Activation of Peripheral Excitatory Amino Acid Receptors Decreases the Duration of Local Anesthesia

Abstract

Background Postsurgical wound infiltration with the -methyl-d-aspartate receptor antagonist ketamine and bupivacaine can significantly prolong the duration of local anesthesia. One possible mechanism for this effect is that increased glutamate concentrations, caused by tissue damage, sensitize nociceptive primary afferent fibers through activation of peripheral excitatory amino acid receptors. Methods The effect of intramuscular injection of hyper-tonic glutamate (1,000 mm), dextrose (1,400 mm), glutamate (1,000 mm) with the broad spectrum excitatory amino acid receptor antagonist kynurenate (100 mm), or isotonic saline (155 mm) on the duration of masseter muscle afferent fiber blockade after lidocaine (37 mm [1%], 10 microl) infiltration, on muscle edema formation and on muscle blood flow was examined. Results Injection of either glutamate or dextrose significantly shortened the duration of lidocaine blocks compared with isotonic saline; however, block duration was significantly shorter after glutamate than after dextrose. Injection of glutamate, but not isotonic saline, dextrose, or glutamate with kynurenate, significantly decreased the mechanical threshold of muscle afferent fibers. Injection of glutamate, dextrose, or glutamate with kynurenate produced equivalent large, long-lasting (> 60 min) edemas with high initial peak extracellular water content. Peak extracellular water decreased more rapidly when kynurenate was coinjected with glutamate. Both glutamate and dextrose significantly increased muscle blood flow for 30 min after injection. Glutamate-induced increases in blood flow were attenuated by kynurenate. Conclusions These results suggest that shortened lidocaine block durations observed after glutamate injection into the masseter muscle result from sensitization of afferent fibers as well as increases of peak extracellular water content and blood flow in masseter muscle. These effects of glutamate are mediated in part through activation of peripheral excitatory amino acid receptors.