LPA5 signaling is involved in multiple sclerosis-mediated neuropathic pain in the cuprizone mouse model

J Pharmacol Sci. 2018 Feb;136(2):93-96. doi: 10.1016/j.jphs.2018.01.001. Epub 2018 Feb 2.


Lysophosphatidic acid (LPA) and LPA1 receptor signaling play a crucial role in the initiation of peripheral nerve injury-induced neuropathic pain through the alternation of pain-related genes/proteins expression and demyelination. However, LPA and its signaling in the brain are still poorly understood. In the present study, we revealed that the LPA5 receptor expression in corpus callosum elevated after the initiation of demyelination, and the hyperalgesia through Aδ-fibers following cuprizone-induced demyelination was mediated by LPA5 signaling. These data suggest that LPA5 signaling may play a key role in the mechanisms underlying neuropathic pain following demyelination in the brain.

Keywords: LPA5; Multiple sclerosis; Neuropathic pain.

MeSH terms

  • Animals
  • Corpus Callosum / metabolism
  • Cuprizone / adverse effects*
  • Disease Models, Animal*
  • Female
  • Gene Expression
  • Lysophospholipids / physiology
  • Male
  • Mice, Inbred Strains
  • Multiple Sclerosis / etiology*
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / metabolism
  • Neuralgia / etiology*
  • Neuralgia / genetics*
  • Receptors, Lysophosphatidic Acid / genetics
  • Receptors, Lysophosphatidic Acid / metabolism
  • Receptors, Lysophosphatidic Acid / physiology*
  • Signal Transduction / physiology*


  • LPAR5 protein, human
  • Lysophospholipids
  • Receptors, Lysophosphatidic Acid
  • Cuprizone
  • lysophosphatidic acid