Pain fiber anesthetic reduces brainstem Fos after tooth extraction

J Dent Res. 2013 Nov;92(11):1005-10. doi: 10.1177/0022034513505620. Epub 2013 Sep 20.

Abstract

We recently demonstrated that pain-sensing neurons in the trigeminal system can be selectively anesthetized by co-application of QX-314 with the TRPV1 receptor agonist, capsaicin (QX cocktail). Here we examined whether this new anesthetic strategy can block the neuronal changes in the brainstem following molar tooth extraction in the rat. Adult male Sprague-Dawley rats received infiltration injection of anesthetic 10 min prior to lower molar tooth extraction. Neuronal activation was determined by immunohistochemistry for the proto-oncogene protein c-Fos in transverse sections of the trigeminal subnucleus caudalis (Sp5C). After tooth extraction, c-Fos-like immunoreactivity (Fos-LI) detected in the dorsomedial region of bilateral Sp5C was highest at 2 hrs (p < .01 vs. naïve ipsilateral) and declined to pre-injury levels by 8 hrs. Pre-administration of the QX cocktail significantly reduced to sham levels Fos-LI examined 2 hrs after tooth extraction; reduced Fos-LI was also observed with the conventional local anesthetic lidocaine. Pulpal anesthesia by infiltration injection was confirmed by inhibition of the jaw-opening reflex in response to electrical tooth pulp stimulation. Our results suggest that the QX cocktail anesthetic is effective in reducing neuronal activation following tooth extraction. Thus, a selective pain fiber 'nociceptive anesthetic' strategy may provide an effective local anesthetic option for dental patients in the clinic.

Keywords: QX-314; capsaicin; central sensitization; lidocaine; orofacial pain; trigeminal caudal nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Combined / administration & dosage*
  • Anesthetics, Local / administration & dosage*
  • Animals
  • Brain Stem / drug effects*
  • Capsaicin / administration & dosage*
  • Dental Pulp / drug effects
  • Dental Pulp / innervation
  • Electric Stimulation
  • Electromyography
  • Lidocaine / administration & dosage
  • Lidocaine / analogs & derivatives*
  • Male
  • Mandibular Nerve / drug effects
  • Masticatory Muscles / drug effects
  • Molar / surgery
  • Neural Pathways / drug effects
  • Neurons, Afferent / drug effects
  • Nociceptors / drug effects*
  • Proto-Oncogene Proteins c-fos / analysis
  • Proto-Oncogene Proteins c-fos / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Reflex / drug effects
  • Sensory System Agents / administration & dosage*
  • Time Factors
  • Tooth Extraction*
  • Trigeminal Caudal Nucleus / drug effects*

Substances

  • Anesthetics, Combined
  • Anesthetics, Local
  • Proto-Oncogene Proteins c-fos
  • Sensory System Agents
  • QX-314
  • Lidocaine
  • Capsaicin