Sex Differences in a Rat Model of Peripheral Neuropathic Pain and Associated Levels of Endogenous Cannabinoid Ligands.
Sex Differences in a Rat Model of Peripheral Neuropathic Pain and Associated Levels of Endogenous Cannabinoid Ligands.
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DOI：
10.3389/fpain.2021.673638
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Llorente-Berzal Á
中科院分区：
文献类型：
--
作者：
Boullon L;Finn DP;Llorente-Berzal Á
慢性神经性疼痛是一种主要的未满足的临床需求，影响了10%的世界人口，其中大多数患有共病情绪障碍。据报道，在疼痛患病率、感知和对镇痛药的反应方面存在性别差异。然而，慢性神经病理性疼痛中的两性异形和相关的神经生物学仍然知之甚少。与目前的药物治疗相关的疗效和不良反应的缺乏进一步强调了对新的治疗靶点的需求。内源性大麻素系统（ECS）是一种脂质信号传导系统，调节大量的生理过程，包括疼痛。本研究的目的是调查性二态性疼痛，焦虑和抑郁相关的行为，并伴随改变脊髓和脊髓内源性大麻素水平的备用神经损伤（SNI）周围神经性疼痛的动物模型。在成年雄性和雌性Sprague-Dawley大鼠中进行假手术或SNI手术。每周分别使用von Frey和丙酮跌落试验测试机械和冷异常性疼痛。抑郁相关行为的发展进行了分析，使用蔗糖飞溅和蔗糖偏好测试。采用旷场和高架十字迷宫试验评估自发活动和焦虑相关行为。在手术后42天，对下行抑制性疼痛通路的脊髓上区域和脊髓中的内源性大麻素配体和相关N-酰基乙醇胺的水平进行了分析。SNI手术在两种性别的大鼠中诱导异常性疼痛。女性SNI大鼠表现出更早的发病和更大的敏感性冷和机械异常性疼痛比他们的男性同行。与假手术对照组相比，SNI诱导雄性大鼠直立显著减少。SNI手术后观察到女性抑郁样行为和男性焦虑样行为的趋势，但未达到统计学显著性。内源性大麻素配体和相关的N-酰基乙醇胺的水平没有伴随的变化，在分析的区域观察。我们的研究结果表明，SNI诱导的伤害性行为的雄性和雌性大鼠之间的差异发展，这表明重要的性二态性修改疼痛通路。SNI对任何性别动物的抑郁或焦虑相关行为没有影响，也没有影响在研究的时间点参与伤害性感受下行调制的区域的内源性大麻素配体和相关N-酰基乙醇胺的水平。
Chronic neuropathic pain is a major unmet clinical need affecting 10% of the world population, the majority of whom suffer from co-morbid mood disorders. Sex differences have been reported in pain prevalence, perception and response to analgesics. However, sexual dimorphism in chronic neuropathic pain and the associated neurobiology, are still poorly understood. The lack of efficacy and the adverse effects associated with current pharmacological treatments, further underline the need for new therapeutic targets. The endocannabinoid system (ECS) is a lipid signalling system which regulates a large number of physiological processes, including pain. The aim of this study was to investigate sexual dimorphism in pain-, anxiety- and depression-related behaviours, and concomitant alterations in supraspinal and spinal endocannabinoid levels in the spared nerve injury (SNI) animal model of peripheral neuropathic pain. Sham or SNI surgery was performed in adult male and female Sprague-Dawley rats. Mechanical and cold allodynia was tested weekly using von Frey and acetone drop tests, respectively. Development of depression-related behaviours was analysed using sucrose splash and sucrose preference tests. Locomotor activity and anxiety-related behaviours were assessed with open field and elevated plus maze tests. Levels of endocannabinoid ligands and related N-acylethanolamines in supraspinal regions of the descending inhibitory pain pathway, and spinal cord, were analysed 42 days post-surgery. SNI surgery induced allodynia in rats of both sexes. Female-SNI rats exhibited earlier onset and greater sensitivity to cold and mechanical allodynia than their male counterparts. In male rats, SNI induced a significant reduction of rearing, compared to sham controls. Trends for depressive-like behaviours in females and for anxiety-like behaviours in males were observed after SNI surgery but did not reach statistical significance. No concomitant alterations in levels of endogenous cannabinoid ligands and related N-acylethanolamines were observed in the regions analysed. Our results demonstrate differential development of SNI-induced nociceptive behaviour between male and female rats suggesting important sexually dimorphic modifications in pain pathways. SNI had no effect on depression- or anxiety-related behaviours in animals of either sex, or on levels of endocannabinoid ligands and related N-acylethanolamines across the regions involved in the descending modulation of nociception at the time points investigated.
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