Involvement of the Nitricoxidergic System in the Analgesic Effects of Newly Synthesized Nociceptin Analogues After Chronic Immobilization Stress

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 (SIA). 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 the initiation and maintenance of pain. It is also known that acute and chronic stress induce biochemical changes affecting both pain threshold and behaviour. Thus, endogenous opioid peptides and NO mediate 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)NH 2 , where lysine (Lys) at position 9 and/or 13 was substituted by L-ornithine (Orn) on nociception after chronic immobilization stress (IS) and the involvement of the nitric oxideergic systems in these effects. Analgesic activity was examined by nociceptive test – paw-pressure (PP). All novel analogues of N/OFQ were injected at a dose of 10 μg/kg, N G -nitro-L-arginine methylester (L-NAME, 10 mg/kg) and L-arginine (L-arg, 1 mg/kg). 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 the nitricoxidergic system after chronic immobilization stress is involved in the analgesic effects of the novel analogues of nociceptin.