Effects of local tramadol administration on peripheral glutamate-induced nociceptive behaviour in mice

Purpose The use of peripheral tramadol to block pain has been advocated. However, since its actions in the periphery have not been elucidated fully, we tested the hypothesis that peripheral tramadol blocks peripheral glutamate-induced nociceptive behaviour in mice. Methods First, we compared the duration of paw licking after intraplantar (ipl.) glutamate administration, with and without tramadol, using a randomized blinded controlled design. Next, we established the half maximal effective concentrations (EC 50s ) for local tramadol and reference compound lidocaine in the hot water tail-flick latency test and the glutamate-induced paw allodynia assay. Results Tramadol reduced glutamate-induced paw licking from 33 ± 12 sec to 4 ± 4 sec (mean ± SD; t test, P < 0.05; n = 6 per group). The tramadol and lidocaine EC 50 nerve conduction blocks in the tail did not differ significantly (84 ± 24 mM vs 69 ± 5 mM, respectively). Although tramadol reduced glutamate-induced allodynia (EC 50 , 46 ± 13 mM), lidocaine was more potent (EC 50 , 13 ± 5 mM; Dixon’s up-and-down method; P < 0.05). Tramadol was 2.5 times as effective at blocking nerve conduction in the tail compared with allodynia in the paw. Conclusions Local tramadol administration blocked nociceptive behaviour in mice induced by peripheral glutamate. Compared with lidocaine, the relative potency of tramadol was lower for blocking glutamate-induced allodynia than for sensory nerve conduction blockade, suggesting the activation of a pronociceptive receptor system in the periphery.