Nagakura Yukinori
School of Pharmacy at Fukuoka, International University of Health and Welfare, Fukuoka, Japan
J Pharmacol Exp Ther. 2022 May;381(2):106-119. doi: 10.1124/jpet.121.001051. Epub 2022 Mar 4.
Nociplastic pain, the third category of chronic pain, has emerged as a serious medical issue. Due to its significant negative influences on patients and society, high prevalence, and lack of sufficiently effective treatments, more efficacious therapies are required. This review highlights the potential therapeutic approaches identified in studies that used reserpine-induced myalgia (RIM) animal model that exhibits nociplastic pain-associated phenotypes. These studies have revealed that biologic processes including the chronic reduction of monoamines, increase of oxidative/nitrosative stresses and inflammatory mediators, upregulation of pronociceptive neurotransmitters and their receptors, increase of trophic factors, enhancement of the apoptotic pathway, sensory nerve sensitization, and activation of immune cells in central and/or peripheral regions underly the nociplastic pain-associated phenotypes in RIM animal model. Potential therapeutic approaches to nociplastic pain, i.e., 1) functional modification of specific molecules whose expression is distinctly altered following the chronic reduction of monoamines, 2) targeting the molecules that are responsible for other major categories of chronic pain (i.e., chronic inflammatory pain and neuropathic pain), 3) supplementation of nutrition to correct the disrupted nutritional balance, 4) improvement of physical constitution by natural substances, and 5) nonpharmacological interventions, have been identified. SIGNIFICANCE STATEMENT: Studies in reserpine-induced myalgia (RIM) animal model have revealed the pathologies that occur after the chronic reduction of monoamines and identified potential therapeutic approaches to nociplastic pain. Translation of their analgesic efficacy from RIM animal model to patients remains an issue to be addressed. Successful translation would lead to better therapies for nociplastic pain.
伤害性假性疼痛是慢性疼痛的第三种类别，已成为一个严重的医学问题。由于其对患者和社会具有重大负面影响、患病率高且缺乏足够有效的治疗方法，因此需要更有效的治疗手段。本综述重点介绍了在使用利血平诱导的肌痛（RIM）动物模型的研究中确定的潜在治疗方法，该模型表现出与伤害性假性疼痛相关的表型。这些研究表明，包括单胺慢性减少、氧化/亚硝化应激和炎症介质增加、伤害性感受神经递质及其受体上调、营养因子增加、凋亡途径增强、感觉神经致敏以及中枢和/或外周区域免疫细胞激活在内的生物学过程是RIM动物模型中与伤害性假性疼痛相关表型的基础。已确定了针对伤害性假性疼痛的潜在治疗方法，即：1）对单胺慢性减少后表达明显改变的特定分子进行功能修饰；2）靶向负责其他主要慢性疼痛类别（即慢性炎症性疼痛和神经性疼痛）的分子；3）补充营养以纠正失衡的营养状态；4）通过天然物质改善体质；5）非药物干预。重要声明：利血平诱导的肌痛（RIM）动物模型研究揭示了单胺慢性减少后出现的病理情况，并确定了针对伤害性假性疼痛的潜在治疗方法。将其镇痛效果从RIM动物模型转化到患者身上仍是一个有待解决的问题。成功转化将为伤害性假性疼痛带来更好的治疗方法。
