Involvement of substance P and excitatory amino acids in aversive behavior elicited by intrathecal capsaicin

The rat given an intrathecal injection of capsaicin (0.3–10 nmol/rat) through a lumbar puncture showed biting or licking the tail and hind paws. The substance P antagonist, CP-96,345 (3 nmol/rat), co-administered intrathecally with capsaicin (10 nmol/rat), caused a significant inhibition of the behavioral responses to capsaicin (10 nmol/rat). When co-administered intrathecally with the NMDA antagonist, 2-amino-5-phosphonovaleric acid (APV, 10 nmol/rat), the capsaicin (10 nmol/rat) -induced behavioral responses were significantly inhibited. A co-administration of the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 nmol/rat), resulted in a significant reduction of the behavioral responses produced by capsaicin (10 nmol/rat). Administration of the combination of two antagonists (CP-96,345 and either APV or CNQX, or APV and CNQX) more markedly inhibited the behavioral responses to capsaicin (10 nmol/rat) than when either antagonist was co-administered with capsaicin. The results suggest that aversive behaviors induced by intrathecal capsaicin are mediated not only by the activation of NK-1 receptors but also by that of NMDA and non-NMDA receptors.