Asaoka Yuta, Kato Takahiro, Ide Soichiro, Amano Taiju, Minami Masabumi
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan; Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
Neurosci Lett. 2018 Mar 6;668:133-137. doi: 10.1016/j.neulet.2018.01.029. Epub 2018 Jan 31.
The present study aimed to examine the rewarding effects of pain relief during the early and late stages of neuropathic pain using a conditioned place preference (CPP) test. Animal models of neuropathic pain were prepared by spinal nerve ligation in male Sprague-Dawley rats. Intraperitoneal and intrathecal injections of pregabalin (300 mg/kg and 100 μg/10 μL, respectively) suppressed allodynia in the von Frey test both 2 weeks (early stage) and 4 weeks (late stage) after nerve injury. Intraperitoneal and intrathecal injections of pregabalin induced CPP during the early stage of neuropathic pain, suggesting that the CPP test serves as an objective and quantifiable behavioral assay to assess the emotional aspect of pain relief. In contrast with the early stage of neuropathic pain, intraperitoneal or intrathecal injection of pregabalin did not induce CPP during the late stage of neuropathic pain. The extinguishment of the rewarding effects of pregabalin during the late stage of neuropathic pain is likely due to dysfunction of the mesolimbic reward system, although the possibility that neuronal mechanisms other than dysfunction of the mesolimbic reward system are involved in the extinguishment of pregabalin-induced CPP cannot be excluded. We previously reported that not only the dopamine release in the nucleus accumbens induced by intrathecal pregabalin injection but also that induced by sucrose intake were extinguished during the late stage of neuropathic pain. These findings, combined with the results of this study, suggest that pain chronification leads to dysfunction of the mesolimbic reward system.
本研究旨在使用条件性位置偏爱（CPP）试验，检测神经性疼痛早期和晚期疼痛缓解的奖赏效应。通过对雄性Sprague-Dawley大鼠进行脊神经结扎制备神经性疼痛动物模型。腹腔注射和鞘内注射普瑞巴林（分别为300mg/kg和100μg/10μL）在神经损伤后2周（早期）和4周（晚期）均抑制了von Frey试验中的痛觉过敏。腹腔注射和鞘内注射普瑞巴林在神经性疼痛早期诱导了CPP，这表明CPP试验可作为一种客观且可量化的行为测定方法，用于评估疼痛缓解的情感方面。与神经性疼痛早期不同，腹腔注射或鞘内注射普瑞巴林在神经性疼痛晚期未诱导出CPP。神经性疼痛晚期普瑞巴林奖赏效应的消退可能是由于中脑边缘奖赏系统功能障碍，尽管不能排除除中脑边缘奖赏系统功能障碍之外的神经元机制参与普瑞巴林诱导的CPP消退的可能性。我们之前报道过，鞘内注射普瑞巴林诱导的伏隔核多巴胺释放以及蔗糖摄入诱导的多巴胺释放，在神经性疼痛晚期均会消退。这些发现与本研究结果相结合，表明疼痛慢性化会导致中脑边缘奖赏系统功能障碍。
