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

Neuroscience. 2008 Mar 18;152(2):296-8. doi: 10.1016/j.neuroscience.2007.12.041. Epub 2008 Jan 9.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Hyperalgesia / chemically induced*
  • Hyperalgesia / genetics
  • Hyperalgesia / metabolism
  • Lysophosphatidylcholines*
  • Lysophospholipids / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • Pain Measurement / methods
  • Phosphodiesterase I / genetics
  • Phosphodiesterase I / metabolism*
  • Phosphoric Diester Hydrolases
  • Pyrophosphatases / genetics
  • Pyrophosphatases / metabolism*
  • Reaction Time / drug effects
  • Receptors, Lysophosphatidic Acid / deficiency
  • Time Factors


  • Lysophosphatidylcholines
  • Lysophospholipids
  • Multienzyme Complexes
  • Receptors, Lysophosphatidic Acid
  • Phosphoric Diester Hydrolases
  • Phosphodiesterase I
  • alkylglycerophosphoethanolamine phosphodiesterase
  • Pyrophosphatases
  • lysophosphatidic acid