Mori Tomohisa, Kanbara Tomoe, Harumiya Masato, Iwase Yoshiyuki, Masumoto Aki, Komiya Sachiko, Nakamura Atsushi, Shibasaki Masahiro, Kanemasa Toshiyuki, Sakaguchi Gaku, Suzuki Tsutomu
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Japan.
J Pharmacol Sci. 2014;126(1):47-55. doi: 10.1254/jphs.14134fp. Epub 2014 Aug 20.
The rewarding effects of μ-receptor agonists can be suppressed under several pain conditions. We recently showed that clinically used μ-receptor agonists possess efficacies for relieving the neuropathic pain induced by chemotherapeutic drug in rats; however, it is possible that the use of μ-receptor agonists may trigger the rewarding effects even under chemotherapeutic drug-induced neuropathic pain. Nevertheless, no information is available regarding whether μ-receptor agonists produce psychological dependence under chemotherapeutic drug-induced neuropathic pain. Therefore, we examined the effects of neuropathy induced by chemotherapeutic drugs on the rewarding effects of morphine, oxycodone, and fentanyl in rats. Repeated treatment with oxaliplatin or paclitaxel produced neuropathy as measured by the von Frey test. Rewarding effects produced by antinociceptive doses of μ-receptor agonists were not suppressed under oxaliplatin- or paclitaxel-induced neuropathy. Furthermore, the morphine-induced increase in the release of dopamine from the nucleus accumbens, which is a critical step in the rewarding effects of μ-receptor agonists, was not altered in paclitaxel-treated rats. These results suggest that the rewarding effects of μ-receptor agonists can still be established under oxaliplatin- or paclitaxel-induced neuropathic pain. Therefore, patients should be carefully monitored for psychological dependence on μ-receptor agonists when they are used to control chemotherapeutic drug-induced neuropathic pain.
μ受体激动剂的奖赏效应在多种疼痛情况下可能会受到抑制。我们最近发现，临床使用的μ受体激动剂对缓解大鼠化疗药物诱导的神经性疼痛具有疗效；然而，即使在化疗药物诱导的神经性疼痛情况下，使用μ受体激动剂仍有可能引发奖赏效应。尽管如此，关于μ受体激动剂在化疗药物诱导的神经性疼痛情况下是否会产生心理依赖，目前尚无相关信息。因此，我们研究了化疗药物诱导的神经病变对大鼠吗啡、羟考酮和芬太尼奖赏效应的影响。通过von Frey试验测量，用奥沙利铂或紫杉醇反复治疗会产生神经病变。在奥沙利铂或紫杉醇诱导的神经病变情况下，μ受体激动剂的镇痛剂量所产生的奖赏效应并未受到抑制。此外，在紫杉醇治疗的大鼠中，吗啡诱导的伏隔核多巴胺释放增加（这是μ受体激动剂奖赏效应的关键步骤）并未改变。这些结果表明，在奥沙利铂或紫杉醇诱导的神经性疼痛情况下，μ受体激动剂的奖赏效应仍然可以建立。因此，当使用μ受体激动剂来控制化疗药物诱导的神经性疼痛时，应密切监测患者对其的心理依赖情况。
