Electro-stimulatory forms of therapy can reduce angina that arises from activation of cardiac nociceptive afferent fibers during transient ischemia. This study sought to determine the effects of electrical stimulation of left thoracic vagal afferents (C8-T1 level)on the release of putative nociceptive (substance P; SP) and analgesic (dynorphin;DYN) peptides in the dorsal horn at the T4 spinal level during coronary artery occlusion (CoAO) in urethane anesthetized Sprague-Dawley rats. Release of DYN and SP was measured using antibody-coated microprobes. While DYN and SP had a basal release, occlusion of the left anterior descending coronary artery only affected SP release, causing an increase from lamina I-VII. Left vagal stimulation increased DYN release, inhibited basal SP release and blunted the CoAO-induced release of SP. DYN release reflected activation of descending pathways in the thoracic spinal cord, since vagal afferent stimulation still increased the release of DYN after bilateral dorsal rhizotomy of T2-T5. These results indicate that electro-stimulatory therapy, using vagal afferent excitation, may induce analgesia in part via inhibition of the release of SP in the spinal cord, possibly through a DYN-mediated neuronal interaction.