Tsai Y C, Sung Y H, Chang P J, Kang F C, Chu K S
Department of Anesthesiology, Medical College & Hospital, National Cheng Kung University, Tainan, Taiwan.
Fundam Clin Pharmacol. 2000 Jul-Aug;14(4):335-40. doi: 10.1111/j.1472-8206.2000.tb00414.x.
The present study was designed to test whether tramadol is effective in the control of neuropathic pain in rats. Chronic constriction injury (CCI) of the sciatic nerve was induced over the left hind limb in male Sprague-Dawley rats. Identical surgery was performed on the opposite side except that the sciatic nerve was not ligated (sham surgery). Paw withdrawal latency (PWL) to heat was tested for each hind paw 1 day before surgery and on the 4th day after surgery to ensure the development of thermal hyperalgesia. In the acute treatment groups, saline or tramadol was administered subcutaneously at doses of 10, 20 or 30 mg/kg, and PWLs were measured 30, 60, 90, 120, 150 and 180 min after treatment. In the semi-chronic treatment groups, continuous systemic administration of tramadol 40 mg/kg/day or saline for 7 days was provided at a uniform rate via osmotic mini pumps. Tramadol reversed PWL in a dose-dependent manner in the acute treatment groups. PWLs were significantly reversed at 2 days after tramadol infusion, and this effect was sustained throughout the remainder of the treatment period in comparison with the saline group. Tramadol also resulted in a decreased sensitivity to thermal stimulus on the sham limb both in acute and semi-chronic administration. We conclude that both acute and semi-chronic tramadol treatment relieves thermal hyperalgesia effectively in rats with CCI of the sciatic nerve. This indicates that tramadol shows promise as a potential treatment for relief of neuropathic pain in humans.
本研究旨在测试曲马多是否能有效控制大鼠的神经性疼痛。在雄性Sprague-Dawley大鼠的左后肢诱导坐骨神经慢性压迫损伤(CCI)。在对侧进行相同的手术,但坐骨神经不结扎(假手术)。在手术前1天和手术后第4天测试每只后爪对热的缩爪潜伏期(PWL),以确保热痛觉过敏的发展。在急性治疗组中,以10、20或30mg/kg的剂量皮下注射生理盐水或曲马多,并在治疗后30、60、90、120、150和180分钟测量PWL。在半慢性治疗组中,通过渗透微型泵以均匀速率连续7天全身给予40mg/kg/天的曲马多或生理盐水。在急性治疗组中,曲马多以剂量依赖性方式逆转PWL。在曲马多输注后2天,PWL显著逆转,与生理盐水组相比,这种效应在治疗期的其余时间持续存在。在急性和半慢性给药中,曲马多还导致假手术肢体对热刺激的敏感性降低。我们得出结论,急性和半慢性曲马多治疗均能有效缓解坐骨神经CCI大鼠的热痛觉过敏。这表明曲马多有望成为缓解人类神经性疼痛的潜在治疗方法。