Figure 1.

Autoimmune nature of pain from mechanical stimulation in females (a hypothesis diagram).

The myelin sheath of large mechanosensory Aβ-afferents contains auto-antigens, such as myelin basic protein (MBP). After peripheral nervous system (PNS) injury, matrix metalloproteinases (MMPs) and other proteases release the pro-nociceptive, cryptic T cell epitopes on myelin, normally sheltered from immunosurveillance. Schwann cells present MBP epitopes on the surface via major histocompatibility complex (MHC) class II (MHC II), promoting selective T cell homing to A-afferents (but not C-afferents) via T cell receptor (TCR). The repeated release and exposure of MBP epitopes and formation of MBP-specific T cell clones sustain the state of mechanical allodynia. In the spinal cord, activated microglia and adaptive, presumably, T cell signaling, are differentially active in females.