Effect of intrathecal nocistatin on nociceptin/orphanin FQ analgesia in chronic constriction injury rat.
Nocistatin and nociceptin/orphanin FQ (N/OFQ) are two neuropeptides derived from the same precursor protein, prepronociceptin (ppOFQ), and exhibit different effects on spinal neurotransmission. Nocistatin does not bind to nociceptin/orphanin FQ peptide receptor (NOP), but intrathecal (i.t.) nocistatin has been reported to block the analgesic effect of i.t. N/OFQ. In this study, we investigated the effect of i.t. nocistatin on N/OFQ analgesia to radiant thermal stimuli in chronic constriction injury (CCI) rat. Firstly, to investigate the analgesic effect of N/OFQ, different doses of N/OFQ (3, 10, 30 microg) were intrathecally injected and foot withdrawal latency (FWL) to radiant heat was recorded. It is observed that 3 microg N/OFQ had no effect on FWL, 10 and 30 microg N/OFQ significantly increased FWL of CCI rat. Then, 10 microg N/OFQ, 10 microg nocistatin and a drug cocktail including 10 microg N/OFQ and 10 microg nocistatin were intrathecally injected. The results showed that FWL significantly decreased after using N/OFQ and nocistatin compared with using only N/OFQ, and 10 microg nocistatin had no effect on FWL versus control, suggesting that this dose of nocistatin per se had no effect on the pain threshold of CCI rat, but could block the analgesic effect of N/OFQ. These results indicated that i.t. N/OFQ dose-relatedly depressed thermal hyperalgesia produced by CCI and nocistatin could block N/OFQ analgesia at spinal level in CCI rat.
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D003251:Constriction, Pathologic; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D007278:Injections, Spinal; D008297:Male; D018847:Opioid Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000187:drug effects* / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists*; D012584:Sciatic Nerve / Q000293:injuries; D013997:Time Factors; D000097629:Nociceptin
D000701:Analgesics, Opioid; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000097629:Nociceptin; C111148:nocistatin