期刊
PAIN
卷 161, 期 12, 页码 2798-2804出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/j.pain.0000000000001968
关键词
Ongoing pain; Inflammatory pain; Mu-opioid receptor; Conditioned place preference; Analgesia
资金
- Bundesministerium fur Bildung und Forschung [VIP 0272/03V0364]
- Deutsche Forschungsgemeinschaft [STE 477/19-1]
- Charite 3R\ Replace-Reduce-Refine
Currently, opioids targeting mu-opioid receptors are the most potent drugs for acute and cancer pain. However, opioids produce adverse side effects such as constipation, respiratory depression, or addiction potential. We recently developed (6)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide (NFEPP), a compound that does not evoke central or intestinal side effects due to its selective activation of mu-opioid receptors at low pH in peripheral injured tissues. Although we demonstrated that NFEPP effectively abolishes injury-induced pain, hyperalgesia, and allodynia in rodents, the efficacy of NFEPP in nonevoked ongoing pain remains to be established. Here, we examined reward, locomotor activity, and defecation in rats with complete Freund's adjuvantinduced paw inflammation to compare fentanyl's and NFEPP's potentials to induce side effects and to inhibit spontaneous pain. We demonstrate that low, but not higher, doses of NFEPP produce conditioned place preference but not constipation or motor disturbance, in contrast to fentanyl. Using a peripherally restricted antagonist, we provide evidence that NFEPP-induced place preference is mediated by peripheral opioid receptors. Our results indicate that a low dose of NFEPP produces reward by abolishing spontaneous inflammatory pain.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据