Lysophosphatidylcholine induces neuropathic pain through an action of autotaxin to generate lysophosphatidic acid.
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.
Inoue
M
M
Division of Molecular Pharmacology and Neuroscience, Nagasaki University, Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki, 852-8521, Japan.
Xie
W
W
Matsushita
Y
Y
Chun
J
J
Aoki
J
J
Ueda
H
H
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D043264:Phosphodiesterase I / Q000235:genetics / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism*; D011930:Reaction Time / Q000187:drug effects; D049368:Receptors, Lysophosphatidic Acid / Q000172:deficiency; D013997:Time Factors; D000099189:Lysophospholipase D
D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D009097:Multienzyme Complexes; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D049368:Receptors, Lysophosphatidic Acid; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid