Elsevier

Neuroscience Letters

Volume 223, Issue 2, 21 February 1997, Pages 113-116
Neuroscience Letters

Spinal analgesic activity of orphanin FQ/nociceptin and its fragments

https://doi.org/10.1016/S0304-3940(97)13414-0Get rights and content

Abstract

Previous work reveals that orphanin FQ/nociceptin (OFQ/N) administered supraspinally produces an initial hyperalgesic response followed by analgesia. Spinally, OFQ/N elicits a rapidly appearing, naltrexone-reversible, dose-dependent analgesia in the tailflick assay without any indication of hyperalgesia. Two OFQ/N fragments, OFQ/N (1–7) and OFQ/N (1–11), are active, but far weaker. Blockade of sigma receptors with haloperidol enhances the analgesic potency of spinal OFQ/N, OFQ/N (1–7) and OFQ/N (1–11), but not as dramatically as supraspinal OFQ. Antisense probes targeting the second and third coding exons, but not the first exon, of the cloned mouse OFQ/N receptor (KOR-3) partially block OFQ/N analgesia.

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Acknowledgements

We thank Drs. J. Posner and R. Rapaka for their assistance with these studies. This work was supported, in part, by the National Institute on Drug Abuse by a research grant (DA07242) and a Research Scientist Award (DA00220) to G.W.P. and a Research Scientist Development Award (DA00310) to G.C.R.

References (30)

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    The mRNA for NOP receptor was also found in the dorsal spinal cord (Bunzow et al., 1994; Wick et al., 1995), suggesting an important role for N/OFQ–NOP receptor system in the modulation of nociceptive signals at spinal level. N/OFQ was reported to induce behavioral responses (Sakurada et al., 1999b), allodynia and thermal hyperalgesia in conscious mice (Hara et al., 1997; Sakurada et al., 1999a), facilitate the flexor reflex (Xu et al., 1996) at low doses, and produce analgesia (King et al., 1997; Nazzaro et al., 2007; Xu et al., 1996), anti-hyperalgesic and anti-allodynic effects (Hao et al., 1998) at high doses. In the present study, we have observed that intrathecal [Tyr6] γ2-MSH(6-12) elicited hyperalgesia as assayed by tail withdrawal test and nociceptive behavioral responses including biting, licking and scratching in mice.

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