Abstract
Purpose: To investigate the analgesic effects of oxytocin (OT) and elucidate the role of dopaminergic system in its mechanisms.Methods: In this study, 72 male (n=6 for each group) 230-250 gr Wistar Albino rats were used. Firstly, dose studies were performed with 100 μg/kg, 200 μg/kg and 400 μg/kg to determine the optimal analgesic effect of oxytocin. Optimal dose was found at 200 μg/kg, and then animals were divided into nine groups: Saline, D1 agonist (SKF 38393; 0.1 mg/kg), D1 antagonist (SCH-23390; 0.1 mg/kg), D1 agonist + oxytocin, D1 antagonist + oxytocin, D2 agonist (Cabergoline; 0,5 mg/kg), D2 antagonist (Sulpride; 10 mg/kg), D2 agonist + oxytocin and D2 antagonist + oxytocin. Serum physiologic saline was given to the saline group and other drugs were administered intraperitoneally at the indicated doses. Tail-flick and hot-plate tests were used to measure analgesic effects. Analgesic tests were measured in 30 min-intervals (at 30th, 60th, 90th, and 120th min) and recorded in seconds. To evaluate maximum antinociceptive effect (% MPE), the tail-flick and hot-plate latencies were converted to the antinociceptive effectivenessResults: The results show that D1 antagonist SCH-23390 (0.1 mg/kg) and D2 agonist cabergoline (0.5 mg/kg) created strong analgesia while the D1 agonist SKF 38393 (0.1 mg/kg) and D2 antagonist sulpiride (10 mg/kg) did not have any analgesic effect. However, only D2 antagonist sulpiride blocked the analgesic effect produced by OTConclusion: OT may be one of the primary agents participating in spinal analgesia, and the dopaminergic system is one of the central mechanisms of action for this important molecule. The dopaminergic system may also be one of the targets for ‘descending’ analgesic system.
 Keywords: Oxytocin, Tail flick, Hot plate, Dopaminergic, Analgesic, Antagonist, Agonist
Highlights
Oxytocin (OT) is an amine peptide synthesized in the paraventricular (PVN) and the supraoptic (SO) nuclei of the hypothalamus
The analgesic effect of oxytocin has been reevaluated in the presence of D1 and D2 receptor agonist and antagonist to elucidate the role of the dopaminergic system in the analgesic effect of oxytocin
Administration of D1 agonist alone did not create any algesic and analgesic effects. It did not have any effect on the analgesic effect of oxytocin
Summary
Oxytocin (OT) is an amine peptide synthesized in the paraventricular (PVN) and the supraoptic (SO) nuclei of the hypothalamus. Activation of GABAergic interneurons, in turn, pre-synaptically inhibits A Delta fiber and C fiber signals at nociceptivespecific and wide-dynamic-range neurons in Laminae I and II [4,5,6]. These effects can be reversed by selective OTR antagonists (d(CH2)5[Tyr(Me), Thr, Tyr-NH29]OVT) [7]. The second potential mechanism linking OT and pain involves an indirect pathway through the endogenous opioid system. Regarding the relationship between OT and endogenous opiates, at least two potential mechanisms exist: OT can stimulate the release of endogenous opioids in the brain [8,9], and OT can bind to ORs and act as an orthosteric agonist or an allosteric modulator
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