Activation of the nociceptin opioid system in rat sensory neurons produces antinociceptive effects in inflammatory pain: involvement of inflammatory mediators.
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-alpha 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.
Chen
Yong
Y
Department of Neurology, University of Würzburg, Würzburg, Germany. chen_y@klinik.uni-wuerzburg.de
Sommer
Claudia
C
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D007278:Injections, Spinal; D008159:Lumbar Vertebrae; D008297:Male; D009475:Neurons, Afferent / Q000378:metabolism*; D018847:Opioid Peptides / Q000008:administration & dosage / Q000502:physiology*; D017288:Pain Threshold / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D015740:Calcitonin Gene-Related Peptide; D018836:Inflammation Mediators; D018847:Opioid Peptides; D011957:Receptors, Opioid; D050916:TRPV Cation Channels; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat