Tsai Y C, Chang P J, Jou I M
Department of Anesthesiology, Medical College and Hospital, National Cheng Kung University, Tainan, Taiwan.
Anesth Analg. 2001 Jun;92(6):1547-51. doi: 10.1097/00000539-200106000-00040.
We sought to determine the possible neural conduction blockade of tramadol and whether there is evidence of localized neural toxicity with spinal somatosensory evoked potential (SSEP) measurements. Male Wistar rats were used. SSEP, elicited by supramaximally stimulating the hind paw and recorded from the thoracolumbar and the first and second lumbar interspinous ligaments, was monitored. SSEPs were obtained before drug application as the pretreatment baseline and measured every 15 min after treatment for 2 h and at 60-min intervals thereafter until SSEP returned to baseline or for another 4 h. Two small strips of Gelfoam (0.6 x 1.0 cm(2)) soaked with the drug were placed under and over the left sciatic nerve for a 30-min period. Gelfoam was prepared with tramadol hydrochloride (Tramal; the US trade name is Ultram) 5, 2.5, and 1.25 mg, diluted if needed with saline to a total volume of 100 microL (5%, 2.5%, and 1.25%, respectively). The control data were obtained from the right side limb with normal saline by following the same method. Spinal SSEPs were measured after 48 h to detect the late neural damage. The results showed that direct tramadol application on sciatic nerves dose-dependently reduced both the amplitude and conduction velocity of SSEPs when compared with the pretreatment baseline. All SSEPs returned to pretreatment baseline, and no significant changes of SSEP between bilateral limbs were noted at the 48-h measurements. No evidence of irreversible conduction blockade indicative of local neural toxicity was seen. Pretreatment with naloxone 1 mg/kg failed to block the changes of SSEP produced by 2.5% tramadol 100 microL. We conclude that tramadol exerts a local anesthetic-type effect on peripheral nerves.
我们试图确定曲马多可能的神经传导阻滞作用，以及通过脊髓体感诱发电位（SSEP）测量是否有局部神经毒性的证据。使用雄性Wistar大鼠。通过对后爪进行超强刺激并从胸腰段以及第一和第二腰椎棘间韧带记录SSEP进行监测。在给药前获取SSEP作为预处理基线，并在治疗后每15分钟测量一次，持续2小时，此后每隔60分钟测量一次，直至SSEP恢复到基线或持续另外4小时。将两条浸有药物的明胶海绵小条（0.6×1.0 cm²）置于左侧坐骨神经下方和上方30分钟。明胶海绵分别用5mg、2.5mg和1.25mg盐酸曲马多（曲马朵；美国商品名为奥施康定）制备，如有需要用生理盐水稀释至总体积100μL（分别为5%、2.5%和1.25%）。通过相同方法用生理盐水从右侧肢体获取对照数据。48小时后测量脊髓SSEP以检测晚期神经损伤。结果表明，与预处理基线相比，直接将曲马多应用于坐骨神经可剂量依赖性地降低SSEP的波幅和传导速度。所有SSEP均恢复到预处理基线，并且在48小时测量时双侧肢体的SSEP未发现显著变化。未观察到表明局部神经毒性的不可逆传导阻滞的证据。1mg/kg纳洛酮预处理未能阻断100μL 2.5%曲马多引起的SSEP变化。我们得出结论，曲马多对周围神经具有局部麻醉样作用。
