Browsing by Author "Himcheva I."

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    Involvement of the opioidergic and nociceptinergic systems in the analgesic effects of novel nociceptin analogues after acute and chronic immobilization stress
    (2022-01-01) Himcheva I.; Stavreva G.T.; Naydenova E.; Bocheva A.
    Stress is known to exert an influence on neuroendocrine, autonomic, hormonal functioning. Various stress models have been reported to induce analgesia. This is a phenomenon, referred to as stress-induced analgesia (SIA). Nociceptin/Orphanin FQ(N/OFQ) is a heptadecapeptide that has been found to play a direct role on pain perception. This study aimed to investigate the effects of novel nociceptin analogues on nociception after acute and chronic immobilization stress (CIS) and the involvement of the opioid and nociceptinergic systems in analgesic effects. Analgesic effects were examined by paw-pressure (PP) and hot-plate (HP) tests. Our data showed that acute immobilization stress induced hypoalgesia. The analgesic effect was more pronounced in pain caused by a mechanical stimulus than by a thermal one. CIS attenuated the hyperalgesic effect of naloxone and JTC-801 for mechanical and thermal stimulation. The effects of the opioid system are more pronounced in acute immobilization stress, while the nociceptin mechanisms predominate after chronic stress.
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    STUDY OF EFFECTS OF NEWLY SYNTHESISED NOCICEPTIN ANALOGUES ON THE ENDOCANNABINOID SYSTEM AND PAIN AFTER CHRONIC IMMOBILIZATION STRESS
    (2023-01-01) Himcheva I.; Stavreva G.; Naydenova E.; Bocheva A.
    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.
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    SYNTHESIS OF NOVEL NOCICEPTIN ANALOGUES: INVOLVEMENT IN ANALGESIC EFFECTS OF OPIOID AND NITRIC OXIDEERGIC SYSTEMS AFTER COLD STRESS
    (2021-01-01) Himcheva I.; Angelova N.; Naydenova E.; Stavreva G.; Krastev D.; Kochev D.; Bocheva A.
    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.