Differential effects of N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists on the responses of rat spinal neurons with joint input.

In anaesthetized rats the involvement of N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the processing of innocuous and noxious sensory inflow from joints was assessed in 27 spinal dorsal horn neurons. Microionophoretic application of either the NMDA antagonists ketamine and D,L-2-amino-5-phosphonovalerate (AP5) or the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reduced the responses to noxious compression of the knee and ankle joint. By contrast, the responses to innocuous pressure were consistently reduced by CNQX but only exceptionally by NMDA antagonists. Therefore non-NMDA receptors are involved in the processing of innocuous and noxious mechanical stimuli applied to the normal joint whereas NMDA receptors are activated mainly by nociceptive input.