Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Center of Biological Sciences, Londrina State University, Londrina, Paraná, Brazil.
Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Center of Biological Sciences, Londrina State University, Londrina, Paraná, Brazil.
Pharmacol Res. 2020 Jan;151:104549. doi: 10.1016/j.phrs.2019.104549. Epub 2019 Nov 17.
We now appreciate that the mechanism of resolution depends on an active and time-dependent biosynthetic shift from pro-inflammatory to pro-resolution mediators, the so-called specialized pro-resolving lipid mediators (SPMs). These SPMs are biosynthesized from the omega-3 fatty acids arachidonic acid (AA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), or docosahexaenoic acid (DHA). Despite effective for a fraction of patients with rheumatic diseases and neuropathic pain, current analgesic therapies such as biological agents, opioids, corticoids, and gabapentinoids cause unwanted side effects, such as immunosuppression, addiction, or induce analgesic tolerance. A growing body of evidence demonstrates that isolated SPMs show efficacy at very low doses and have been successively used as therapeutic drugs to treat pain and infection in experimental models showing no side effects. Moreover, SPMs work as immunoresolvents and some of them present long-lasting analgesic and anti-inflammatory effects (i.e. block pain without immunosuppressive effects). In this review, we focus on how SPMs block pain, infection and neuro-immune interactions and, therefore, emerge as a new class of non-immunosuppressive and non-opioid analgesic drugs.
我们现在认识到，消退的机制取决于从促炎到促消退介质（所谓的特异性促消退脂质介质，SPM）的积极且随时间变化的生物合成转变。这些 SPM 是从 ω-3 脂肪酸花生四烯酸（AA）、二十碳五烯酸（EPA）、二十二碳五烯酸（DPA）或二十二碳六烯酸（DHA）生物合成的。尽管针对风湿性疾病和神经病理性疼痛的一部分患者有效，但目前的镇痛疗法，如生物制剂、阿片类药物、皮质类固醇和加巴喷丁类药物，会引起免疫抑制、成瘾或诱导镇痛耐受等不良副作用。越来越多的证据表明，分离的 SPM 在非常低的剂量下显示出疗效，并已相继被用作治疗疼痛和感染的治疗药物，在实验模型中没有副作用。此外，SPM 作为免疫调节剂发挥作用，其中一些具有持久的镇痛和抗炎作用（即没有免疫抑制作用的止痛）。在这篇综述中，我们重点关注 SPM 如何阻断疼痛、感染和神经免疫相互作用，因此成为一类新的非免疫抑制和非阿片类镇痛药。
