Morphine and NMDA receptor antagonism reduce c-fos expression in spinal trigeminal nucleus produced by acute injury to the TMJ region

David A. Bereiter, Dominique F. Bereiter

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Pain management in temporomandibular disorders (TMDs) often involves pharmacotherapy; however, the site of action for drugs that reduce TMD pain is not known. To determine possible central neural targets of analgesic drugs relevant in TMD pain, morphine or the N-methyl-D-aspartate receptor antagonist, MK-801, was given alone or in combination prior to TMJ injury. The number of neurons expressing the immediate early gene, c-fos, was quantified in the lower brainstem and upper cervical spinal cord as an index of neural activation. It was hypothesized that those neuronal groups most necessary for the sensory-discriminative aspects of acute TMJ injury should display the greatest reduction in c-fos expression after drug treatment. Barbiturate-anesthetized male rats were given morphine or MK-801 15 min prior to injection of mustard oil into the TMJ region. Morphine given centrally (i.c.v.) or peripherally (i.v.) caused a marked dose-related reduction in Fos-like immunoreactivity (Fos-LI) in laminae I-II at the middle portions of subnucleus caudalis (mid-Vc) and at the subnucleus caudalis/upper cervical spinal cord (Vc/C2) transition. Higher doses of morphine also reduced Fos-LI in the dorsal paratrigeminal region (dPa5) and at the subnucleus interpolaris/subnucleus caudalis (Vi/Vc-vl) transition. MK-801 given i.v. reduced Fos-LI only in laminae I-II at the Vc/C2 transition. Combined subthreshold doses of morphine and MK-801 reduced c-fos expression in the dPa5, mid-Vc, and the Vc/C2 transition region, below that predicted from the effects of either drug alone. These results suggest that neurons in laminae I-II of the mid-Vc and Vc/C2 transition and, to a lesser extent, in the dPa5 region play a critical role in mediating the sensory and/or reflex aspects of pain after acute injury to the TMJ region. (C) 2000 International Association for the Study of Pain.

Original languageEnglish (US)
Pages (from-to)65-77
Number of pages13
Issue number1-2
StatePublished - Mar 1 2000

Bibliographical note

Funding Information:
The authors thank Dr Harumitsu Hirata for helpful comments in preparing the manuscript. This study was supported in part by a grant from the NIDCR (DE-12758).

Copyright 2007 Elsevier B.V., All rights reserved.


  • Cervical spinal cord
  • Temporomandibular joint
  • Trigeminal spinal nucleus
  • c-fos gene


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