van Amerongen Guido, de Boer Matthijs W, Groeneveld Geert Jan, Hay Justin L
Centre for Human Drug Research (CHDR), Leiden, The Netherlands.
Br J Clin Pharmacol. 2016 Oct;82(4):903-22. doi: 10.1111/bcp.13018. Epub 2016 Jul 8.
Human evoked pain models can be used to determine the efficacy of new and existing analgesics and to aid in the identification of new targets. Aspects of neuropathic pain can be simulated by inducing hyperalgesia resulting from provoked sensitization. The present literature review aimed to provide insight into the sensitivity of different hyperalgesia and allodynia models of pharmacological treatment.
A literature search was performed to identify randomized, double-blind, placebo-controlled studies that included human hyperalgesia pain models and investigated the pharmacodynamic effects of different classes of drugs.
Three hyperalgesia models [ultraviolet B (UVB) irradiation, capsaicin and thermode burn] have been used extensively. Assessment of hyperalgesia/allodynia and pharmacological effect are measured using challenge tests, which generally comprise thermal (heat/cold) or mechanical stimulation (pin-prick, stroking or impact). The UVB model was sensitive to the antihyperalgesic effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids. The capsaicin model was partially sensitive to opioids. The burn model did not detect any antihyperalgesic effects when NSAIDs or local anaesthetics were administered but responded to the effects of N-methyl D-aspartate (NMDA) receptor antagonists by moderately reducing mechanical hyperalgesia.
Based on pharmacological sensitivity, the UVB model adequately reflects inflammatory pain and was sensitive to NSAIDs and opioids. Findings from the capsaicin and burn models raised questions about the translatability of these models to the treatment of neuropathic pain. There is a need for a reproducible and predictive model of neuropathic pain, either in healthy subjects or in patients.
人体诱发疼痛模型可用于确定新型和现有镇痛药的疗效,并有助于识别新的靶点。神经性疼痛的某些方面可通过诱发敏化导致的痛觉过敏来模拟。本综述旨在深入了解不同痛觉过敏和异常性疼痛模型对药物治疗的敏感性。
进行文献检索,以识别随机、双盲、安慰剂对照研究,这些研究纳入人体痛觉过敏疼痛模型并研究不同类别药物的药效学作用。
三种痛觉过敏模型[紫外线B(UVB)照射、辣椒素和热刺激烧伤]已被广泛使用。使用激发试验来评估痛觉过敏/异常性疼痛和药理作用,激发试验通常包括热(热/冷)或机械刺激(针刺、抚摸或冲击)。UVB模型对非甾体抗炎药(NSAIDs)和阿片类药物的抗痛觉过敏作用敏感。辣椒素模型对阿片类药物部分敏感。当给予NSAIDs或局部麻醉药时,烧伤模型未检测到任何抗痛觉过敏作用,但对N-甲基-D-天冬氨酸(NMDA)受体拮抗剂的作用有反应,可适度减轻机械性痛觉过敏。
基于药理敏感性而言,UVB模型能充分反映炎性疼痛,且对NSAIDs和阿片类药物敏感。辣椒素模型和烧伤模型的研究结果引发了对这些模型在神经性疼痛治疗中可转化性的质疑。无论是在健康受试者还是患者中,都需要一种可重复且具有预测性的神经性疼痛模型。