Peripheral mechanisms of neuropathic pain - involvement of lysophosphatidic acid receptor-mediated demyelination

Mol Pain. 2008 Apr 1:4:11. doi: 10.1186/1744-8069-4-11.


Recent advances in pain research provide a clear picture for the molecular mechanisms of acute pain; substantial information concerning plasticity that occurs during neuropathic pain has also become available. The peripheral mechanisms responsible for neuropathic pain are found in the altered gene/protein expression of primary sensory neurons. With damage to peripheral sensory fibers, a variety of changes in pain-related gene expression take place in dorsal root ganglion neurons. These changes, or plasticity, might underlie unique neuropathic pain-specific phenotype modifications - decreased unmyelinated-fiber functions, but increased myelinated A-fiber functions. Another characteristic change is observed in allodynia, the functional change of tactile to nociceptive perception. Throughout a series of studies, using novel nociceptive tests to characterize sensory-fiber or pain modality-specific nociceptive behaviors, it was demonstrated that communication between innocuous and noxious sensory fibers might play a role in allodynia mechanisms. Because neuropathic pain in peripheral and central demyelinating diseases develops as a result of aberrant myelination in experimental animals, demyelination seems to be a key mechanism of plasticity in neuropathic pain. More recently, we discovered that lysophosphatidic acid receptor activation initiates neuropathic pain, as well as possible peripheral mechanism of demyelination after nerve injury. These results lead to further hypotheses of physical communication between innocuous Abeta- and noxious C- or Adelta-fibers to influence the molecular mechanisms of allodynia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Demyelinating Diseases / complications*
  • Demyelinating Diseases / physiopathology
  • Humans
  • Hyperalgesia / physiopathology
  • Lysophospholipids / pharmacology
  • Models, Biological
  • Pain / etiology*
  • Pain Measurement
  • Peripheral Nervous System Diseases / complications
  • Peripheral Nervous System Diseases / physiopathology
  • Receptors, Lysophosphatidic Acid / metabolism*
  • Signal Transduction


  • Lysophospholipids
  • Receptors, Lysophosphatidic Acid
  • lysophosphatidic acid