Gonadal steroid hormone modulation of nociception, morphine antinociception and reproductive indices in male and female rats

Gonadal steroid hormone modulation of nociception, morphine antinociception and reproductive indices in male and female rats
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DOI:
10.1016/s0304-3959(02)00457-8
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发表时间:
2003-06-01
期刊:
影响因子:
7.4
通讯作者:
Craft, RM
Craft, RM
中科院分区:
医学1区
文献类型:
--
作者:
Stoffel, EC;Ulibarri, CM;Craft, RM

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本研究旨在探讨性腺类固醇激素如何调节基础伤害感受和吗啡抗伤害感受,以调节成年大鼠的生殖。雄性和雌性Sprague-Dawley大鼠进行性腺切除(GDX)或假性腺切除(sham); GDX雄性大鼠皮下植入含有睾酮(T)、雌二醇(E2)、双氢睾酮(DHT)、E2和DHT或不含(0)的胶囊。GDX雌性动物在手术后立即接受E2、T或空(0)胶囊,并以4天间隔注射溶媒或孕酮(P4)。手术后28天,在50 ℃和54 ℃热板试验上测试基础伤害感受和吗啡抗伤害感受,此后不久评估生殖行为和生理学。在雄性给药组之间,基线热板给药无显著差异,但吗啡在假手术组和GDX + T雄性中的效力显著高于GDX + 0雄性。T增加吗啡效力的能力与其主要代谢物E2和DHT(一起给药而不是单独给药)近似。间情期期间测试的假雌性动物的基线热板lavage高于发情期期间测试的那些。吗啡是显着更有效的假雌性动物在发情前期和发情间期比在发情期间测试。GDX + E2、GDX + E2/P4和GDX + T雌性动物的基线热板潜伏期显著高于GDX + 0雌性动物,吗啡的效力显著低于GDX + 0雌性动物。在50 ℃热板试验中观察到的基础伤害感受和吗啡抗伤害感受的所有组差异较小,并且在54 ℃热板试验中通常不显著。类固醇操作产生了预期的生殖行为和类固醇敏感器官的变化。这些结果表明,在成年大鼠中,生理相关的性腺类固醇操作调节(1)雌性大鼠的基础伤害感受,但不调节雄性大鼠,以及(2)雄性和雌性大鼠的吗啡抗伤害感受效力。(C)2002年国际疼痛研究协会。由Elsevier Science B. V.出版,版权所有。
The purpose of this study was to examine how gonadal steroid hormones modulate basal nociception and morphine antinociception relative to regulating reproduction in the adult rat. Male and female Sprague-Dawley rats were either gonadectomized (GDX) or sham-gonadectomized (sham); GDX males were implanted subcutaneously with capsules containing testosterone (T), estradiol (E2), dihydrotestosterone (DHT), E2 and DHT, or nothing (0). GDX females received E2, T, or empty (0) capsules immediately after surgery, and vehicle or progesterone (P4) injections at 4-day intervals. Basal nociception and morphine antinociception were tested 28 days after surgery on 50 C and 54 C hotplate tests, and reproductive behavior and physiology were assessed shortly thereafter. There were no significant differences in baseline hotplate latencies among the male treatment groups, but morphine was significantly more potent in sham and GDX + T males than in GDX + 0 males. The ability of T to increase morphine's potency was approximated by its major metabolites E2 and DHT, given together but not alone. Baseline hotplate latencies were higher in sham females tested during diestrus than in those tested during estrus. Morphine was significantly more potent in sham females tested during proestrus and diestrus than in those tested during estrus. Baseline hotplate latencies were significantly higher, and morphine was significantly less potent in GDX + E2, GDX + E2/P4 and GDX + T females than in GDX + 0 females. All group differences in basal nociception and morphine antinociception observed on the 50 C hotplate test were smaller and generally non-significant on the 54 C hotplate test. Steroid manipulations produced the expected changes in reproductive behaviors and steroid-sensitive organs. These results demonstrate that in adult rats, gonadal steroid manipulations that are physiologically relevant, modulate (1) basal nociception in females but not males, and (2) morphine's antinociceptive potency in both males and females. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.