Enhancement of spinothalamic neuron responses to chemical and mechanical stimuli following combined micro-iontophoretic application of n-methyl-d-aspartic acid and substance P

Abstract

Ncreased responses of primate spinothalamic neurons following co-administration of n-methyl-d-aspartic acid (NMDA) and substance P (SP) by micro-iontophoresis. Wide dynamic range and high threshold STT neurons in laminae I-VI showed an increased frequency of discharges following application of NMDA which was characterized by a slow onset to peak discharge rate and a slow return to background levels of discharge. Combined application of NMDA with SP resulted in an enhancement of responses to NMDA that often long outlasted the administration of SP. This increase in response of the cells to NMDA was not produced by repeated application of NMDA alone or following combined application of NMDA with an SP analog. NMDA responses were reduced or prevented in all cases by co-application of an NMDA-receptor antagonist. Finally, long-lasting potentiation of NMDA responses by SP was paralleled by enhanced responses to mechanical stimulation of skin. It is proposed that a mechanism involving the combined synaptic release of excitatory amino acids and peptides leads to secondary hyperalgesia. ∗Correspondence to: W.D. Willis, Department of Anatomy and Neurosciences, Marine Biomedical Institute, 200 University Blvd., University of Texas Medical Branch, Galveston, TX 77550-2772, U.S.A. Submitted November 20, 1990; revised January 17, 1991; accepted January 28, 1991. © Lippincott-Raven Publishers....