Liu Baowen, Liu Yi, Li Ningbo, Zhang Jin, Zhang Xianwei
Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China,
J Pain Res. 2018 Oct 30;11:2663-2674. doi: 10.2147/JPR.S180396. eCollection 2018.
Oxycodone, which is one of the most commonly used opiates in postoperative pain management, has a different affinity for μ-opioid receptors (MOR), κ-opioid receptors (KOR), and δ-opioid receptors (DOR). Accumulating research has suggested that neurotrophins (NTs) are involved in opioid analgesia. In the current exploratory study, we aimed to investigate the underlying mechanisms of the analgesic effects of oxycodone on post-surgery pain in rats and to determine whether neurotrophic factors and receptors were involved in these effects.
Mechanical and thermal sensitivity tests were used to evaluate the validity of the postoperative pain rat model and to determine the analgesic effect of oxycodone. Quantitative PCR and Western blot analysis were used to detect the changes in the expression of three types of opioid receptors and NTs and their high-affinity receptors in the spinal cord after surgery and oxycodone administration.
Oxycodone showed an analgesic effect on plantar incision (PI)-induced hyperalgesia, especially thermal hyperalgesia. We detected an obvious increase in MOR expression levels but insignificant changes in KOR and DOR levels in the spinal cord after PI. Moreover, we found that oxycodone was able to reverse the increased expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor (TrK) A, and TrkB and the decreased expression of NT-3 and TrkC, after PI. Pretreatment with oxycodone also altered the expression of these mediators.
Based on the results, possible underlying mechanisms for the antinociceptive properties of oxycodone in acute postoperative pain include the activation of MOR downstream signaling and the regulation of NTs and receptor expression through attenuation of glial activation and fortification of antinociceptive mediators in the spinal cord. This study may provide new insights into the molecular mechanisms underlying the analgesic action of oxycodone.
羟考酮是术后疼痛管理中最常用的阿片类药物之一，对μ-阿片受体（MOR）、κ-阿片受体（KOR）和δ-阿片受体（DOR）具有不同的亲和力。越来越多的研究表明，神经营养因子（NTs）参与阿片类镇痛。在当前的探索性研究中，我们旨在研究羟考酮对大鼠术后疼痛的镇痛作用的潜在机制，并确定神经营养因子及其受体是否参与这些作用。
采用机械和热敏感性测试来评估术后疼痛大鼠模型的有效性，并确定羟考酮的镇痛效果。采用定量PCR和蛋白质印迹分析来检测手术和给予羟考酮后脊髓中三种阿片受体、NTs及其高亲和力受体表达的变化。
羟考酮对足底切口（PI）诱导的痛觉过敏，尤其是热痛觉过敏有镇痛作用。我们检测到PI后脊髓中MOR表达水平明显升高，但KOR和DOR水平变化不显著。此外，我们发现羟考酮能够逆转PI后神经生长因子（NGF）、脑源性神经营养因子（BDNF）、酪氨酸激酶受体（TrK）A和TrkB表达的增加以及NT-3和TrkC表达的降低。羟考酮预处理也改变了这些介质的表达。
基于这些结果，羟考酮在急性术后疼痛中抗伤害感受特性的可能潜在机制包括MOR下游信号的激活以及通过减弱胶质细胞激活和增强脊髓中抗伤害感受介质来调节NTs和受体表达。本研究可能为羟考酮镇痛作用的分子机制提供新的见解。
