Lysophosphatidic acid as an initiator of neuropathic pain: biosynthesis and demyelination

Abstract

The injury-induced intense stimulation of spinal cord neurons causes lysophosphatidic acid (LPA) synthesis. LPA1 receptor activation causes demyelination and sprouting of sensory fibers,leading to an induction of synaptic reorganization underlying allodynia, a phenomenon that causes intense pain by innocuous stimuli such as touch. the LPA1 receptor signal also initiates the upregulation of Cava2d1 in dorsal root ganglia and PKC.g . in the dorsal horn and the downregulation of substance P in the dorsal horn, which are underlying mechanisms for characteristic neuropathic hyperalgesia in myelinated sensory (A-type) fibers and unmyelinated sensory (C-type) fiber hypoesthesia(a type of sensory loss), respectively. On the other hand, the LPA3 receptor mediates microglia activation at the early stage after nerve injury and LPA-induced LPAbiosynthesis. Thus, both LPA1 and LPA3 receptors play key roles in the initiation step for neuropathic pain.