Noxious cutaneous thermal stimuli induce a graded release of endogenous substance P in the spinal cord: Imaging peptide action in vivo

Brian J. Allen, Scott D. Rogers, Joseph R. Ghilardi, Patrick M. Menning, Michael A. Kuskowski, Allan I. Basbaum, Donald A. Simone, Patrick W. Mantyh

Research output: Contribution to journalArticle

134 Scopus citations

Abstract

Dorsal root ganglia (DRG) neurons synthesize and transport substance P (SP) to the spinal cord where it is released in response to intense noxious 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 noxious heat (43°, 48°, and 55°C) and cold (10°, 0°, -10°, and -20°C) stimuli, but not innocuous warm (38°C) and cold (20°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 stimulus. Thus, with increasing stimulus intensities, both the total number of SPR+ lamina I neurons showing SPR internalization and the number of internalized SPR+ endosomes within each SPR immunoreactive neuron showed a significant increase. These data suggest that thermal stimuli induce a graded release of SP from primary afferent terminals and that agonist dependent receptor endocytosis provides evidence of a spatially and pharmacologically unique 'neurochemical signature' after specific somatosensory stimuli.

Original languageEnglish (US)
Pages (from-to)5921-5927
Number of pages7
JournalJournal of Neuroscience
Volume17
Issue number15
StatePublished - Aug 1 1997
Externally publishedYes

Keywords

  • Neurokinin-1
  • Nociception
  • Pain
  • Sensory neuron
  • Substance P receptor
  • Tachykinin

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Noxious cutaneous thermal stimuli induce a graded release of endogenous substance P in the spinal cord: Imaging peptide action in vivo'. Together they form a unique fingerprint.

  • Cite this

    Allen, B. J., Rogers, S. D., Ghilardi, J. R., Menning, P. M., Kuskowski, M. A., Basbaum, A. I., Simone, D. A., & Mantyh, P. W. (1997). Noxious cutaneous thermal stimuli induce a graded release of endogenous substance P in the spinal cord: Imaging peptide action in vivo. Journal of Neuroscience, 17(15), 5921-5927.