Zhang Wei, Liu Yue, Hou Bailing, Gu Xiaoping, Ma Zhengliang
Department of Anesthesiology, Drum Tower Hospital of Clinic Department of Nanjing Medical University Nanjing 210008, Jiangsu, People's Republic of China.
Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University Nanjing 210008, Jiangsu Province, China.
Int J Clin Exp Med. 2015 Feb 15;8(2):1871-9. eCollection 2015.
The activation of alpha-7 nicotinic acetylcholine receptors (α7-nAchRs) are currently being considered as novel therapeutic approaches for managing hyperalgesia in inflammation and chronic neuropathic pain, but the role of a7-nAChRs on opioids induced hyperalgesia remain unknown. The present study investigated the effects of α7-nAChRs selective agonists PHA-543613 and type II positive allosteric modulators (PAMs) PNU-120596 in remifentanil induced postoperative hyperalgesia. As the results shown, intrathecal treatment with both α7-nAChRs agonists and type II PAMs could attenuate remifentanil induced hyperalgesia by increasing paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL). Furthermore, we also investigated the protein level of proinflammatory cytokines and phosphorylation N-methyl-d-aspartate receptor 2B subunit (p-NR2B) in the spinal cord. Our data indicated that activation of α7-nAchRs decreased the proinflammatory cytokines (TNF-α, IL-6) and p-NR2B protein level in the spinal cord. The depression of the increased levels of proinflammatory cytokines and p-NR2B after remifentanil treatment may contribute to the anti-hyperalgesia effects of PHA-543613and PNU-120596 via α7-nAChRs. Therefore, our findings demonstrated that α7-nAChRs may be potential candidates for treating opioids induced hyperalgesia.
α7烟碱型乙酰胆碱受体（α7-nAchRs）的激活目前被视为治疗炎症性痛觉过敏和慢性神经性疼痛的新型治疗方法，但α7-nAChRs在阿片类药物诱导的痛觉过敏中的作用尚不清楚。本研究调查了α7-nAChRs选择性激动剂PHA-543613和II型正变构调节剂（PAMs）PNU-120596在瑞芬太尼诱导的术后痛觉过敏中的作用。结果显示，鞘内注射α7-nAChRs激动剂和II型PAMs均可通过提高爪部撤离机械阈值（PWMT）和爪部撤离热潜伏期（PWTL）来减轻瑞芬太尼诱导的痛觉过敏。此外，我们还研究了脊髓中促炎细胞因子和磷酸化N-甲基-D-天冬氨酸受体2B亚基（p-NR2B）的蛋白水平。我们的数据表明，激活α7-nAchRs可降低脊髓中促炎细胞因子（TNF-α、IL-6）和p-NR2B蛋白水平。瑞芬太尼治疗后促炎细胞因子和p-NR2B水平升高的降低可能是PHA-543613和PNU-120596通过α7-nAChRs产生抗痛觉过敏作用的原因。因此，我们的研究结果表明α7-nAChRs可能是治疗阿片类药物诱导的痛觉过敏的潜在候选药物。
