Lysophosphatidic acid as the initiator of neuropathic pain

Abstract

The injury-induced intense stimulation of spinal cord neurons causes lysophosphatidic acid (LPA) biosynthesis. LPA1 receptor activation causes demyelination and sprouting of dorsal root fibers, leading to an induction of synaptic reorganization underlying allodynia, in which innocuous (tactile) stimuli cause intense pain. The LPA1 signal also initiates the up-regulation of Cavα2δ1 in dorsal root ganglion and PKCγ in the dorsal horn, underlying mechanisms for characteristic neuropathic hyperalgesia in myelinated sensory (A-type) fibers. On the other hand, the LPA3 receptor mediates microglia activation at the early stage after nerve injury and LPA-induced LPA biosynthesis. Thus, both the LPA1 and LPA3 receptors play key roles in the initiation step using a feed-forward system for neuropathic pain. © 2011 Pharmaceutical Society of Japan.