Capsaicin-evoked iCGRP release from human dental pulp: A model system for the study of peripheral neuropeptide secretion in normal healthy tissue

Jill C. Fehrenbacher, Xiaoling X. Sun, Erin E. Locke, Michael A. Henry, Kenneth M. Hargreaves

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The mechanisms underlying trigeminal pain conditions are incompletely understood. In vitro animal studies have elucidated various targets for pharmacological intervention; however, a lack of clinical models that allow evaluation of viable innervated human tissue has impeded successful translation of many preclinical findings into clinical therapeutics. Therefore, we developed and characterized an in vitro method that evaluates the responsiveness of isolated human nociceptors by measuring basal and stimulated release of neuropeptides from collected dental pulp biopsies. Informed consent was obtained from patients presenting for extraction of normal wisdom teeth. Patients were anesthetized using nerve block injection, teeth were extracted and bisected, and pulp was removed and superfused in vitro. Basal and capsaicin-evoked peripheral release of immunoreactive calcitonin gene-related peptide (iCGRP) was analyzed by enzyme immunoassay. The presence of nociceptive markers within neurons of the dental pulp was characterized using confocal microscopy. Capsaicin increased the release of iCGRP from dental pulp biopsies in a concentration-dependent manner. Stimulated release was dependent on extracellular calcium, reversed by a TRPV1 receptor antagonist, and desensitized acutely (tachyphylaxis) and pharmacologically by pretreatment with capsaicin. Superfusion with phorbol 12-myristate 13-acetate (PMA) increased basal and stimulated release, whereas PGE2 augmented only basal release. Compared with vehicle treatment, pretreatment with PGE2 induced competence for DAMGO to inhibit capsaicin-stimulated iCGRP release, similar to observations in animal models where inflammatory mediators induce competence for opioid inhibition. These results indicate that the release of iCGRP from human dental pulp provides a novel tool to determine the effects of pharmacological compounds on human nociceptor sensitivity.

Original languageEnglish (US)
Pages (from-to)253-261
Number of pages9
JournalPain
Volume144
Issue number3
DOIs
StatePublished - Aug 1 2009
Externally publishedYes

Keywords

  • Analgesia
  • Calcitonin gene-related peptide
  • Capsaicin
  • Clinical trial
  • Dental pulp
  • Exocytosis
  • Human
  • MOR
  • Morphine
  • Neuropeptide release
  • Pain
  • Sensory neuron
  • TRPV1
  • Translational studies

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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