Ahmet Sevki TASKIRAN, Handan GUNES, Ercan OZDEMİR, Gokhan ARSLAN, Berat ERDEM

Effects of oxytocin and oxytocin receptor antagonist atosiban on nociception and morphine analgesia in rats

Amaç: Oksitosin, hipotalamusta supraoptik çekirdek ve paraventrikülerçekirdeklerden salınan, dokuz amino asitten oluşan, peptid yapılı bir hormondur. Oksitosin'in opiyat reseptörleri üzerinde etkili olabileceği gösterilmiştir. Atosiban, oksitosinin reseptör antagonistidir. Bu çalışmada amacımız, oksitosin ve atosibanın nosisepsiyon ve morfin analjezisi üzerine etkilerini araştırmaktır. Yöntem: Çalışmamızda 48 Wistar Albino 230-260 g erkek sıçan kullanıldı. Hayvanlar kontrol, 200 ?g/kg oksitosin, 3 mg/kg atosiban, oksitosin+atosiban, 5 mg/kg morfin, morfin+oksitosin, morfin+ atosiban ve morfin+oksitosin+atosiban olmak üzere sekiz gruba ayrıldı. Kontrol grubuna serum fizyolojik, diğer gruplara belirtilen dozlarda oksitosin ve atosiban intraperitoneal (i.p.) olarak verildi. Morfin, subkütan (s.c.) yoldan verildi. Analjezik etkinliktail flick ve hot plate analjezi testleriyle değerlendirildi. Ortaya çıkan analjezik etki 15., 30., 60., 90. ve 120. dakikalarda ölçüldü ve kaydedidi. Analjezik etkinin değerlendirilmesi % analjezi (MPE) (% analjezi = 100x [ilaç sonrası tepki süresi - ilaç öncesi tepki süresi] / [test kesme süresi - ilaç öncesi tepki süresi] şeklinde formüle edildi. Bulgular: Oksitosin analjezik etkinlik gösterdi (p

Sıçanlarda oksitosin ve oksitosin reseptör antagonisti atosibanın nosisepsiyon ve morfin analjezi üzerine etkileri

Objective: Oxytocin is a peptide-based hormone released from the supraoptic nucleus and paraventricular nucleus in the hypothalamus and consisting of nine amino acids. It has been shown that oxytocin may have an effect on opiate receptors. Atosiban is a oxytocin receptor antagonist. Our aim in this study was to investigate the effects of oxytocin and atosiban on nociception and morphine analgesia. Method: In our study, 48 Wistar Albino 230-260 g male rats were used. The animals were divided into eight groups (control, 200 ?g/kg oxytocin, 3 mg/kg atosiban, oxytocin+ atosiban, 5 mg/kg morphine, morphine+ oxytocin, morphine+atosiban and morphine+ oxytocin+ atosiban). Serum physiologic to the control group, oxytocin and atosiban were given intraperitoneally (i.p.) at the indicated doses to the other groups. Morphine was administered subcutaneously (s.c.). Analgesic effects were assessed by hot plate and tail flick analgesia tests. The resulting analgesic effect was measured and recorded at the 15th, 30th, 60th, 90th and 120th minutes. Assessment of analgesic effect was formulated as % analgesia (MPE) (% analgesia = 100x [post drug reaction time-pre drug reaction time]/ [cut off time-pre drug reaction time]). Results: Oxytocin showed analgesic activity (p

