Loss of spinal substance P pain transmission under the condition of LPA1 receptor-mediated neuropathic pain

Mol Pain. 2006 Aug 16;2:25. doi: 10.1186/1744-8069-2-25.

Abstract

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.

Publication types

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

MeSH terms

  • Animals
  • Botulinum Toxins / pharmacology
  • Immunohistochemistry
  • Injections, Spinal
  • Lysophospholipids / metabolism
  • Lysophospholipids / pharmacology
  • Lysophospholipids / physiology
  • Male
  • Mice
  • Mice, Knockout
  • Nerve Fibers, Unmyelinated / drug effects
  • Nerve Fibers, Unmyelinated / metabolism
  • Nerve Fibers, Unmyelinated / physiology*
  • Neuralgia / etiology
  • Neuralgia / physiopathology*
  • Peripheral Nervous System / drug effects
  • Peripheral Nervous System / injuries
  • Peripheral Nervous System / physiopathology
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / metabolism
  • Receptors, Lysophosphatidic Acid / genetics
  • Receptors, Lysophosphatidic Acid / physiology*
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / injuries
  • Sciatic Nerve / physiopathology
  • Spinal Cord / metabolism
  • Substance P / metabolism*
  • Substance P / pharmacology
  • Substance P / physiology
  • rhoA GTP-Binding Protein / antagonists & inhibitors
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Lysophospholipids
  • Receptors, Lysophosphatidic Acid
  • Substance P
  • Botulinum Toxins
  • rhoA GTP-Binding Protein