Department of Neurological Surgery, Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, 511 S. Floyd Street, Louisville, KY 40292, United States.
Neurosci Lett. 2013 Dec 17;557 Pt A(0 0):60-4. doi: 10.1016/j.neulet.2013.08.018. Epub 2013 Aug 22.
Previously preclinical pain research has focused on simple behavioral endpoints to assess the efficacy of analgesics in acute and chronic pain models, primarily reflexive withdrawal from an applied mechanical or thermal stimulus. However recent research has been aimed at investigating other behavioral states in the presence of pain, including spontaneous, non-elicited pain. One approach is to investigate the reinforcing effects of analgesics in animals with experimental pain, which should serve as reinforcers by virtue of their ability to alleviate the relevant subjective states induced by pain. The gold standard for assessing drug reinforcement is generally accepted to be drug self-administration, and this review highlights the ability of drugs to serve as reinforcers in animals with experimental neuropathic pain, and the extent to which this behavior is altered in chronic pain states. Additionally, intracranial self-stimulation is an operant procedure that has been used extensively to study drug reinforcement mechanisms and the manner in which neuropathic pain alters the ability of drugs to serve as reinforcers in this paradigm will also be discussed. Drug self-administration and intracranial self-stimulation have promise as tools to investigate behavioral effects of analgesics in animals with chronic pain, particularly regarding the mechanisms through which these drugs motivate consumption in a chronic pain state.
先前的临床前疼痛研究主要集中在使用简单的行为终点来评估镇痛药在急性和慢性疼痛模型中的疗效,主要是对施加的机械或热刺激的反射性回避。然而,最近的研究旨在研究疼痛状态下的其他行为状态,包括自发性、非诱发的疼痛。一种方法是在患有实验性疼痛的动物中研究镇痛药的强化作用,这些镇痛药应该因其减轻与疼痛相关的主观状态的能力而成为强化物。评估药物强化作用的金标准通常被认为是药物自我给药,本综述强调了药物在患有实验性神经病理性疼痛的动物中作为强化物的能力,以及这种行为在慢性疼痛状态下发生的改变程度。此外,颅内自我刺激是一种操作性程序,已广泛用于研究药物强化机制,以及神经病理性疼痛改变药物在该范式中作为强化物的能力的方式也将进行讨论。药物自我给药和颅内自我刺激有望成为研究慢性疼痛动物中镇痛药行为效应的工具,特别是这些药物在慢性疼痛状态下刺激消费的机制。