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Reduced pain behaviors and extracellular signal‐related protein kinase activation in primary sensory neurons by peripheral tissue injury in mice lacking platelet‐activating factor receptor
Author(s) -
Tsuda Makoto,
Ishii Satoshi,
Masuda Takahiro,
Hasegawa Shigeo,
Nakamura Koji,
Nagata Kenichiro,
Yamashita Tomohiro,
Furue Hidemasa,
TozakiSaitoh Hidetoshi,
Yoshimura Megumu,
Koizumi Schuichi,
Shimizu Takao,
Inoue Kazuhide
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04796.x
Subject(s) - dorsal root ganglion , nociceptor , peripheral nerve injury , medicine , hyperalgesia , neuroscience , agonist , sensitization , microbiology and biotechnology , chemistry , receptor , sensory system , nociception , biology , sciatic nerve
Abstract Peripheral tissue injury causes the release of various mediators from damaged and inflammatory cells, which in turn activates and sensitizes primary sensory neurons and thereby produces persistent pain. The present study investigated the role of platelet‐activating factor (PAF), a phospholipid mediator, in pain signaling using mice lacking PAF receptor ( pafr− / − mice). Here we show that pafr− / − mice displayed almost normal responses to thermal and mechanical stimuli but exhibit attenuated persistent pain behaviors resulting from tissue injury by locally injecting formalin at the periphery as well as capsaicin pain and visceral inflammatory pain without any alteration in cytoarchitectural or neurochemical properties in dorsal root ganglion (DRG) neurons and a defect in motor function. However, pafr− / − mice showed no alterations in spinal pain behaviors caused by intrathecally administering agonists for N ‐methyl‐ d ‐aspartate (NMDA) and neurokinin 1 receptors. A PAFR agonist evoked an intracellular Ca 2+ response predominantly in capsaicin‐sensitive DRG neurons, an effect was not observed in pafr− / − mice. By contrast, the PAFR agonist did not affect C‐ or Aδ‐evoked excitatory post‐synaptic currents in substantia gelatinosa neurons in the dorsal horn. Interestingly, mice lacking PAFR showed reduced phosphorylation of extracellular signal‐related protein kinase (ERK), an important kinase for the sensitization of primary sensory neurons, in their DRG neurons after formalin injection. Furthermore, U0126, a specific inhibitor of the ERK pathway suppressed the persistent pain by formalin. Thus, PAFR may play an important role in both persistent pain and the sensitization of primary sensory neurons after tissue injury.