Chronic inflammation and estradiol interact through MAPK activation to affect TMJ nociceptive processing by trigeminal caudalis neurons

A. Tashiro, Keiichiro Okamoto, David A Bereiter

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) pathway plays a key role in mediating estrogen actions in the brain and neuronal sensitization during inflammation. Estrogen status is a risk factor in chronic temporomandibular muscle/joint (TMJ) disorders; however, the basis for this relationship is not known. The present study tested the hypothesis that estrogen status acts through the MAPK/ERK signaling pathway to alter TMJ nociceptive processing. Single TMJ-responsive neurons were recorded in laminae I-II at the spinomedullary (Vc/C1-2) junction in naïve ovariectomized (OvX) female rats treated for 2 days with high-dose (20 μg/day; HE2) or low-dose estradiol (2 μg/day; LE2) and after chronic inflammation of the TMJ region by complete Freund's adjuvant for 12-14 days. Intra-TMJ injection of ATP (1 mM) was used to activate Vc/C1-2 neurons. The MAPK/ERK inhibitor (PD98059, 0.01-1 mM) was applied topically to the dorsal Vc/C1-2 surface at the site of recording 10 min prior to each ATP stimulus. In naïve HE2 rats, low-dose PD98059 caused a maximal inhibition of ATP-evoked activity, whereas even high doses had only minor effects on units in LE2 rats. By contrast, after chronic TMJ inflammation, PD98059 produced a marked and similar dose-related inhibition of ATP-evoked activity in HE2 and LE2 rats. These results suggested that E2 status and chronic inflammation acted, at least in part, through a common MAPK/ERK-dependent signaling pathway to enhance TMJ nociceptive processing by laminae I-II neurons at the spinomedullary junction region.

Original languageEnglish (US)
Pages (from-to)1813-1820
Number of pages8
JournalNeuroscience
Volume164
Issue number4
DOIs
StatePublished - Dec 29 2009

Bibliographical note

Funding Information:
This study was supported by a grant from the NIDCR ( DE 12758 ).

Keywords

  • MAP kinase
  • estrogen
  • nociception
  • temporomandibular joint
  • trigeminal brainstem

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