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Spinal p38β isoform mediates tissue injury‐induced hyperalgesia and spinal sensitization
Author(s) -
Svensson Camilla I.,
Fitzsimmons Bethany,
Azizi Sara,
Powell Henry C.,
Hua XiaoYing,
Yaksh Tony L.
Publication year - 2005
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.1471-4159.2004.02996.x
Subject(s) - spinal cord , gene isoform , nociception , hyperalgesia , sensitization , chemistry , pharmacology , neuroscience , receptor , medicine , biology , biochemistry , gene
Antagonist studies show that spinal p38 mitogen‐activated protein kinase plays a crucial role in spinal sensitization. However, there are two p38 isoforms found in spinal cord and the relative contribution of these two to hyperalgesia is not known. Here we demonstrate that the isoforms are distinctly expressed in spinal dorsal horn: p38α in neurons and p38β in microglia. In lieu of isoform selective inhibitors, we examined the functional role of these two individual isoforms in nociception by using intrathecal isoform‐specific antisense oligonucleotides to selectively block the expression of the respective isoform. In these rats, down‐regulation of spinal p38β, but not p38α, prevented nocifensive flinching evoked by intraplantar injection of formalin and hyperalgesia induced by activation of spinal neurokinin‐1 receptors through intrathecal injection of substance P. Both intraplantar formalin and intrathecal substance P produced an increase in spinal p38 phosphorylation and this phosphorylation (activation) was prevented when spinal p38β, but not p38α, was down‐regulated. Thus, spinal p38β, probably in microglia, plays a significant role in spinal nociceptive processing and represents a potential target for pain therapy.