期刊
JOURNAL OF NEUROCHEMISTRY
卷 102, 期 5, 页码 1658-1668出版社
BLACKWELL PUBLISHING
DOI: 10.1111/j.1471-4159.2007.04796.x
关键词
mitogen-activated protein kinase; platelet-activating factor receptor; primary afferent sensory neurons; tissue injury pain
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-l- mice showed no alterations in spinal pain behaviors caused by intrathecally administering agonists for N- m ethyl- D-aspartate (NMDA) and neurokinin, receptors. A PAFR agonist evoked an intracellular Ca (2+) response predominantly in capsaicin-sensitive DRG neurons, an effect was not observed in pafr-l- mice. By contrast, the PAFR agonist did not affect C- or A delta-evoked excitatory postsynaptic 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据