Direct Tramadol Application on Sciatic Nerve Inhibits Spinal Somatosensory Evoked Potentials in Rats

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 × 1.0 cm2) 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 μL (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 μL. We conclude that tramadol exerts a local anesthetic–type effect on peripheral nerves.