SUBSTANCE-P RELEASED ENDOGENOUSLY BY HIGH-INTENSITY SENSORY STIMULATION POTENTIATES PURINERGIC INHIBITION OF NOCICEPTIVE DORSAL HORN NEURONS INDUCED BY PERIPHERAL VIBRATION

To investigate the interaction at the spinal level of endogenously rel eased substance P with the effects of endogenously released adenosine, extracellular single-unit activity was recorded from dorsal horn neur ons in the anesthetized cat. Vibration to the skin inhibited on-going activity of nociceptive neurons; 20 mg/kg caffeine reversibly blocked this inhibition, indicating mediation via adenosine receptors. In half of the cases, this inhibition was potentiated by iontophoretic applic ation of substance P. High-intensity electrical stimulation to a senso ry nerve produced excitation which was blocked by an NK-1 (substance P ) receptor antagonist, implicating an endogenous neurokinin. When elec trical stimulation preceded the vibrational stimulus, the inhibitory e ffect of vibration was potentiated. Thus, we suggest that endogenous s ubstance P may potentiate the inhibitory response to endogenous adenos ine. The results have important implications for integration of inputs from different sensory modalities, especially as they relate to nocic eption and pain.