Role of myelin auto-antigens in pain: a female connection.

Abstract

Following injury to the peripheral nerve, pain secondary to low threshold innocuous mechanical stimulation (mechanical allodynia) is commonly observed. Its origins are poorly understood and the pain is often refractory to common analgesic therapeutics. The past two decades has brought major advances in our understanding of the complexity of systems that underlie processing of neuropathic pain (pain arising from damage or disease of the somatosensory system). Beginning with the argument by Robert Galambos in the 1960s that glia played a major regulatory role in neural function, current thinking has evolved to emphasize the major role of glia-mediated neuroinflammation in the development of a chronic pain state. Recent use of unbiased high-throughput genetic and proteomics screening technology in preclinical models of nerve injury associated with pain states, attention has become focused on the role of T cell related genes and adaptive immune pathways (Costigan et al., 2009; Liu et al., 2012). In this perspective, we discuss the organizing principle that following local nerve injury, the ability to evoke a pain state with low-threshold, otherwise innocuous, mechanical stimulation (light touch), represents a local, sex dependent, manifestation of an adaptive immune response mediated by myelin basic protein (MBP).