Modulation of N-methyl-D-aspartate and (R,S)-α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) responses of spinal nociceptive neurons by a N-terminal fragment of substance P

The effects of an N-terminal fragment of substance P, substance P-(1-7) [SP-(1-7)], on the responses of dorsal horn nociceptive neurons to N-methyl-D-aspartate (NMDA) and (R,S)-α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) were tested by combined single-unit extracellular recordings/microiontophoresis. While SP-(1-7) had no effects when applied by itself, it was a potent and long-lasting modulator of both NMDA- and AMPA-mediated excitation of spinal dorsal horn nociceptive neurons. NMDA responses were transiently decreased (by an average of 36% of control at minimum) by SP-(1-7) followed by a more sustained increase (by 76% at maximum). In contrast, AMPA responses were only increased by SP-(1-7) (by 81% at maximum). It is hypothesized that the actions of SP-(1-7) on excitatory amino acid (EAA) responses of dorsal horn nociceptive neurons reflect a novel mechanism by which SP and EAAs interact to modulate pain transmission.