nocistatin and Constriction--Pathologic

Nociceptin/orphanin FQ (N/OFQ) and nocistatin are derived from the same precursor peptide, prepronociceptin. N/OFQ and nocistatin have been postulated to participate in pain modulation. In this study, we investigated whether the prepronociceptin, N/OFQ and nocistatin concentrations in the brain and spinal cord would be altered in chronic constriction injury and diabetic rat neuropathic pain models. Total brain and spinal cord lysates as well as serum from rats that had undergone chronic constriction injury and streptozocin-induced diabetic neuropathy were used to determine the concentrations of three peptides using competitive radioimmunoassay. We found that N/OFQ and prepronociceptin concentrations were significantly raised in both rat neuropathic pain models. Nocistatin was raised in the brains of post traumatic neuropathy pain rats. Overall, our data have demonstrated for the first time that prepronociceptin, N/OFQ and nocistatin concentrations are significantly altered at different tissues of two rat neuropathy pain models.

Topics: Animals; Brain; Constriction, Pathologic; Diabetic Neuropathies; Disease Models, Animal; Gene Expression Regulation; Nociceptin; Opioid Peptides; Protein Precursors; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Spinal Cord; Streptozocin; Time Factors

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.

Topics: Analgesics, Opioid; Animals; Constriction, Pathologic; Dose-Response Relationship, Drug; Hot Temperature; Injections, Spinal; Male; Nociceptin; Opioid Peptides; Pain; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Sciatic Nerve; Time Factors