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 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.
Bereiter
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Department of Neuroscience, Brown University School of Medicine, 222 Nursing Arts Building, Rhode Island Hospital, Providence, USA. dbereiter@lifespan.org
Bereiter
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D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology*; D009149:Mustard Plant; D009292:Narcotic Antagonists; D010146:Pain / Q000139:chemically induced / Q000473:pathology; D010936:Plant Extracts; D010938:Plant Oils; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013704:Temporomandibular Joint / Q000293:injuries* / Q000473:pathology; D014279:Trigeminal Nucleus, Spinal / Q000187:drug effects* / Q000473:pathology
D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D010936:Plant Extracts; D010938:Plant Oils; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D009020:Morphine; C027793:mustard oil