抄録
Here I report the initiation mechanisms underlying neuropathic pain (NP) following nerve damages. In this experiment, we used partial sciatic nerve ligation (PSNL) to induce NP in mice. The abnormal chronic pain including hyperalgesia and tactile allodynia was observed 3 days after the PSNL and lasted for more than 2 weeks. We found many nociceptive fiber-specific changes in protein and/or gene expression of molecules involved in pain transmission. They include the novel expression of Ca channel alpha2-delta1 subunit in myelinated fiber DRG neurons, which may account for hyperalgesia. At the same time, we found the loss of function in unmyelinated fiber-mediated pain transmission. They include the down-regulation of substance P in dorsal horn of spinal cord. In addition to these phenotypic changes in the expression, we observed marked demyelination and remyelination in dorsal root, a phenomenon which is closely related to allodynia. All these changes were abolished in lysophosphatidic acid (LPA) receptor (LPA1) knock-out mice, and mimicked by the intrathecal single injection of LPA. In ex vivo culture system of dorsal root, the addition of LPA caused demyelination and sprouting/remyelination, which were accompanied with down-regulation of myelin basic protein expression. We also found that LPA causes microglia activation in the spinal cord. I will discuss how LPA plays the initiation role in many molecular events observed in PSNL-induced NP. [J Physiol Sci. 2006;56 Suppl:S50]
