Role of Central Sensitization Syndrome in Patients With Autonomic Symptoms

Idiosyncratic autonomic-like symptomatology, e.g., when objective autonomic tests cannot fully explain autonomic concerns, is poorly understood. We hypothesize that central sensitization plays a role in the autonomic symptoms-sings dichotomy.

This retrospective case-control study was conducted at Brigham and Women's Faulkner Hospital Autonomic Laboratory between 2022 and 2023 and analyzed patients who completed autonomic testing that included surveys (Central Sensitization Inventory [assessing central sensitization syndrome {CSS}], Compass-31 [assessing autonomic symptoms], Neuropathy Total Symptom Score-6 [assessing sensory symptoms]) and autonomic (Valsalva maneuver, deep breathing, sudomotor evaluation, and head-up tilt), cerebrovascular (cerebral blood flow velocity [CBFv]), respiratory (capnography), and neuropathic (skin biopsies for assessment of small fiber neuropathy) testing.

In total, 555 patients were enrolled and 455 (78%) satisfied criteria for CSS. Patients with CSS were younger and more frequently female and had longer duration of symptoms, more comorbidities, and higher Compass-31 scores and NTSS-6 compared with non-CSS patients. Autonomic testing showed lower orthostatic end-tidal CO₂ (p = 0.002) and larger orthostatic decline in CBFv (p < 0.001) in the CSS group. There was no difference in the peripheral nervous system markers (sudomotor tests and skin biopsies). The frequency of moderate autonomic failure (AF) (91.4% vs 95%, p = 0.321) was similar between the groups, but the CSS group had lower AF score (4.21 ± 3.34 vs 5.23 ± 4.08, p < 0.021).

CSS is present in most patients with chronic autonomic concerns. Central sensitization amplifies autonomic symptoms presumably through perturbed interoceptive processing and can be an underlying mechanism driving idiosyncratic autonomic-like symptomatology. Patients with CSS had objective evidence of autonomic impairment; however, it was less severe than in non-CSS patients. Our study shows that CSS and AF coexist and both conditions need to be treated.