PDF

___

1. Bale TL, Davis AM, Auger AP, Dorsa DM, McCarthy MM. CNS region-specific oxytocin receptor expression: importance in regulation of anxiety and sex behavior. J. Neurosci 2001; 21, 2546-52.
2. Kelly J, Swanson LW. Additional forebrain regions projecting to the posterior pituitary: Preoptic region, bed nucleus of the stria terminalis, and zona incerta. Brain Res 1980; 197: 1-9.
3. Ochedalski T, Subburaju S, Wynn PC, Aguilera G. Interaction between oestrogen and oxytocin on hypothalamic-pituitary- adrenal axis activity. J. Neuroendocrinol 2007; 19, 189-97.
4. Burbach JP, Bohus B, Kovacs GL, Van Nispen JW, Greven HM, De Wied D. Oxytocin is a precursor of potent behaviourally active neuropeptides. Eur. J. Pharmacol 1983; 94, 125-31.
5. Wang JW, Lundeberg T, Yu LC. Antinociceptive role of oxytocin in the nucleus raphe magnus of rats, an involvement of mu-opioid receptor. Regul Pept 2003; 115: 153-9.
6. Gimpl G, Fahrenholz F. The oxytocin receptor system: structure, function, and regulation. Physiol Rev 2001; 81: 629-83. 4.
7. Sanu O, Lamont RF. Critical appraisal and clinical utility of atosiban in the management of preterm labor Clin. Risk Manag 2010; 6, 191.
8. Arletti R, Benelli A, Bertolini A. Influence of oxytocin on nociception and morphine antinociception. Neuropeptides 1993; 24:125- 9.
9. Zubrzycka M, Fichna J, Janecka A. Inhibition of trigemino-hypoglossal reflex in rats by oxytocin is mediated by mu and kappa opioid receptors. Brain Res 2005; 1035:67-72.
10. Ramabadran K, Bansinath M, Turndorf H, Puig MM. The hyperalgesic effect of naloxone is attenuated in streptozotocindiabetic mice. Psychopharmacology (Berl.) 1989; 97, 169-174.
11. Kanaan SA, Saade NE, Haddad JJ, Abdelnoor AM, Atweh SF, Jabbur SJ. Endotoxin-induced local inflammation and hyperalgesia in rats, a new model for inflammatory pain. Pharmacology 1996; 66: 373-9.
12. Yang J, Yang Y, Chen JM, Liu WY, Wang CH, Lin BC. Central oxytocin enhances antinociception in the rat. Peptides 2007; 28: 1113-9.
13. Condés-Lara M, González NM, MartínezLorenzana G, Delgado OL, Freund-Mercier MJ. Actions of oxytocin and interactions with glutamate on spontaneous and evoked dorsal spinal cord neuronal activities. Brain Res 2003; 976: 75-81.
14. Condés-Lara M, Rojas-Piloni G, MartínezLorenzana G, Rodríguez-Jiménez J, López Hidalgo M, Freund-Mercier MJ. Paraventricular hypothalamic influences on spinal nociceptive processing. Brain Res 2006; 1081: 126-37.
15. Schorscher-Petcu A, Sotocinal S, Ciura S, Dupré A, Ritchie J, Sorge RE. Oxytocininduced analgesia and scratching are mediated by the vasopressin-1A receptor in the mouse. J Neurosci 2010; 30: 8274-84.
16. Condés-Lara M1, González NM, MartínezLorenzana G, Delgado OL, Freund-Mercier MJ. Actions of oxytocin and interactions with glutamate on spontaneous and evoked dorsal spinal cord neuronal activities. Brain Res 2003; 976: 75-81.
17. Yu S-Q, Lundeberg T, Yu LC. Involvement of oxytocin in spinal antinociception in rats with inflammation. Brain Res 2003; 983:13-22.
18. Hobo S, Hayashida K, Eisenach JC. Oxytocin inhibits the membrane depolarization-induced increase in intracellular calcium in capsaicin sensitive sensory neurons: a peripheral mechanism of analgesic action. Anesth Analg 2012; 114: 442-9.
19. Wrobel L, Schorscher-Petcu A, Dupré A, Yoshida M, Nishimori K, Tribollet E. Distribution and identity of neurons expressing the oxytocin receptor in the mouse spinal cord. Neurosci Lett 2011; 495: 49-54.
20. Lundeberg T. Oxytocin increases and a specific oxytocin antagonist decreases pain threshold in male rats. Acta Physiol Scand 1992; 144: 487-8.
21. Rojas-Piloni G, López-Hidalgo M, et al. GABA-mediated oxytocinergic inhibition in dorsal horn neurons by hypothalamic paraventricular nucleus stimulation. Brain Res 2007; 1137: 69-77.
22. Condes-Lara M, Maie IA, Dickenson AH. Oxytocin actions on afferent evoked spinal cord neuronal activities in neuropathic but not in normal rats. Brain Res 2005; 1045: 124-33.