Autoimmune regulation of chronic pain

Abstract

Chronic pain is an unpleasant and debilitating condition that is often poorly managed by existing therapeutics. Reciprocal interactions between the nervous system and the immune system have been recognized as playing an essential role in the initiation and maintenance of pain. In this review, we discuss how neuroimmune signaling can contribute to peripheral and central sensitization and promote chronic pain through various autoimmune mechanisms. These pathogenic autoimmune mechanisms involve the production and release of autoreactive antibodies fromB cells. Autoantibodies - ie, antibodies that recognize self-antigens - have been identified as potential molecules that canmodulate the function of nociceptive neurons and thereby induce persistent pain. Autoantibodies can influence neuronal excitability by activating the complement pathway; by directly signaling at sensory neurons expressing Fc gamma receptors, the receptors for the Fc fragment of immunoglobulin G immune complexes; or by binding and disrupting ion channels expressed by nociceptors. Using examples primarily fromrheumatoid arthritis, complex regional pain syndrome, and channelopathies frompotassiumchannel complex autoimmunity, we suggest that autoantibody signaling at the central nervous systemhas therapeutic implications for designing novel disease-modifying treatments for chronic pain.