Discipline of Physiology, School of Medical Sciences, University of Adelaide, Australia.
Brain Behav Immun. 2013 May;30:3-11. doi: 10.1016/j.bbi.2013.03.002. Epub 2013 Mar 14.
Despite the wealth of evidence in animals that immune activation has a key role in the development and maintenance of chronic pain, evidence to support this in humans is scant. We have sought such evidence by examining the effect of a subtle immunological stimulus, low dose intravenous endotoxin, on the allodynia, hyperalgesia, flare and pain produced by intradermal capsaicin in healthy volunteers. Here we provide evidence of immune priming of this neuropathic-like pain response in humans. Specifically, in 12 healthy volunteers, activation of Toll-Like Receptor 4 by endotoxin (0.4ng/kg IV) caused significant 5.1-fold increase in the 90-min integral of areas of capsaicin-induced allodynia (95% CI 1.3-9.1), 2.2-fold increase in flare (95% CI 1.9-2.6) and 1.8-fold increase in hyperalgesia (95% CI 1.1-2.5) following 50μg intradermal capsaicin injected into the forearm 3.5h after endotoxin. These data demonstrate clinically a significant role for the neuroimmune pain connection in modifying pain, thus providing evidence that immune priming may produce pain enhancement in humans and hence offer a novel range of pharmacological targets for anti-allodynics and/or analgesics. Additionally, the simplicity of the model makes it suitable as a test-bed for novel immune-targeted pain therapeutics.
尽管有大量证据表明免疫激活在慢性疼痛的发展和维持中起着关键作用，但在人类中支持这一观点的证据很少。我们通过检查一种微妙的免疫刺激物——低剂量静脉内内毒素对健康志愿者皮内辣椒素引起的触痛、痛觉过敏、 flare 和疼痛的影响来寻找这种证据。在这里，我们提供了人类这种神经病理性疼痛反应免疫启动的证据。具体来说，在 12 名健康志愿者中，内毒素（0.4ng/kg IV）激活 Toll 样受体 4 导致皮内辣椒素引起的触痛（95%置信区间 1.3-9.1）的 90 分钟积分显著增加 5.1 倍， flare（95%置信区间 1.9-2.6）增加 2.2 倍，痛觉过敏（95%置信区间 1.1-2.5）增加 1.8 倍，内毒素注射后 3.5 小时在前臂皮内注射 50μg 辣椒素后。这些数据在临床上证明了神经免疫疼痛连接在调节疼痛方面的重要作用，从而提供了证据表明免疫启动可能会在人类中产生疼痛增强，从而为抗触痛和/或镇痛的新型免疫靶向治疗提供了新的靶点。此外，该模型的简单性使其适合作为新型免疫靶向疼痛治疗的测试平台。
