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

作者：Ueda Hiroshi^*; Ueda Mutsumi

来源：Clinical Lipidology, 2011, 6(2): 147-158.

DOI：10.2217/CLP.10.88

• allodynia
• autotaxin
• calpain
• Ca-v alpha 2 delta I
• dennyelination
• hypoesthesia
• lysophosphatidic acid
• microglia
• neuropathic pain

The injury-induced intense stimulation of spinal cord neurons causes lysophosphatidic acid (LPA) synthesis. LPA(1) 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 LPA(1) receptor signal also initiates the upregulation of Ca-v alpha 2 delta I in dorsal root ganglia and PKC-gamma 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 LPA(3) receptor mediates microglia activation at the early stage after nerve injury and LPA-induced LPA biosynthesis. Thus, both LPA(1) and LPA(3) receptors play key roles in the initiation step for neuropathic pain.

• 出版日期2011-4