The effect of dexmedetomidine on expression of neuronal nitric oxide synthase in spinal dorsal cord in a rat model with chronic neuropathic pain

Abstract Background Neuropathic pain typically refers to the pain caused by somatosensory system injury or diseases, which is usually characterized by ambulatory pain, allodynia, and hyperalgesia. Nitric oxide produced by neuronal nitric oxide synthase (nNOS) in the spinal dorsal cord might serve a predominant role in regulating the algesia of neuropathic pain. The high efficacy and safety, as well as the plausible ability in providing comfort, entitle dexmedetomidine (DEX) to an effective anesthetic adjuvant. The aim of this study was to investigate the effect of DEX on the expression of nNOS in spinal dorsal cord in a rat model with chronic neuropathic pain. Methods Male Sprague Dawley (SD) rats were randomly assigned into three groups: sham operation group (sham), (of the sciatic nerve) operation (CCI) group, and dexmedetomidine (DEX) group. Chronic neuropathic pain models in the CCI and DEX groups were established by sciatic nerve ligation. The thermal withdrawal latency (TWL) was measured on day 1 before operation and on day 1, 3, 7 and 14 after operation. Six animals were sacrificed after TWL measurement on day 7, and 14 days after operation, in each group, the L4–6 segment of the spinal cords was extracted for determination of nNOS expression by immunohistochemistry. Results Compared with the sham group, the TWL threshold was significantly decreased and the expression of nNOS was up-regulated after operation in the CCI and DEX groups. Compared with the CCI grou[, the TWL threshold was significantly increased and the expression of nNOS was significantly down-regulated on day 7 and 14 days after operation in the DEX group. Conclusion Down-regulated nNOS in the spinal dorsal cord is involved in the attenuation of neuropathic pain by DEX.

摘要 背景 神经性疼痛通常指由躯体感觉系统损伤或疾病引起的疼痛，其特征通常表现为行走疼痛、痛觉过敏和痛觉超敏。脊髓背侧索中神经元型一氧化氮合酶（nNOS）产生的氧化氮可能在调节神经性疼痛的痛觉中发挥主导作用。由于其高疗效、安全性以及提供舒适度的可能性，右美托咪定（DEX）被认定为一种有效的麻醉辅助药物。本研究旨在探讨DEX对慢性神经性疼痛大鼠模型脊髓背侧索中nNOS表达的影响。方法 将雄性Sprague Dawley（SD）大鼠随机分为三组：假手术组（假）、坐骨神经手术（CCI）组和右美托咪定（DEX）组。通过坐骨神经结扎在CCI和DEX组建立慢性神经性疼痛模型。在手术前第1天和手术后的第1、3、7和14天测量热抽搐潜伏期（TWL）。在第7天和手术后第14天，每组各处死6只动物，提取脊髓L4–6节段以通过免疫组织化学方法测定nNOS表达。结果 与假手术组相比，CCI和DEX组手术后的TWL阈值显著降低，nNOS表达上调。与CCI组相比，DEX组在第7天和手术后的第14天，TWL阈值显著增加，nNOS表达显著下调。结论 脊髓背侧索中nNOS的下调参与DEX减轻神经性疼痛的过程。