Spinal opioid analgesia: How critical is the regulation of substance P signaling?

Jodie A. Trafton, Catherine Abbadie, Serge Marchand, Patrick W Mantyh, Allan I. Basbaum

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Although opioids can reduce stimulus-evoked efflux of Substance P (SP) from nociceptive primary afferents, the consequences of this reduction on spinal cord nociceptive processing has not been studied. Rather than assaying SP release, in the present study we examined the effect of opioids on two postsynaptic measures of SP release, Fos expression and neurokinin-1 (NK-1) receptor internalization, in the rat. The functional significance of the latter was first established in in vitro studies that showed that SP-induced Ca2+ mobilization is highly correlated with the magnitude of SP-induced NK- 1 receptor internalization in dorsal horn neurons. Using an in vivo analysis, we found that morphine had little effect on noxious stimulus-evoked internalization of the NK-1 receptor in lamina I neurons. However, internalization was reduced when we coadministered morphine with a dose of an NK-1 receptor antagonist that by itself was without effect. Thus, although opioids may modulate SP release, the residual release is sufficient to exert maximal effects on the target NK-1 receptors. Morphine significantly reduced noxious stimulus-induced Fos expression in lamina I, but the Fos inhibition was less pronounced in neurons that expressed the NK-1 receptor. Taken together, these results suggest that opioid analgesia predominantly involves postsynaptic inhibitory mechanisms and/or presynaptic control of non-SP- containing primary afferent nociceptors.

Original languageEnglish (US)
Pages (from-to)9642-9653
Number of pages12
JournalJournal of Neuroscience
Volume19
Issue number21
StatePublished - Nov 1 1999
Externally publishedYes

Fingerprint

Neurokinin-1 Receptors
Substance P
Analgesia
Opioid Analgesics
Morphine
Neurokinin-1 Receptor Antagonists
Posterior Horn Cells
Neurons
Nociceptors
Spinal Cord

Keywords

  • Dorsal horn
  • Internalization
  • Intrathecal
  • Morphine
  • Nociception
  • Tachykinin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Trafton, J. A., Abbadie, C., Marchand, S., Mantyh, P. W., & Basbaum, A. I. (1999). Spinal opioid analgesia: How critical is the regulation of substance P signaling? Journal of Neuroscience, 19(21), 9642-9653.

Spinal opioid analgesia : How critical is the regulation of substance P signaling? / Trafton, Jodie A.; Abbadie, Catherine; Marchand, Serge; Mantyh, Patrick W; Basbaum, Allan I.

In: Journal of Neuroscience, Vol. 19, No. 21, 01.11.1999, p. 9642-9653.

Research output: Contribution to journalArticle

Trafton, JA, Abbadie, C, Marchand, S, Mantyh, PW & Basbaum, AI 1999, 'Spinal opioid analgesia: How critical is the regulation of substance P signaling?', Journal of Neuroscience, vol. 19, no. 21, pp. 9642-9653.
Trafton JA, Abbadie C, Marchand S, Mantyh PW, Basbaum AI. Spinal opioid analgesia: How critical is the regulation of substance P signaling? Journal of Neuroscience. 1999 Nov 1;19(21):9642-9653.
Trafton, Jodie A. ; Abbadie, Catherine ; Marchand, Serge ; Mantyh, Patrick W ; Basbaum, Allan I. / Spinal opioid analgesia : How critical is the regulation of substance P signaling?. In: Journal of Neuroscience. 1999 ; Vol. 19, No. 21. pp. 9642-9653.
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