Pola Pietro, Frezza Alessia, Gavioli Elaine C, Calò Girolamo, Ruzza Chiara
Department of Neuroscience and Rehabilitation, University of Ferrara, 44121 Ferrara, Italy.
Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal 59078-900, Brazil.
Brain Sci. 2024 Sep 19;14(9):936. doi: 10.3390/brainsci14090936.
Exposure to physical and psychological stress modulates pain transmission in a dual manner. Stress-induced analgesia (SIA) refers to the reduction in pain sensitivity that can occur in response to acute stress. On the contrary, chronic stress exposure may lead to a phenomenon named stress-induced hyperalgesia (SIH). SIH is a clinically relevant phenomenon since it has been well documented that physical and psychological stress exacerbates pain in patients with several chronic pain syndromes, including migraine. The availability of animal models of SIA and SIH is of high importance for understanding the biological mechanisms leading to these phenomena and for the identification of pharmacological targets useful to alleviate the burden of stress-exacerbated chronic pain. Among these targets, the nociceptin/orphanin FQ (N/OFQ)-N/OFQ peptide (NOP) receptor system has been identified as a key modulator of both pain transmission and stress susceptibility. This review describes first the experimental approaches to induce SIA and SIH in rodents. The second part of the manuscript summarizes the scientific evidence that suggests the N/OFQ-NOP receptor system as a player in the stress-pain interaction and candidates NOP antagonists as useful drugs to mitigate the detrimental effects of stress exposure on pain perception.
暴露于生理和心理应激会以双重方式调节疼痛传递。应激诱导的镇痛（SIA）是指因急性应激而发生的痛觉敏感性降低。相反，长期暴露于应激可能会导致一种名为应激诱导的痛觉过敏（SIH）的现象。SIH是一种与临床相关的现象，因为已有充分的文献证明，生理和心理应激会加重包括偏头痛在内的几种慢性疼痛综合征患者的疼痛。SIA和SIH动物模型的可用性对于理解导致这些现象的生物学机制以及确定有助于减轻应激加剧的慢性疼痛负担的药理学靶点非常重要。在这些靶点中，孤啡肽/孤啡肽FQ（N/OFQ）-N/OFQ肽（NOP）受体系统已被确定为疼痛传递和应激易感性的关键调节因子。本综述首先描述了在啮齿动物中诱导SIA和SIH的实验方法。本文的第二部分总结了科学证据，这些证据表明N/OFQ-NOP受体系统在应激-疼痛相互作用中发挥作用，并表明NOP拮抗剂有望作为减轻应激暴露对疼痛感知的有害影响的有用药物。
