Sex differences in morphine-induced analgesia of visceral pain are supraspinally and peripherally mediated
Sex differences in morphine-induced analgesia of visceral pain are supraspinally and peripherally mediated
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DOI：
10.1152/ajpregu.00824.2005
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发表时间：
2006-08-01
影响因子：
2.8
通讯作者：
Traub, Richard J.
中科院分区：
文献类型：
--
作者：
Ji, Yaping;Murphy, Anne Z.;Traub, Richard J.
越来越多的证据表明，对躯体组织疼痛的阿片类镇痛存在性别差异。然而，在内脏疼痛和阿片类镇痛中是否存在性别差异尚不清楚。本研究在内脏疼痛的结肠膨胀（CRD）模型中检验了这一点。记录了性腺完整的雄性和雌性大鼠对有毒CRD的内脏运动反应（vmr）。吗啡皮下注射剂量依赖性地降低两组vmr，但不影响结肠顺应性。然而，吗啡对雄性大鼠的作用明显强于雌性大鼠。由于全身吗啡可作用于外周组织和中枢神经系统（CNS），因此确定了吗啡镇痛的性别差异来源。外周限制性多阿片受体（MOR）拮抗剂纳洛酮可剂量依赖性地减弱全身吗啡的作用。外周限制性MOR激动剂洛哌丁胺的全身给药证实了外周介导的吗啡镇痛作用，并显示男性比女性更有效。脊髓注射吗啡剂量依赖性减弱vmr，但无性别差异。在雄性大鼠中，脑室内注射吗啡也有剂量依赖性地减弱vmr。本研究记录了吗啡镇痛对外周和棘上介导的内脏疼痛的性别差异。
Increasing evidence suggests there is a sex difference in opioid analgesia of pain arising from somatic tissue. However, the existence of a sex difference in visceral pain and opioid analgesia is unclear. This was examined in the colorectal distention (CRD) model of visceral pain in the current study. The visceromotor response (vmr) to noxious CRD was recorded in gonadally intact male and female rats. Subcutaneous injection of morphine dose-dependently decreased the vmr in both groups without affecting colonic compliance. However, morphine was significantly more potent in male rats than females. Because systemic morphine can act at peripheral tissue and in the central nervous system (CNS), the source of the sex difference in morphine analgesia was determined. The peripherally restricted mu-opioid receptor (MOR) antagonist naloxone methiodide dose-dependently attenuated the effects of systemic morphine. Systemic administration of the peripherally restricted MOR agonist loperamide confirmed peripherally mediated morphine analgesia and revealed greater potency in males compared with females. Spinal administration of morphine dose-dependently attenuated the vmr, but there was no sex difference. Intracerebroventricular administration of morphine also dose-dependently attenuated the vmr with significantly greater potency in male rats. The present study documents a sex difference in morphine analgesia of visceral pain that is both peripherally and supraspinally mediated.