Involvement of spinal NK2 and NMDA receptors in aversive behavior induced by intra-arterial injection of capsaicin

The spinal processing by which intra-arterial injection of capsaicin (CAP) induces vocalization response (VOR) was investigated in guinea pigs. Intrathecal pre-treatment with CP-96,345 (a selective NK1 receptor antagonist, 50 nmol) did not affect the CAP-induced VOR. However, significant attenuation of the VOR was observed by intrathecal pre-treatment with a selective NK2 receptor antagonist MEN-10.376 (40 nmol) accompanied with a significant change in the response modality. MK-801 [an N-methyl-D-aspartate (NMDA) receptor antagonist, 20 and 40 nmol] inhibited the CAP-induced VOR dose-dependently without affecting the response modalities. Furthermore, intrathecal co-treatment with 40-nmol MEN-10.376 and 40-nmol MK-801 resulted in a marked inhibitory effect on the VOR followed by a significant alteration of response modalities. Intrathecal pre-treatment with neurokinin A (NKA; a tachykifiin NK2 receptor agonist, 1 nmol) enhanced the CAP-induced VOR. These behavioral results suggested that spinal NK2 and NMDA receptors might have priority over NK1 receptors in the spinal processing of nociceptive information from the CAP-sensitive nociceptor. (C) 2001 Elsevier Science Inc. All rights reserved.