Tooth extraction-induced internalization of the substance P receptor in trigeminal nucleus and spinal cord neurons: Imaging the neurochemistry of dental pain

Mary Ann C. Sabino, Prisca Honore, Scott D. Rogers, David B. Mach, Nancy M. Luger, Patrick W. Mantyh

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Although pains arising from the craniofacial complex can be severe and debilitating, relatively little is known about the peripheral and central mechanisms that generate and maintain orofacial pain. To better understand the neurons in the trigeminal complex and spinal cord that are activated following nociceptive stimuli to the orofacial complex, we examined substance P (SP) induced internalization of substance P receptors (SPR) in neurons following dental extraction in the rat. Unilateral gingival reflection or surgical extraction of a rat maxillary incisor or molar was performed and tissues harvested at various time points post-extraction. Immunohistochemical analysis of brainstem and cervical spinal cord sections was performed using an anti-SPR antibody and confocal imaging. Both the number and location of neurons showing SPR internalization was dependent on the location and extent of tissue injury. Whereas extraction of the incisor induced internalization of SPR in neurons bilaterally in nucleus caudalis and the spinal cord, extraction of the molar induced strictly unilateral internalization of SPR-expressing neurons in the same brain structures. Minor tissue injury (retraction of the gingiva) activated SPR neurons located in lamina I whereas more extensive and severe tissue injury (incisor or molar extraction) induced extensive SPR internalization in neurons located in both laminae I and III-V. The rostrocaudal extent of the SPR internalization was also correlated with the extent of tissue injury. Thus, following relatively minor tissue injury (gingival reflection) neurons showing SPR internalization were confined to the nucleus caudalis while procedures which cause greater tissue injury (incisor or molar extraction), neurons showing SPR internalization extended from the interpolaris/caudalis transition zone through the C7 spinal level. Defining the population of neurons activated in orofacial pain and whether analgesics modify the activation of these neurons should provide insight into the mechanisms that generate and maintain acute and chronic orofacial pain.

Original languageEnglish (US)
Pages (from-to)175-186
Number of pages12
JournalPain
Volume95
Issue number1-2
DOIs
StatePublished - Jan 29 2002
Externally publishedYes

Keywords

  • Medullary dorsal horn
  • Neurokinin-1 receptor
  • Nociception
  • Orofacial pain

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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