Bradshaw Heather B, Rimmerman Neta, Krey Jocelyn F, Walker J Michael
Department of Psychological and Brain Sciences, Indiana University, 1101 East 10th St., Bloomington, IN 47405, USA.
Am J Physiol Regul Integr Comp Physiol. 2006 Aug;291(2):R349-58. doi: 10.1152/ajpregu.00933.2005. Epub 2006 Mar 23.
One important function of endocannabinoids and related lipid mediators in mammalian central nervous system is modulation of pain. Evidence obtained during the last decade shows that altered levels of these compounds in the brain accompany decreases in pain sensitivity. Such changes, if sexually dimorphic, could account for sex differences in pain and differences that occur during different phases of the hormonal cycle in females. To examine this possibility, we measured the levels of the pain-modulatory lipids anandamide, 2-arachidonoyl glycerol, N-arachidonoyl glycine, N-arachidonoyl gamma amino butyric acid, and N-arachidonoyl dopamine in seven different brain areas (pituitary, hypothalamus, thalamus, striatum, midbrain, hippocampus, and cerebellum) in male rats, and in female rats at five different points in the estrous cycle. The cerebellum did not demonstrate a change in endocannabinoid production across the estrous cycle, whereas all other areas tested showed significant differences in at least one of the compounds measured. These changes in levels occurred predominantly within the 36-h time period surrounding ovulation and behavioral estrus. Differences between males and females were measured as either estrous cycle-independent (all estrous cycles combined) or cycle-dependent (comparisons of males to each estrous cycle). In cycle-independent analyses, small sex differences were observed in the pituitary, hypothalamus, cerebellum, and striatum, whereas no differences were observed in the thalamus, midbrain, and hippocampus. In cycle-dependent analyses, the hypothalamus and pituitary showed largest sex differences followed by the striatum, midbrain, and hippocampus, whereas no sex differences were measured in thalamus and cerebellum. These data provide a basis for investigations into how differences in sex and hormonal status play a role in mechanisms regulating endocannabinoid production and pain.
内源性大麻素及相关脂质介质在哺乳动物中枢神经系统中的一个重要功能是对疼痛的调节。过去十年间获得的证据表明，大脑中这些化合物水平的改变伴随着疼痛敏感性的降低。如果这些变化存在性别差异，那么这可能解释了疼痛方面的性别差异以及雌性激素周期不同阶段出现的差异。为了探究这种可能性，我们测量了雄性大鼠以及处于发情周期五个不同时间点的雌性大鼠七个不同脑区（垂体、下丘脑、丘脑、纹状体、中脑、海马体和小脑）中疼痛调节脂质花生四烯乙醇胺、2-花生四烯酸甘油酯、N-花生四烯酰甘氨酸、N-花生四烯酰γ-氨基丁酸和N-花生四烯酰多巴胺的水平。小脑在整个发情周期内未表现出内源性大麻素产生的变化，而所有其他测试区域至少在一种被测化合物上显示出显著差异。这些水平变化主要发生在排卵和行为发情前后的36小时时间段内。雄性和雌性之间的差异被测量为发情周期无关（所有发情周期合并）或周期相关（雄性与每个发情周期的比较）。在与发情周期无关的分析中，在垂体、下丘脑、小脑和纹状体中观察到了小的性别差异，而在丘脑、中脑和海马体中未观察到差异。在与发情周期相关的分析中，下丘脑和垂体表现出最大的性别差异，其次是纹状体、中脑和海马体，而在丘脑和小脑中未测量到性别差异。这些数据为研究性别和激素状态差异如何在调节内源性大麻素产生和疼痛的机制中发挥作用提供了基础。
