Chronic pain as a manifestation of potassium channel-complex autoimmunity.
OBJECTIVE
Autoantibodies targeting voltage-gated potassium channel (VGKC) complexes cause a spectrum of neuronal hyperexcitability disorders. We investigated pain as a manifestation of VGKC-complex autoimmunity.


METHODS
We reviewed the prevalence and characteristics of pain in VGKC-complex-immunoglobulin G (IgG)-seropositive patients in 25 months of comprehensive service testing for neural autoantibodies, subtyped positive sera for LGI1-IgG and CASPR2-IgG specificities, and reviewed pain prevalence in autoimmune control patients.


RESULTS
VGKC-complex-IgG was identified in 1,992 patients of 54,853 tested (4%). Of 316 evaluated neurologically at Mayo Clinic, 159 (50%) had pain, in isolation (28%) or with accompanying neurologic manifestations (72%), and not attributable to alternative cause. Pain was subacute in onset, chronic in course, neuropathic, nociceptive, regional, or diffuse and sometimes attributed to fibromyalgia (6%) or psychogenic cause (13%). Most patients had normal peripheral nervous system function, measured by neuropathy impairment scores and nerve conduction. Evidence of neuronal hyperexcitability (hyperhidrosis, quantitative heat-pain hyperalgesia, or electromyographic excitability) was 25-fold more common in pain patients. Pain management required multiple medications in 70% (narcotics, 30%); 13 of 16 patients reported pain relief with immunotherapy. Pain was significantly associated with CASPR2-IgG-positivity (16% positive with pain, 7% without pain; p = 0.014) but not with LGI1-IgG. Less than 10% of 167 patients with neural autoantibodies other than VGKC-complex-IgG reported pain.


CONCLUSIONS
Chronic idiopathic pain is a syndromic manifestation of VGKC-complex autoimmunity. Hyperexcitability of nociceptive pathways is implicated. CASPR2-IgG significantly associates with pain, but in most patients the antigenic VGKC-complex molecule remains to be determined. VGKC-complex autoimmunity represents an important new direction for pain research and therapy.
Department of Neurology, Mayo Clinic, Rochester, MN, USA. klein.christopher@mayo.edu
Christopher J
CJ
Klein
Vanda A
VA
Lennon
Paula A
PA
Aston
Andrew
A
McKeon
Sean J
SJ
Pittock
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000150:complications* / Q000453:epidemiology / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D059350:Chronic Pain / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology*; D015995:Prevalence
D001323:Autoantibodies; D007074:Immunoglobulin G; D024642:Potassium Channels, Voltage-Gated