Lysophosphatidylcholine induces neuropathic pain through an action of autotaxin to generate lysophosphatidic acid

Academic Article
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publication date

  • March 2008

abstract

  • Lysophosphatidic acid receptor (LPA(1)) signaling initiates neuropathic pain and several pathological events in a partial sciatic nerve injury model. Recently, we reported that lysophosphatidic acid (LPA) induces neuropathic pain as well as demyelination and pain-related protein expression changes via LPA(1) receptor signaling. Lysophosphatidylcholine (LPC), also known as lysolecithin, which is hydrolyzed by autotaxin/ATX into LPA, induces similar plastic changes. Here, we attempted to clarify whether ATX and LPA(1) receptor signaling is involved in the LPC-induced neuropathic pain. In wild-type mice, a single intrathecal (i.t.) injection of LPC induced mechanical allodynia and thermal hyperalgesia 2 days after injection; this persisted for 7 days at least. On the other hand, LPC-induced mechanical allodynia and thermal hyperalgesia were completely abolished in mice lacking an LPA(1) receptor gene. Furthermore, the LPC-induced response was also significantly, but partially reduced in heterozygous mutant mice for the ATX gene. These findings suggest that intrathecally-injected LPC is converted to LPA by ATX, and this LPA activates the LPA(1) receptor to initiate neuropathic pain.