Effects of oxytocin and oxytocin receptor antagonist atosiban on nociception and morphine analgesia in rats
Abstract
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 μg/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<0,05). Atosiban showed
hyperalgesic activity and decreased the analgesic activity of oxytocin when
given with oxytocin (p<0,05). Oxytocin increased the analgesic activity of
morphine (p<0.05). In addition, although atosiban did not alter the
analgesic activity of morphine, morphine analgesia increased by oxytocin was
reduced (p<0.05).
Conclusions: According to these results, it can be said that although atosiban does
not change on the analgesic effect of morphine alone, it blocks the effect of
oxytocin on morphine analgesia.
References
- 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 streptozotocin-diabetic 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, Martínez-Lorenzana 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, Martínez-Lorenzana 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. Oxytocin-induced 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, Martínez-Lorenzana 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.
Sıçanlarda oksitosin ve oksitosin reseptör antagonisti atosibanın nosisepsiyon ve morfin analjezi üzerine etkileri
Abstract
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 μg/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 <0,05). Atosiban, hiperaljezik
aktivite gösterdi ve oksitosin ile birlikte verildiğinde oksitosin'in analjezik
etkinliğini azalttı (p <0,05). Oksitosin morfinin analjezik etkinliğini
arttırdı (p<0,05). Buna ek olarak, atosiban morfinin analjezik etkinliğini değiştirmese de,
oksitosin ile artmış morfin analjezisini azalttı (p <0.05).
Sonuç:
Bu sonuçlara göre, atosibanın tek başına morfinin analjezik etkisini
değiştirmemesine rağmen, oksitosinin morfin analjezi üzerindeki etkisini bloke
ettiği söylenebilir.
References
- 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 streptozotocin-diabetic 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, Martínez-Lorenzana 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, Martínez-Lorenzana 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. Oxytocin-induced 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, Martínez-Lorenzana 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.
Details
| Subjects | Health Care Administration |
|---|---|
| Journal Section | Basic Science Research Articles |
| Authors | |
| Publication Date | December 18, 2017 |
| Acceptance Date | December 11, 2017 |
| Published in Issue | Year 2017 |