STUDY OF EFFECTS OF NEWLY SYNTHESISED NOCICEPTIN ANALOGUES ON THE ENDOCANNABINOID SYSTEM AND PAIN AFTER CHRONIC IMMOBILIZATION STRESS
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2023-01-01
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Abstract
Stress provokes stress-induced analgesia (SIA), which depends on an opioid and non-opioid components. The non-opioid one comprises several systems among which are endocannabinoid (ECS), adrenergic, and nitricoxidergic participating in the descending antinociceptive system of the body. The ECS system has a well-established role in the modulation of pain perception and behavioral responses after stress. Nociceptin/Orphanin FQ(N/OFQ) is a heptadecapeptide that has been found to play a role in pain perception. This study aimed to investigate the effects of novel nociceptin N/OFQ(1-13)NH2 analogues on nociception after chronic immobilization stress (CIS) and the involvement of the ECS in analgesic effects. The experiments were carried out on male Wistar rats. The animals were immobilized in a tube for 3 hours daily for 4 days. Analgesic effects were examined by the paw-pressure (PP) test. All novel analogues of N/OFQ(1-13)NH2, the cannabinoid receptor type 1 (СВ1-receptor) agonist N-arachidonoylethanolamide (AEA), and the СВ1-receptors antagonist N-(Piperidin-1-yl)-5-(4-iodophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AМ251) were administered intraperitoneally (i.p) dissolved in Dimethyl sulfoxide (DMSO). Statistical analysis was performed using one-way ANOVA. The results showed that nociceptin and analogues administered after CIS decreased the pain threshold significantly compared to a group that underwent chronic stress only. The administration of AEA immediately after the end of stress led to a significantly increased pain threshold, while administration of AM251 significantly decreased the pain threshold versus the both control and group that underwent chronic stress only. Nociceptin and analogues co-administered with СВ1-receptor agonist (AEA) or antagonist (AM251) after the end of stress decreased immobilization SIA. Our study gives us reason to assume the participation of ECS in the analgesic effects of the novel nociceptin analogues after chronic immobilization stress.