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

Abstract

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. RésuméObjectif L'utilisation de tramadol pe´riphe´rique a e´teṕ ropose´e pour bloquer la douleur. Cependant, comme nous ne connaissons pas pleinement ses actions sur les nerfs pe´riphe´riques, nous avons e´mis l'hypothe`se que le tramadol pe´riphe´rique bloquait les comportements nociceptifs provoque´s par le glutamate pe´riphe´rique chez la souris. Méthode Nous avons d'abord compare´la dure´e du le´chage de la patte apre`s une administration intraplantaire (ipl.) de glutamate, avec ou sans tramadol, en utilisant une me´thode contrôle´e randomise´e en aveugle. Ensuite, nous avons de´termine´les concentrations efficaces moyennes (CE 50 ) pour le tramadol administre´localement et un compose´de lidocaı¨ne comme re´fe´rence a`l'aide du test de latence du retrait de la queue et du test d'allodynie de la patte provoque´e par le glutamate. Résultats Le tramadol a re´duit le le´chage de patte provoque´par le glutamate de 33 ± 12 sec a`4 ± 4 sec (moyenne ± ET; test t, P \ 0,05; n = 6 par groupe). Les CE 50 pour le bloc de conduction nerveuse re´alise´avec le

Comparison of lidocaine, lidocaine-morphine, lidocaine-tramadol or bupivacaine for neural blockade of the brachial plexus in fat-tailed lambs

“…; Wang et al. ). Tramadol may also induce analgesia via a systemic mechanism after vascular absorption.…”

“…Recent clinical and laboratory studies have demonstrated that tramadol displays a peripheral local anaesthetic effect (Antonucci 2001;Tsai et al 2001). There are a number of possible peripheral mechanisms of action for tramadol, including a l-opioid agonist effect, agonism at peripheral a 2 -receptors, activation of serotonin receptors on peripheral nerves, local anaesthetic properties possibly by blocking potassium channels and, finally, glutamate N-methyl-D-aspartate (NMDA) receptor antagonism (Tsai et al 2001;Wang et al 2010). Tramadol may also induce analgesia via a systemic mechanism after vascular absorption.…”

Comparison of epidural tramadol-ropivacaine and fentanyl-ropivacaine for labor analgesia: A prospective randomized study

“…The analgesia effects of tramadol are mainly attributed to its dual mechanism of action as previously described (4). Added to this, its local anesthetic action may be another possible mechanism responsible for its analgesia effects (10). Importantly, it provided effective analgesia without significant respiratory, hemodynamic, or neurovirulent side-effects (5).…”

Spinal and peripheral adenosine A1 receptors contribute to antinociception by tramadol in the formalin test in mice

“…In addition to well-recognized systemic actions of tramadol, several preclinical studies report antinociception following spinal (Jesse and Nogueira, 2010;Li et al, 2012) and local peripheral administration (Pozos-Guillén et al, 2006;Mert et al, 2007;Wang et al, 2010). Furthermore, tramadol is now recognized to interact with additional cellular targets, such as Na + channels (Haeseler et al, 2006), N-methyl-D-aspartate (NMDA) receptors (Hara et al, 2005), and transient receptor potential vanilloid-1 (TRPV1) receptors (Marincsák et al, 2008), and such actions also may contribute to antinociception, particularly when tramadol is given locally and higher local tissue concentrations occur.…”