The Journal of Pain
Volume 9, Issue 6 , Pages 522-531, June 2008

Characterization of a Model of Chronic Orofacial Hyperalgesia in the Rat: Contribution of NAV 1.8

  • James R. Morgan

      Affiliations

    • Department of Pharmacology, The University of Iowa, Iowa City, Iowa.
  • ,
  • G.F. Gebhart

      Affiliations

    • The Center for Pain Research, University of Pittsburgh, Pittsburgh, Pennsylvania.
    • Corresponding Author InformationAddress reprint requests to Dr. G. F. Gebhart, Director, Center for Pain Research, University of Pittsburgh, W1444 BST, 200 Lothrop Street, Pittsburgh, PA 15213-2536.

Received 14 September 2007; received in revised form 31 December 2007; accepted 8 January 2008. published online 13 March 2008.

Abstract 

The purpose of this study was to develop and characterize a model of orofacial inflammatory hyperalgesia. Injection of complete Freund's adjuvant (CFA) into the upper lip/whisker pad of the rat produced significant and long-lasting thermal (≥14 days) and mechanical (≥28 days) hyperalgesia in the area of CFA injection. Both indomethacin and morphine, given systemically, significantly attenuated thermal hyperalgesia; the effect of morphine was shown to be opioid receptor-mediated. We also examined the contribution of the tetrodotoxin-resistant voltage-gated sodium channel Nav1.8 in CFA-produced orofacial mechanical hypersensitivity. Nav1.8 mRNA was increased ≥2.5-fold in trigeminal ganglion neurons 1 and 2 weeks after CFA treatment, and Nav1.8 protein was increased in the infraorbital nerve over a similar time course. The changes observed were time-dependent and had returned to baseline when examined 2 months after inflammation; there were no changes in Nav1.9 mRNA in trigeminal ganglion neurons after CFA treatment. In support of this, Nav1.8 antisense oligodeoxynucleotide treatment significantly attenuated CFA-produced mechanical hypersensitivity. These results document development of a model of inflammatory orofacial hyperalgesia, which, consistent with other reports, indicate a contribution of tetrodotoxin-resistant, voltage-gated sodium channel Nav1.8.

Perspective

Orofacial hypersensitivity develops postoperatively as a routine course of orofacial surgery, and mechanical allodynia is characteristic of temporomandibular joint disorder. The results described in this report are novel with respect to the duration of orofacial hypersensitivity produced and suggest that pharmacological targeting of the voltage-gated sodium channel Nav1.8 may be useful in managing hypersensitivity.

Key words: Orofacial pain, sodium channels, thermal hyperalgesia, mechanical hyperalgesia, orofacial pain model

To access this article, please choose from the options below

Login to an existing account or Register a new account.

  • Purchase this article for 31.50 USD (You must login/register to purchase this article)

    Online access for 24 hours. The PDF version can be downloaded as your permanent record.

  • Subscribe to this title

    Get unlimited online access to this article and all other articles in this title 24/7 for one year.

  • Claim access now

    For current subscribers with Society Membership or Account Number.

  • Visit SciVerse ScienceDirect to see if you have access via your institution.
 

 Editor's Note: Guest Editor for this article was Timothy Brennan, MD, PhD, Department of Anesthesia, University of lowa Hospitals and Clinics.

 Supported by grant R01 DA 02879.

PII: S1526-5900(08)00354-4

doi:10.1016/j.jpain.2008.01.326

The Journal of Pain
Volume 9, Issue 6 , Pages 522-531, June 2008