EFFECTS OF REPEATED COLD STRESS ON AVERSIVE RESPONSES PRODUCED BY INTRATHECAL EXCITATORY AMINO-ACIDS IN RATS

We previously demonstrated the involvement of spinal glutamatergic sys tem in repeated cold stress (RCS)-induced hyperalgesia. In the present experiments, to estimate the involvement of an enhancement of respons iveness to endogenously released glutamate in RCS-induced hyperalgesia , we examined the effects of RCS on behavioral nociceptive responses ( biting or licking the hind pans and the tail) produced by intrathecal injections of selective agonists at subtypes of glutamate receptor, N- methyl-D-aspartate (NMDA), pha-amino-3-hydroxy-5-methylisoxazole-4-pro pionate (AMPA) and kainate, in rats, The exposure of rats to RCS signi ficantly intensified the behavioral responses produced by intrathecal NMDA (1 nmol/rat) in comparison to the control rats. The increase in t he behavioral response of the RCS rats to AMPA was significant at a do se of 1 nmol/rat of AMPA as compared to the control rats. A significan t increase in aversive response over control rats was not seen when ka inate (0.3-3 nmol/rat) was injected into the spinal subarachnoid space of the RCS rats. These results suggest that RCS induces an enhancemen t of transmission mediated by endogenously released glutamate through NMDA and non-NMDA (especially AMPA) receptors in the spinal dorsal hor n.