SYNTHESIS OF NOVEL NOCICEPTIN ANALOGUES: INVOLVEMENT IN ANALGESIC EFFECTS OF OPIOID AND NITRIC OXIDEERGIC SYSTEMS AFTER COLD STRESS
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2021-01-01
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Abstract
Stress is known to exert an influence on neuroendocrine, autonomic, hormonal, and immune functioning. Various stress models have been reported to induce analgesia. This is a phenomenon, referred to as stress-induced analgesia. Nociceptin and analogues are neuropeptides, neuromodulators, which are able to inhibit the expression of some forms of SIA. Nociceptin/Orphanin FQ(N/OFQ) is a heptadecapeptide which has been found to play a direct role on pain perception. Nitric oxide (NO) plays an important role in initiation and maintenance of pain. It is also known that acute and chronic stresses induce biochemical changes affecting both pain threshold and behaviour. Thus, endogenous opioid peptides and NO, mediated a wide variety of physiological processes including pain transmission and SIA. The aim of the present study was to investigate the effects of novel analogues of N/OFQ(1-13)NH2, where Lysine (Lys) at position 9 and/or 13 was substituted by L-ornithine (Orn) on nociception after cold stress and the involvement of the opioid and nitric oxideergic systems in these effects. Analgesic activity was examined by nociceptive test - pawpressure (PP). All novel analogues of N/OFQ were injected at a dose of 10 p.g kg-1; naloxone (Nal, 1 mg kg-1), JTC-801 (NOP receptor antagonist, 0,5 mg kg-1), NG-nitro-L-arginine methylester (L-NAME, 10 mg kg-1) and L-arginine (L-Arg, 1mg kg-1). All drugs were dissolved in saline and were injected intraperitoneally (i.p.). The nociceptive tests were performed 10 min after peptide injection. Antinociceptive effects were statistically accessed by ANOVA. In conclusion we suggest that in analgesic effects of the novel analogues of nociceptin were involved opioid-, nociceptin- and nitric- oxideergic systems after cold stress.