Tramadol, but not its major metabolite (mono‐O‐demethyl tramadol) depresses compound action potentials in frog sciatic nerves

Abstract

Background and purpose: Although tramadol is known to exhibit a local anaesthetic effect, how tramadol exerts this effect is not understood fully. Experimental approach: The effects of tramadol and its metabolite mono-O-demethyl-tramadol (M1) on compound action potentials (CAPs) were examined by applying the air-gap method to frog sciatic nerves, and the results were compared with those of other local anaesthetics, lidocaine and ropivacaine. Key results: Tramadol reduced the peak amplitude of the CAP in a dose-dependent manner (IC 50 ¼ 2.3 mM). On the other hand, M1 (1-2 mM), which exhibits a higher affinity for m-opioid receptors than tramadol, did not affect CAPs. These effects of tramadol were resistant to the non-selective opioid receptor antagonist naloxone and the m-opioid receptor agonist, DAMGO, did not affect CAPs. This tramadol action was not affected by a combination of the noradrenaline uptake inhibitor, desipramine, and the 5-hydroxytryptamine uptake inhibitor, fluoxetine. Lidocaine and ropivacaine also concentrationdependently reduced CAP peak amplitudes with IC 50 values of 0.74 and 0.34 mM, respectively. Conclusions and implications: These results indicate that tramadol reduces the peak amplitude of CAP in peripheral nerve fibres with a potency which is less than those of lidocaine and ropivacaine, whereas M1 has much less effect on CAPs. This action of tramadol was not produced by activation of m-opioid receptors nor by inhibition of noradrenaline and 5-hydroxytryptamine uptake. It is suggested that the methyl group present in tramadol but not in M1 may play an important role in producing nerve conduction block.

The Effect of Tramadol on the Rat Sciatic Nerve Conduction: A Numerical Analysis and Conduction Velocity Distribution Study

“…1), which is consistent with the literatures. 1,23,24) There is a decrement in peak amplitude of CAP and prolonged latency in both Dt latency and Dt peak in a dose-dependent manner.…”

“…2,22) Such an inhibition on CAP by a non-narcotic opioid tramadol, (1RS; 2RS)-2-[(dimethylamino) methyl]-1-(3-methoxyphenyl)-cylohexanol hydrochloride was also reported. 1,23) With this study, we have intended to investigate how the conduction parameters of rat nerve trunks are aŠected when the nerve is treated with diŠerent concentrations of tramadol.…”

“…1) Tested doses of tramadol were applied to perfusion medium cumulatively and sciatic nerves were exposed to each dose for 20 minutes which is the time required for maximal decrease in CAP amplitude. 1) Square-shaped supramaximal pulses of 0.2 ms duration at a frequency of 1 Hz were applied from the proximal end of the nerve trunk through a stimulus isolation unit (Model SIU5, Grass Instruments) connected to a stimulator (Model S88K, Grass Instruments) and distal end of the nerve was inserted in suction electrode for recording in order to guarantee recording from the same number of bers activated at any point along the nerve.…”

“…Opioids are also postulated to exhibit a local anaesthetic eŠect in the peripheral nervous system. 1,2) Compound action potentials (CAPs) recorded from nerve trunk contains information concerning the number of activeˆbers and the propagation velocities of their action potentials. For the functional investigation of nerves in situ, the CAP has widespread application in basic research and in clinics; such as to determine the functional state of that particular nerve, diagnose any nervous disease, observe the nerve's growth, or deduce the conduction velocity distribution.…”

Protein Gelation around Axons Inhibits Action Potential Propagation in Nerve Fibers

“…Throughout the dissection, amphibian Ringer's solution (111 mM NaCl, 1.9 mM KCl, 1.06 mM CaCl 2 , 1.0 mM Trizma base, 5.55 mM glucose, pH 7.6) was used to moisten the dissection area and nerve. The sciatic nerves were then isolated following standard dissection procedures and placed into a dish of Ringer's solution [16].…”