NOXIOUS CUTANEOUS THERMAL STIMULI INDUCE A GRADED RELEASE OF ENDOGENOUS SUBSTANCE-P IN THE SPINAL-CORD - IMAGING PEPTIDE ACTION IN-VIVO

Dorsal root ganglia (DRG) neurons synthesize and transport substance P (SP) to the spinal cord where it is released in response to intense n oxious somatosensory stimuli. We have shown previously that SP release in vivo causes a rapid and reversible internalization of SP receptors (SPRs) in dorsal horn neurons, which may provide a pharmacologically specific image of neurons activated by SP. Here, we report that noxiou s heat (43 degrees, 48 degrees, and 55 degrees C) and cold (10 degrees , 0 degrees, -10 degrees, and -20 degrees C) stimuli, but not innocuou s warm (38 degrees C) and cold (20 degrees C) stimuli, applied to the hindpaw of anesthetized rats induce SPR internalization in spinal cord neurons that is graded with respect to the intensity of the thermal s timulus. Thus, with increasing stimulus intensities, both the total nu mber of SPR+ lamina I neurons showing SPR internalization and the numb er of internalized SPR+ endosomes within each SPR immunoreactive neuro n showed a significant increase. These data suggest that thermal stimu li induce a graded release of SP from primary afferent terminals and t hat agonist dependent receptor endocytosis provides evidence of a spat ially and pharmacologically unique ''neurochemical signature'' after s pecific somatosensory stimuli.