Drug dependent sex-differences in periaqueducatal gray mediated antinociception in the rat.
Drug dependent sex-differences in periaqueducatal gray mediated antinociception in the rat.
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DOI：
10.1016/j.pain.2009.09.008
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发表时间：
2009-12-15
期刊：
影响因子：
7.4
通讯作者：
Morgan MM
中科院分区：
文献类型：
--
作者：
Bobeck EN;McNeal AL;Morgan MM
μ-阿片受体（MOPr）激动剂，如吗啡，产生更大的抗伤害作用，在雄性大鼠相比，雌性大鼠。腹外侧导水管周围灰质（vlPAG）似乎有助于这种性别差异，尽管较少的vlPAG输出神经元投射到头端腹内侧延髓在男性相比，女性大鼠。雌性大鼠中的这种更大的投射表明，与雄性大鼠相比，vlPAG输出神经元的非阿片样物质激活应在雌性大鼠中产生更大的抗伤害感受。通过比较将MOPr激动剂（吗啡、DAMGO、芬太尼）和非阿片类化合物（荷包牡丹碱、红藻氨酸）微量注射到雌性和雄性大鼠的vlPAG中的时程和抗伤害感受效力来测试该假设。与芬太尼、荷包牡丹碱或红藻氨酸微量注射后产生的镇痛作用（3 min时达到峰值，持续时间小于30 min）相比，吗啡或DAMGO微量注射产生的镇痛作用起效缓慢（15-30 min时达到峰值），持续时间长（60 min）。在时间进程中没有明显的性别差异。当微量注射到vlPAG中时，所有五种化合物引起剂量依赖性抗伤害感受。镇痛效力显着更大的雄性大鼠相比，雌性大鼠微量注射吗啡，DAMGO，荷包牡丹碱，但不微量注射芬太尼或红藻氨酸。与雄性大鼠相比，在任何情况下，vlPAG的激活在雌性大鼠中均不产生更大的抗伤害表位。这些发现表明vlPAG可以在雌性和雄性大鼠中产生相当的抗伤害感受，但是通过抑制GABA能神经元（无论是通过吗啡还是GABAA受体拮抗剂荷包牡丹碱）产生的抗伤害感受在雄性中产生更大的抗伤害感受。
Mu-opioid receptor (MOPr) agonists, such as morphine, produce greater antinociception in male compared to female rats. The ventolateral periaqueductal gray (vlPAG) appears to contribute to this sex difference despite fewer vlPAG output neurons projecting to the rostral ventromedial medulla in male compared to female rats. This greater projection in female rats suggests that non-opioid activation of vlPAG output neurons should produce greater antinociception in female compared to male rats. This hypothesis was tested by comparing the time course and antinociceptive potency of microinjecting MOPr agonists (morphine, DAMGO, fentanyl) and non-opioid compounds (bicuculline, kainic acid) into the vlPAG of female and male rats. Microinjection of morphine or DAMGO produced antinociception that had a slow onset (peak from 15–30 min) and long duration (60 min) compared to the antinociception produced following microinjection of fentanyl, bicuculline, or kainic acid (peak effect at 3 min; duration less than 30 min). No sex-differences in the time courses were evident. All five compounds caused a dose-dependent antinociception when microinjected into the vlPAG. Antinociceptive potency was significantly greater in male compared to female rats following microinjection of morphine, DAMGO, and bicuculline, but not following microinjection of fentanyl or kainic acid. In no case did activation of the vlPAG produce greater antinocicepiton in female compared to male rats. These findings demonstrate that the vlPAG can produce comparable antinociception in female and male rats, but antinociception produced by inhibition of GABAergic neurons (whether by morphine or the GABAA receptor antagonist bicuculline) produces greater antinociception in males.
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