Involvement of LPA1 receptor signaling in cerebral ischemia-induced neuropathic pain

Neuroscience. 2013 Apr 3:235:10-5. doi: 10.1016/j.neuroscience.2013.01.005. Epub 2013 Jan 11.

Abstract

We demonstrated previously that the lysophosphatidic acid-1 (LPA1) receptor plays a crucial role in the initiation of peripheral nerve injury-induced neuropathic pain through the alternation of pain-related genes/proteins expression and demyelination. The present study revealed that mild cerebral ischemia by left transient middle cerebral artery occlusion (tMCAO) for 15min causes the hypersensitive responses (paw withdrawal) to the nociception by electrical stimuli to the paw by the use of Neurometer Current Perception Threshold/C (CPT/C). The hypersensitivity or neuropathic pain was only observed by the stimulation with 250 and 2000, but not 5Hz, which are the characterized sine-wave frequencies of Aδ-, Aβ- or C-fibers, respectively. The significant neuropathic pain was observed from day 2 through week 2 on the right paw after tMCAO, while there was slight but significant pain sensitivity on the left paw at day 7. The neuropathic pain on the contralateral side at week 2 after tMCAO was completely abolished in LPA1(-/-) mice. These results suggest that LPA1 receptor signaling plays key roles in the development of central neuropathic pain following cerebral ischemia as well as the peripheral neuropathic pain following partial sciatic nerve injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology
  • Brain Ischemia / complications*
  • Brain Ischemia / physiopathology*
  • Chronic Pain
  • Electric Stimulation
  • Functional Laterality / physiology
  • Immunohistochemistry
  • Infarction, Middle Cerebral Artery / pathology
  • Infarction, Middle Cerebral Artery / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Fibers / physiology
  • Neuralgia / etiology*
  • Neuralgia / physiopathology*
  • Neuralgia / psychology
  • Pain Measurement
  • Receptors, Lysophosphatidic Acid / genetics
  • Receptors, Lysophosphatidic Acid / physiology*
  • Signal Transduction

Substances

  • Receptors, Lysophosphatidic Acid