Loss of spinal substance P pain transmission under the condition of LPA1 receptor-mediated neuropathic pain.
Among various machineries occurring in the experimental neuropathic pain model, there exists the loss of pain transmission through C-fiber neurons as well as the hypersensitivity through A-fibers. The current study reveals that molecular machineries underlying the latter hypersensitivity are derived from the events through LPA1 receptor and its downstream RhoA-activation following peripheral nerve injury. The loss of C-fiber responses, which are mediated by spinal substance P (SP) pain transmission was observed with the nociceptive flexor responses by intraplantar injection of SP in nerve-injured mice. The immunohistochemistry revealed that SP signal in the dorsal horn was markedly reduced in such mice. All these changes were completely abolished in LPA1-/- mice or by the pretreatment with BoNT/C3, a RhoA inhibitor. In addition, the loss of C-fiber responses and the down-regulation of spinal SP signal induced by single intrathecal LPA injection were also abolished in such treatments. All these results suggest that the loss of pain transmission through polymodal C-fiber neurons is also mediated by the LPA1 activation following nerve injury.
Inoue
Makoto
M
Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. minoue@net.nagasaki-u.ac.jp
Yamaguchi
Asuka
A
Kawakami
Megumi
M
Chun
Jerold
J
Ueda
Hiroshi
H
D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D007150:Immunohistochemistry; D007278:Injections, Spinal; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009437:Neuralgia / Q000209:etiology / Q000503:physiopathology*; D017933:Peripheral Nervous System / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000502:physiology*; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D013116:Spinal Cord / Q000378:metabolism; D013373:Substance P / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism
D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D013373:Substance P; D001905:Botulinum Toxins; D020742:rhoA GTP-Binding Protein