Montague Karli, Malcangio Marzia
Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
J Neurochem. 2017 May;141(4):520-531. doi: 10.1111/jnc.13927. Epub 2017 Feb 24.
Chronic pain is a distressing condition, which is experienced even when the painful stimulus, whether surgery or disease related, has subsided. Current treatments for chronic pain show limited efficacy and come with a host of undesirable side-effects, and thus there is a need for new, more effective therapies to be developed. The mechanisms underlying chronic pain are not fully understood at present, although pre-clinical models have facilitated the progress of this understanding considerably in the last decade. The mechanisms underlying chronic pain were initially thought to be neurocentric. However, we now appreciate that non-neuronal cells play a significant role in nociceptive signalling through their communication with neurons. One of the major signalling pathways, which mediates neuron/non-neuronal communication, is chemokine signalling. In this review, we discuss selected chemokines that have been reported to play a pivotal role in the mechanisms underlying chronic pain in a variety of pre-clinical models. Approaches that target each of the chemokines discussed in this review come with their advantages and disadvantages; however, the inhibition of chemokine actions is emerging as an innovative therapeutic strategy, which is now reaching the clinic, with the chemokine Fractalkine and its CX CR receptor leading the way. This article is part of the special article series "Pain".
慢性疼痛是一种令人痛苦的病症，即使疼痛刺激（无论是手术相关还是疾病相关）已经消退，仍会持续存在。目前针对慢性疼痛的治疗效果有限，且伴有许多不良副作用，因此需要开发新的、更有效的疗法。尽管临床前模型在过去十年中极大地促进了对慢性疼痛潜在机制的理解，但目前仍未完全了解其机制。慢性疼痛的潜在机制最初被认为是以神经为中心的。然而，我们现在认识到非神经元细胞通过与神经元的通讯在伤害性信号传导中发挥重要作用。介导神经元/非神经元通讯的主要信号通路之一是趋化因子信号传导。在这篇综述中，我们讨论了在各种临床前模型中被报道在慢性疼痛潜在机制中起关键作用的特定趋化因子。针对本综述中讨论的每种趋化因子的方法都有其优缺点；然而，抑制趋化因子的作用正在成为一种创新的治疗策略，目前已进入临床阶段，趋化因子 fractalkine 及其 CXCR 受体引领了这一进程。本文是“疼痛”专题文章系列的一部分。
