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Activation of the nociceptin opioid system in rat sensory neurons produces antinociceptive effects in inflammatory pain: Involvement of inflammatory mediators
Author(s) -
Chen Yong,
Sommer Claudia
Publication year - 2007
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21272
Subject(s) - nociceptin receptor , opioid receptor , hyperalgesia , pharmacology , nociception , medicine , nitric oxide synthase , opioid , receptor , calcitonin gene related peptide , receptor antagonist , allodynia , dorsal root ganglion , spinal cord , nitric oxide , chemistry , opioid peptide , endocrinology , antagonist , neuropeptide , psychiatry
Despite a large body of literature on the nociceptin (NC) opioid system in pain modulation, the mechanism of action of NC remains largely unexplored. Here, we investigated the role and mode of action of the spinal NC system in inflammatory pain. Preemptive intrathecal administration of NC attenuated thermal hyperalgesia and mechanical allodynia in rats with intraplantar complete Freund's adjuvant (CFA) injection. By using immunohistochemistry in L4 dorsal root ganglion (DRG) neurons, a marked increase of NC and ORL1 receptor immunoreactivity was detected following CFA. Intrathecal administration of NC attenuated the CFA‐induced increases of calcitonin gene‐related peptide, transient receptor potential vanilloid‐1, and tumor necrosis factor‐α in DRG neurons. Real‐time reverse transcription‐polymerase chain reaction showed that NC reduced the up‐regulation of inducible nitric oxide synthase mRNA but not that of neuronal nitric oxide synthase mRNA in spinal cord segments after CFA. Furthermore, [Nphe1]NC(1–13)NH2, a selective opioid receptor‐like 1 (ORL1) receptor antagonist, significantly antagonized the effects of NC on pain modulation and on the expression of inflammatory mediators, indicating a specific NC action through the ORL1 receptor. Together, these findings reveal novel mechanisms by which the NC system produces analgesia. © 2007 Wiley‐Liss, Inc.