Using in vivo microdialysis in the dorsal spinal cord of the rat, we have previously observed increases in glutamate and aspartate during exposure to a noxious stimulus. The present investigation was designed to determine whether these increases may be mediated by substance P. Infusion of 1 mM of substance P in the dialysis fluid increased the concentrations of glutamate and aspartate, similar to the response seen during noxious stimulation. In addition, substance P also increased the concentrations of the inhibitory amino acids glycine and taurine. Calcitonin gene-related peptide, previously shown to enhance substance P-induced biting and scratching behavior, produced no effect on amino acid release by itself but potentiated the apparent release of taurine by substance P. To assess the importance of substance P-induced amino acid release in sensory processing, we examined the influence of taurine and of excitatory amino acid antagonists on the biting and scratching behavior produced by excitatory amino acids and substance P. Taurine selectively inhibited only substance P-induced biting and scratching while excitatory amino acid antagonists inhibited only excitatory amino acid-induced behavior. To further explore the ability of taurine to inhibit the substance P-induced behavior, 3 tests of nociception were then used. Pretreatment with taurine inhibited the nociceptive-related writhing behavior produced by an intraperitoneal injection of acetic acid in mice but failed to alter the latency of response in the hot plate or tail flick assay. These results indicate that substance P release during nociception may mediate the release of glutamate and aspartate but that these excitatory amino acids do not appear to be involved in substance P-induced biting and scratching behavior. The selective antinociceptive effect of taurine on chemical, but not thermal, tests of nociception suggests that its release in response to substance P and enhanced release following calcitonin gene-related peptide may be important in an endogenously evoked analgesia.
- Calcitonin gene-related peptide
- Excitatory amino acids
- Substance P