A Woman With Multiple Neuropathic Symptoms, Hypersensitivity to Heat, Peppers, and Alcohol, With a Variant in the TRPV1 Capsaicin Receptor Gene: Possible Implications to ME/CFS

Transient receptor potential vanilloid 1 (TRPV1) is a ligand and heat‐gated ion channel expressed on nociceptors that plays a central role in thermal and chemical pain signaling. Loss‐of‐function variants in TRPV1 have been associated with reduced nociception. We report a 65‐year‐old woman with disabling polyneurofunctional/neuropathic symptomatology including migraine, functional gastrointestinal disorders, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Diagnostic evaluation revealed sensory polyneuropathy and autonomic instability. Whole genome sequencing reanalysis identified a heterozygous TRPV1 c.2174A > T (p.Lys725Met) Likely Pathogenic variant that is very rare and highly conserved. Our patient reports consistent, longstanding, marked hypersensitivity to heat, capsaicin, and alcohol, all of which are known TRPV1 agonists, supporting a gain‐of‐function mechanism for this variant. Furthermore, prior studies have implicated TRPV1 hyperactivity in migraine, nociceptive sensitization, and ME/CFS. Despite the excellent clinical correlation, causality of the variant cannot be definitively established without functional studies. This case expands the potential phenotypic spectrum associated with TRPV1, and highlights a possible role for TRPV1‐mediated channelopathies in complex neurofunctional disorders including ME/CFS.