Effects of repeated cold stress on aversive responses produced by intrathecal excitatory amino acids in rats.

We previously demonstrated the involvement of spinal glutamatergic system in repeated cold stress (RCS)-induced hyperalgesia. In the present experiments, to estimate the involvement of an enhancement of responsiveness to endogenously released glutamate in RCS-induced hyperalgesia, we examined the effects of RCS on behavioral nociceptive responses (biting or licking the hind paws and the tail) produced by intrathecal injections of selective agonists at subtypes of glutamate receptor, N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and kainate, in rats. The exposure of rats to RCS significantly intensified the behavioral responses produced by intrathecal NMDA (1 nmol/rat) in comparison to the control rats. The increase in the behavioral response of the RCS rats to AMPA was significant at a dose of 1 nmol/rat of AMPA as compared to the control rats. A significant increase in aversive response over control rats was not seen when kainate (0.3--nmol/rat) was injected into the spinal subarachnoid space of the RCS rats. These results suggest that RCS induces an enhancement of transmission mediated by endogenously released glutamate through NMDA and non-NMDA (especially AMPA) receptors in the spinal dorsal horn.