Bingham Brendan, Ajit Seena K, Blake David R, Samad Tarek A
Wyeth Research, Princeton, NJ 08543-8000, USA.
Nat Clin Pract Rheumatol. 2009 Jan;5(1):28-37. doi: 10.1038/ncprheum0972.
Nociceptive pain in response to peripheral noxious stimuli, and inflammatory pain resulting from tissue damage, serve as warnings that normal bodily function cannot resume until the stimulus abates or the tissue repairs. Stimuli cause numerous receptors, ion channels and other cellular machinery to respond, and propagate signals to the central nervous system, where this information is processed and perceived as pain. In healthy individuals, tissue damage results in physiologic--generally reparative--changes that lead to heightened sensory perception and, often, pain. In rheumatic diseases, the joint pain bears much in common with chronic inflammatory pain, but the underlying disease state is typically much more intricate and no reparative function is evident. Addressing the complex pains of rheumatic disease remains an ongoing challenge. Pain signaling pathways involve many molecular components that could potentially be targets for pharmacotherapeutic intervention, but the complexity of this system might also mean that multiple sites must be affected simultaneously to disrupt propagation of pain signals. In addition, to be therapeutically viable, pain drugs must be safe and not alter tactile sensory function, alertness or cognitive function. In this article we review the molecular functions in nociceptive, inflammatory and rheumatic pain pathways, and the therapeutic options they might offer.
对周围有害刺激产生的伤害性疼痛以及组织损伤引起的炎症性疼痛，起到一种警示作用，即直到刺激减弱或组织修复，正常身体功能才能恢复。刺激会使众多受体、离子通道及其他细胞机制做出反应，并将信号传导至中枢神经系统，在那里这些信息被处理并感知为疼痛。在健康个体中，组织损伤会导致生理上（通常是修复性的）变化，从而导致感觉增强，且常常引发疼痛。在风湿性疾病中，关节疼痛与慢性炎症性疼痛有许多共同之处，但潜在的疾病状态通常更为复杂，且没有明显的修复功能。应对风湿性疾病的复杂疼痛仍然是一项持续的挑战。疼痛信号通路涉及许多分子成分，这些成分有可能成为药物治疗干预的靶点，但该系统的复杂性也可能意味着必须同时影响多个位点才能中断疼痛信号的传导。此外，为了在治疗上可行，止痛药物必须安全且不改变触觉感觉功能、警觉性或认知功能。在本文中，我们综述了伤害性、炎症性和风湿性疼痛通路中的分子功能以及它们可能提供的治疗选择。
