Zhang Shuzhuo, Jin Xu, You Zerong, Wang Shuxing, Lim Grewo, Yang Jinsheng, McCabe Michael, Li Na, Marota John, Chen Lucy, Mao Jianren
MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA Department of Anesthesia and Pain Therapy, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China.
Pain. 2014 Aug;155(8):1504-1515. doi: 10.1016/j.pain.2014.04.026. Epub 2014 May 2.
Anxiety disorder is a comorbid condition of chronic pain. Analgesics and anxiolytics, subject to addiction and abuse, are currently used to manage pain and anxiety symptoms. However, the cellular mechanism underlying chronic pain and anxiety interaction remains to be elucidated. We report that persistent nociception following peripheral nerve injury induced anxiety-like behavior in rodents. Brain expression and release of neuropeptide S (NPS), a proposed endogenous anxiolytic peptide, was diminished in rodents with coexisting nociceptive and anxiety-like behaviors. Intracerebroventricular administration of exogenous NPS concurrently improved both nociceptive and anxiety-like behaviors. At the cellular level, NPS enhanced intra-amygdaloidal inhibitory transmission by increasing presynaptic gamma-aminobutyric acid (GABA) release from interneurons. These findings indicate that the interaction between nociceptive and anxiety-like behaviors in rodents may be regulated by the altered NPS-mediated intra-amygdaloidal GABAergic inhibition. The data suggest that enhancing the brain NPS function may be a new strategy to manage comorbid pain and anxiety.
焦虑症是慢性疼痛的一种共病情况。镇痛药和抗焦虑药存在成瘾和滥用问题，目前用于管理疼痛和焦虑症状。然而，慢性疼痛与焦虑相互作用的细胞机制仍有待阐明。我们报告，外周神经损伤后持续的伤害性感受在啮齿动物中诱发了焦虑样行为。神经肽S（NPS）是一种内源性抗焦虑肽，在同时存在伤害性感受和焦虑样行为的啮齿动物中，其脑内表达和释放减少。脑室内注射外源性NPS同时改善了伤害性感受和焦虑样行为。在细胞水平上，NPS通过增加中间神经元突触前γ-氨基丁酸（GABA）的释放来增强杏仁核内的抑制性传递。这些发现表明，啮齿动物中伤害性感受与焦虑样行为之间的相互作用可能受NPS介导的杏仁核内GABA能抑制改变的调节。数据表明，增强脑内NPS功能可能是管理共病疼痛和焦虑的一种新策略。
