Silva Rita, Malcangio Marzia
Wolfson Centre for Age-Related Diseases, King's College London, London, United Kingdom.
Front Pain Res (Lausanne). 2021 Jul 27;2:684684. doi: 10.3389/fpain.2021.684684. eCollection 2021.
Injuries to the nervous system can result in a debilitating neuropathic pain state that is often resistant to treatment with available analgesics, which are commonly associated with several side-effects. Growing pre-clinical and clinical evidence over the last two decades indicates that immune cell-mediated mechanisms both in the periphery and in the Central Nervous System (CNS) play significant roles in the establishment and maintenance of neuropathic pain. Specifically, following peripheral nerve injury, microglia, which are CNS resident immune cells, respond to the activity of the first pain synapse in the dorsal horn of spinal cord and also to neuronal activity in higher centres in the brain. This microglial response leads to the production and release of several proinflammatory mediators which contribute to neuronal sensitisation under neuropathic pain states. In this review, we collect evidence demonstrating the critical role played by the Fractalkine/CXCR signalling pathway in neuron-to-microglia communication in neuropathic pain states and explore how strategies that include components of this pathway offer opportunities for innovative targets for neuropathic pain.
神经系统损伤可导致使人衰弱的神经性疼痛状态，这种状态往往对现有镇痛药的治疗有抗性，而这些镇痛药通常伴有多种副作用。过去二十年中越来越多的临床前和临床证据表明，外周和中枢神经系统（CNS）中免疫细胞介导的机制在神经性疼痛的形成和维持中起重要作用。具体而言，在周围神经损伤后，作为CNS驻留免疫细胞的小胶质细胞会对脊髓背角中首个痛觉突触的活动以及大脑中更高中枢的神经元活动作出反应。这种小胶质细胞反应会导致几种促炎介质的产生和释放，这些介质在神经性疼痛状态下会促成神经元致敏。在这篇综述中，我们收集了证据，证明趋化因子/CXCR信号通路在神经性疼痛状态下神经元与小胶质细胞通讯中所起的关键作用，并探讨了包含该通路成分的策略如何为神经性疼痛提供创新靶点的机会。
