Potentiation of a behavioural response in mice by spinal coadministration of substance P and excitatory amino acid agonists.

The functional interaction in the spinal cord between substance P and excitatory amino acid agonists was investigated. Behavioural responses were scored in mice after intrathecal administration of excitatory amino acid agonists and substance P, given separately or in combination. A strong potentiation of the effect was seen when substance P was coadministered with N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) or kainic acid (KA). The potentiation was blocked by the corresponding antagonists: the selective NMDA-receptor antagonist (+/-)-3- (2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the substance P analog, [D-Arg1,D-Trp7,9,Leu11]-substance P (Spantide). These findings indicate a functional interaction between substance P and glutamate in the dorsal horn of the spinal cord, compatible with the hypothesis that corelease of substance P and glutamate from primary afferent neurons may enhance nociception.