounced tachycardic responses and more severe orthostatic symptoms during tilt. Small fiber damage also correlated with indices of sympathetic hyperactivity, while no associations were observed between autonomic parameters and pain severity. Conclusions: Cardiovascular autonomic dysfunction in FMS reflects alterations in central autonomic networks, partially modulated by peripheral small fiber damage. Significance: Identifying SFP as a contributor to autonomic disturbances in FMS may aid patient stratification and support targeted therapeutic strategies.