Effect of intrathecal glycine and related amino acids on the allodynia and hyperalgesic action of strychnine or bicuculline in mice

BACKGROUND The intrathecal (IT) administration of glycine or GABA(A) receptor antagonist result in a touch evoked allodynia through disinhibition in the spinal cord. Glycine is an inhibitory neurotransmitter that appears to be important in sensory processing in the spinal cord. This study was aimed to evaluate the effect of glycine-related amino acids on antagonizing the effects of IT strychnine (STR) or bicuculline (BIC) when each amino acid was administered in combination with STR or BIC. METHODS A total of 174 male ICR mice were randomized to receive an IT injection of equimolar dose of glycine, betaine, beta-alanine, or taurine in combination with STR or BIC. Agitation in response to innocuous stimulation with a von Frey filament after IT injection was assessed. The pain index in hot-plate test were observed after IT injection. The effect of IT muscimol in combination with STR or BIC were also observed. RESULTS The allodynia induced by STR was relieved by high dose of glycine or betaine. But, allodynia induced by BIC was not relieved by any amino acid. Whereas the STR-induced thermal hyperalgesia was only relieved by high dose of taurine at 120 min after IT injection, the BIC-induced one was relieved by not only high dose of taurine at 120 min but also low dose of glycine or betaine at 60 min after IT injection. The BIC-induced allodynia and thermal hyperalgesia was relieved by IT muscimol. CONCLUSIONS This study suggests that IT glycine and related amino acids can reduce the allodynic and hyperalgesic action of STR or BIC in mice.