一种向益乳素的抗体,以防止压力诱导的外周感受器敏感化和女性手术后疼痛
Harrison J Stratton1, Mahdi Dolatyari1, Carol Kopruszinski1
1Department of Pharmacology, University of Arizona, Tucson, AZ 85724.
概括
压力会加剧手术后的疼痛,特别是在女性身上,通过使神经细胞敏感. 一种新的向益生菌的抗体 (PRL) 显示出它有望预防女性的这种压力诱导的疼痛过敏.
科学领域:
- 神经科学是一个神经科学.
- 疼痛研究 疼痛研究
- 内分泌学 在内分泌学.
背景情况:
- 手术前的压力和焦虑是导致长期术后疼痛的危险因素,特别是在女性身上.
- 连接心理压力和女性手术后疼痛增加的潜在机制尚未完全理解.
- 益生素 (PRL) 是一种神经激素,受压力和雌激素的影响,在感觉中起作用.
研究的目的:
- 为了研究这种假设,压力使背根结节 (DRG) 感受器敏感,从而放大术后疼痛.
- 探索益生菌及其受体异型 (PRLR-L和PRLR-S) 在压力诱导的疼痛过敏中所起的作用.
- 评估向益乳素治疗女性手术后疼痛的治疗潜力.
主要方法:
- 在雄性和雌性小鼠中使用了束应力 (RS) 和切口伤害模型.
- 研究了压力和损伤对PRLR-L和PRLR-S表达和恶感受体刺激性的影响.
- 使用药理抑制 pituitary PRL,基因操纵 (PRLR-L过度表达,CRISPR/Cas9编辑),以及针对人类PRL (hPRL) 的单克隆抗体 (PL200,019).
- 在人类雌性 nociceptors 和表达hPRL的雌性小鼠中测试了PL200,019.
主要成果:
- 克制压力在两性中都加剧了切口伤害引起的疼痛过敏,女性的影响更为明显.
- 在女性中,压力和受伤导致PRLR-L下降,并增加了PRL依赖的感受器刺激性.
- 针对PRL信号的药理和遗传干预选择性抑制了女性的术后疼痛过敏.
- 反PRL抗体PL200,019有效地阻止了人类雌性 nociceptors的hPRL诱导的敏感化,并防止了表达hPRL的小鼠的过敏.
结论:
- 通过PRLR-S介导的益生菌信号传递的DRG nociceptors的压力诱导的敏感化是女性放大术后疼痛的关键机制.
- 用单克隆抗体向益乳素提供了一种潜在的策略,可以预防性地抑制压力诱导的感应器敏感化.
- 这种方法可以改善女性的术后疼痛管理,减少阿片类药物依赖,并减轻慢性疼痛发展的风险.
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