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

Pain management in temporomandibular disorders (TMDs) often involves pharma cotherapy; however, the site of action for drugs that reduce TMD pain is no t known. To determine possible central neural targets of analgesic drugs re levant in TMD pain, morphine or the N-methyl-D-aspartate receptor antagonis t, MK-801, was given alone or in combination prior to TMJ injury. The numbe r 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 ac tivation. 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-an esthetized male rats were given morphine or MK-801 15 min prior to injectio n 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 immu noreactivity (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 do rsal paratrigeminal region (dPa5) and at the subnucleus interpolaris/subnuc leus 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 mor phine and MK-801 reduced c-fos expression in the dPa5, mid-Vc, and the Vc/C 2 transition region, below that predicted from the effects of either drug a lone. 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 critica l role in mediating the sensory and/or reflex aspects of pain after acute i njury to the TMJ region. (C) 2000 International Association for the Study o f Pain. Published by Elsevier Science B.V. All rights reserved.