IL-1 receptor antagonist improves morphine and buprenorphine efficacy in a rat neuropathic pain model

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• 作者：Dominika Pilat ; Ewelina Rojewska ; Agnieszka M. Jurga ; Anna Piotrowska ; Wioletta Makuch ; Barbara Przewlocka ; Joanna Mika ; ^{joamika@if-pan.krakow.pl" class="auth_mail" title="E-mail the corresponding author} ; ^{joasia272@onet.eu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Neuropathic pain ; IL-1alpha ; IL-1beta ; IL-1 receptor type I ; IL-1 receptor antagonist
• 刊名：European Journal of Pharmacology
• 出版年：2015
• 出版时间：5 October 2015
• 年：2015
• 卷：764
• 期：Complete
• 页码：240-248
• 全文大小：1686 K

文摘

An interesting research and therapeutic problem is the reduced beneficial efficacy of opioids in the treatment of neuropathic pain. The present study sought to investigate the potential role of IL-1 family members in this phenomenon. We studied the time course of changes in IL-1alpha, IL-1beta, IL-1 receptor type I and IL-1 receptor antagonist mRNA and protein levels experienced by rats after chronic constriction injury (CCI) of the sciatic nerve using qRT-PCR and Western blot analysis. In CCI-exposed rats, spinal levels of IL-1alpha mRNA were slightly downregulated on the 7th day, and protein levels were not changed on the 7th and 14th days. Levels of IL-1 receptor antagonist and IL-1 receptor type I were slightly upregulated in the ipsilateral part of the spinal cord on the 7th and 14th days; however, protein levels were not changed at those time points. Interestingly, we observed that IL-1beta mRNA and protein levels were strongly elevated in the ipsilateral part of the dorsal spinal cord on the 7th and 14th days following CCI. Moreover, in rats exposed to a single intrathecal administration of an IL-1 receptor antagonist (100 ng i.t.) on the 7th and 14th day following CCI, symptoms of neuropathic pain were attenuated, and the analgesic effects of morphine (2.5 µg i.t.) and buprenorphine (2.5 µg i.t.) were enhanced. In summary, restoration of the analgesic activity of morphine and buprenorphine by blockade of IL-1 signaling suggests that increased IL-1beta responses may account for the decreased analgesic efficacy of opioids observed in the treatment of neuropathy.