Department of Anesthesiology, National Cancer Center, Goyangsi, Republic of Korea.
Neurotoxicology. 2011 Dec;32(6):864-70. doi: 10.1016/j.neuro.2011.05.011. Epub 2011 Jun 6.
Epidural injection of cyclooxygenase-2 inhibitors has been suggested as a useful therapeutic modality in pain management in animal studies and clinical settings. Direct epidural administration of parecoxib, a highly selective cyclooxygenase-2 inhibitor, may have advantages over its parenteral administration regarding required dose, side effects, and efficacy. However, no animal studies have been performed to investigate the possible neurotoxicity of epidurally injected parecoxib. Therefore, the present study was performed to assess the neurotoxicity of epidurally injected parecoxib in rats. Rats (n=45) were randomly divided into three groups: normal saline group (group N, n=15), ethanol group (group E, n=15), and parecoxib group (group P, n=15). 0.3 mL of epidural parecoxib (6 mg) and the same volume of epidural ethanol or normal saline were injected into the epidural space. Neurologic assessment was performed 3, 7 and 21 days after the injection by pinch toe testing. Histologic changes were evaluated for vacuolation of the dorsal funiculus, chromatolytic changes of the motor neurons, neuritis, and meningeal inflammation. All rats in groups N and P showed normal response to pinch-toe testing and had a normal gait at each observation point. Histological examination showed no evidence suggestive of neuronal body or axonal lesions, gliosis, or myelin sheet damage in group N or P at any time. However, all rats in group E showed sensory-motor dysfunction, behavioral change, or histopathological abnormalities. No neurotoxicity on the spinal cord or abnormalities in sensorimotor function or behavior was noted in rats that received epidural parecoxib.
硬膜外注射环氧化酶-2 抑制剂在动物研究和临床环境中已被证明是一种有效的疼痛管理治疗方法。与全身给药相比，高选择性环氧化酶-2 抑制剂帕瑞昔布的硬膜外给药在所需剂量、副作用和疗效方面可能具有优势。然而，尚未进行动物研究来调查硬膜外注射帕瑞昔布的可能神经毒性。因此，本研究旨在评估硬膜外注射帕瑞昔布对大鼠的神经毒性。大鼠（n=45）随机分为三组：生理盐水组（N 组，n=15）、乙醇组（E 组，n=15）和帕瑞昔布组（P 组，n=15）。将 0.3 mL 硬膜外帕瑞昔布（6 mg）和相同体积的硬膜外乙醇或生理盐水注入硬膜外腔。注射后 3、7 和 21 天通过夹趾测试进行神经学评估。评估背柱空泡化、运动神经元色质溶解变化、神经炎和脑膜炎症的组织学变化。N 组和 P 组的所有大鼠均对夹趾测试有正常反应，在每个观察点均有正常步态。组织学检查显示，N 组或 P 组在任何时间均未发现神经元体或轴突病变、神经胶质增生或髓鞘片损伤的证据。然而，E 组的所有大鼠均表现出感觉运动功能障碍、行为改变或组织病理学异常。接受硬膜外帕瑞昔布的大鼠未观察到脊髓神经毒性或感觉运动功能或行为异常。
