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经全身给药的催产素对大鼠有镇痛作用吗?

Is systemically administered oxytocin an analgesic in rats?

作者信息

Xiao-Jun Xu, Wiesenfeld-Hallin Zsuzsanna

机构信息

Department of Clinical Physiology, Section of Clinical Neurophysiology, Huddinge University Hospital, Karolinska Institute, S-141 86 HuddingeSweden.

出版信息

Pain. 1994 May;57(2):193-196. doi: 10.1016/0304-3959(94)90223-2.

DOI:10.1016/0304-3959(94)90223-2
PMID:8090516
Abstract

The effect of systemically administered oxytocin and a specific oxytocin antagonist, 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin, on heat pain sensitivity was examined in rats. Intraperitoneal (i.p.) oxytocin at 1 mg/kg, but not at 0.1 and 0.3 mg/kg, significantly increased response latencies on the hot-plate test. However, the rats displayed clear signs of sedation, motor impairment and vasoconstriction after 1 mg/kg oxytocin. Skin temperature on the plantar surface of the hind paws was also significantly decreased by this dose of oxytocin. The oxytocin antagonist (1 mg/kg i.p.) did not influence response latency. Since increased response latency was not the only behavioral effect of oxytocin, we conducted electrophysiological experiments to examine the effect of systemic oxytocin on the nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats. Oxytocin at 0.1 mg/kg i.p. did not influence flexor reflex magnitude, mean blood pressure or heart rate. Oxytocin at 0.3 and 1 mg/kg caused a gradual increase in blood pressure with stronger effect observed with 1 mg/kg. Neither 0.3 nor 1 mg/kg oxytocin significantly influenced the flexor reflex magnitude and heart rate. We thus conclude that systemic oxytocin did not produce analgesia in rats and the observed increase in response latency in the hot-plate test may result from the sedative and vasoconstrictive effects of this peptide. Furthermore, since the oxytocin antagonist did not significantly alter response latency on the hot-plate test, it is unlikely that endogenous oxytocin exerts a tonic effect on the pain threshold in rats.

摘要

在大鼠中研究了全身给药的催产素和一种特定的催产素拮抗剂1-脱氨基-2-D-酪氨酸(乙酯)-4-苏氨酸-8-鸟氨酸催产素对热痛敏感性的影响。腹腔注射(i.p.)1mg/kg的催产素可显著增加热板试验中的反应潜伏期,但0.1mg/kg和0.3mg/kg剂量则无此作用。然而,1mg/kg催产素给药后,大鼠出现明显的镇静、运动障碍和血管收缩迹象。该剂量的催产素还显著降低了后爪足底表面的皮肤温度。催产素拮抗剂(1mg/kg i.p.)对反应潜伏期无影响。由于反应潜伏期增加并非催产素的唯一行为效应,我们进行了电生理实验,以研究全身给予催产素对去大脑、脊髓横断、未麻醉大鼠伤害性屈肌反射的影响。腹腔注射0.1mg/kg的催产素对屈肌反射幅度、平均血压或心率无影响。腹腔注射0.3mg/kg和1mg/kg的催产素可使血压逐渐升高,1mg/kg时作用更强。0.3mg/kg和1mg/kg的催产素均未显著影响屈肌反射幅度和心率。因此,我们得出结论,全身给予催产素在大鼠中不会产生镇痛作用,热板试验中观察到的反应潜伏期增加可能是该肽的镇静和血管收缩作用所致。此外,由于催产素拮抗剂在热板试验中未显著改变反应潜伏期,内源性催产素不太可能对大鼠的痛阈产生紧张性作用。

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Body temperature and cardiac changes induced by peripherally administered oxytocin, vasopressin and the non-peptide oxytocin receptor agonist WAY 267,464: a biotelemetry study in rats.外周给予催产素、血管加压素和非肽催产素受体激动剂 WAY 267,464 引起的体温和心脏变化:大鼠生物遥测研究。
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Oxytocin inhibits the membrane depolarization-induced increase in intracellular calcium in capsaicin sensitive sensory neurons: a peripheral mechanism of analgesic action.
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Analgesic effect of intrathecally administered orexin-A in the rat formalin test and in the rat hot plate test.鞘内注射食欲素-A在大鼠福尔马林试验和大鼠热板试验中的镇痛作用。
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