Uhelski Megan L, Fuchs Perry N
University of Texas at Arlington, Department of Psychology, Box 19528, Arlington, TX 76019, United States.
Physiol Behav. 2009 Sep 7;98(3):263-7. doi: 10.1016/j.physbeh.2009.05.019. Epub 2009 Jun 6.
The non-specific opioid antagonist naltrexone has traditionally been used as treatment for opioid overdose, as well as in research settings as an antagonist to examine opioid and non-opioid mediated analgesia. However, the mechanisms by which this drug operates are not well understood, and its exact effects on sensory and affective pain processes remain uncertain. Various studies have demonstrated that naltrexone behaves in a paradoxical manner, leading to analgesia, no discernable changes, or an increase in pain, depending on the circumstances of the study. This imprecise spectrum of effects leads to difficulty in interpreting results in studies where naltrexone was utilized as an antagonist. Therefore, the purpose of this experiment was to further examine whether naltrexone elicits dose-dependent effects in behavioral tests designed to quantify the sensory and affective components of pain. Naltrexone was not expected to have an effect on carrageenan-induced inflammatory pain in sensory pain measures, but a dose-dependent increase was predicted in behavior related to the affective component of pain. Eighty-eight male Sprague-Dawley rats were used to test these hypotheses by measuring Mechanical Paw Withdrawal Thresholds before and after naltrexone injection and by assessing performance in the Place Escape Avoidance Paradigm test, a novel paradigm to test pain affect, in which naltrexone had not been utilized. The results demonstrated that naltrexone failed to increase place/escape avoidance behavior as anticipated, but rather produced a slight, but non-significant, decrease in escape avoidance behavior. Further research is needed to elucidate the differential effects of naltrexone on various aspects of pain-related behavior.
非特异性阿片类拮抗剂纳曲酮传统上用于治疗阿片类药物过量，以及在研究环境中作为拮抗剂来研究阿片类和非阿片类介导的镇痛作用。然而，这种药物的作用机制尚未完全了解，其对感觉性和情感性疼痛过程的确切影响仍不确定。各种研究表明，纳曲酮的表现自相矛盾，根据研究情况，会导致镇痛、无明显变化或疼痛加剧。这种不精确的效应范围导致在将纳曲酮用作拮抗剂的研究中难以解释结果。因此，本实验的目的是进一步研究纳曲酮在旨在量化疼痛的感觉和情感成分的行为测试中是否产生剂量依赖性效应。预计纳曲酮在感觉性疼痛测量中对角叉菜胶诱导的炎性疼痛没有影响，但预计在与疼痛情感成分相关的行为中会出现剂量依赖性增加。88只雄性斯普拉-道利大鼠通过测量纳曲酮注射前后的机械性爪退缩阈值，并通过评估在位置逃避回避范式测试（一种未使用过纳曲酮的测试疼痛情感的新范式）中的表现来检验这些假设。结果表明，纳曲酮未能如预期那样增加位置/逃避回避行为，反而使逃避回避行为略有下降，但不显著。需要进一步研究以阐明纳曲酮对疼痛相关行为各个方面的不同影响。
