Amplified Brain Processing of Dentoalveolar Pressure Stimulus in Persistent Dentoalveolar Pain Disorder Patients.

AIMS: (1) To determine the brain regions activated by dentoalveolar pressure stimulation in persistent dentoalveolar pain disorder (PDAP) patients, and (2) to compare these activation patterns to those seen in pain-free control subjects. METHODS: A total of 13 PDAP patients and 13 matched controls completed the study. Clinical pain characteristics and psychosocial data were collected. Dentoalveolar mechanical pain thresholds were determined with a custom-made device over the painful area for patients and were used as the stimulation level during functional magnetic resonance imaging (fMRI) data acquisition. Control subjects received two stimulation levels over matched locations during fMRI scanning: one determined (as above) that evoked equally subjective pain ratings matching those of patients (subjective-pain match) and another nonpainful stimulation level matching the average stimulus intensity provided to patients (stimulus-intensity match). Clinical and psychosocial data were analyzed using independent samples t tests, Mann-Whitney U test, and Spearman rank-order correlation coefficient. fMRI data were analyzed using validated neuroimaging software and tested using a general linear model. RESULTS: PDAP patients had greater anxiety (P<.0001) and depression scores (P=.001), more jaw function impairment (P<.0001), and greater social impact (P<.0001) than controls. No significant differences were found for brain activation spatial extent (PDAP X Controls subjective pain: P=.48; PDAP X Controls stimulus intensity: P=.12). Brain activations were significantly increased for PDAP patients compared to control subjects when matched to stimulus intensity in several regions related to the sensory-discriminative and cognitive components of pain perception, including the primary and secondary somatosensory cortices, inferior parietal lobule, insula, premotor cortex, prefrontal cortex, and thalamus. When matched to subjective pain ratings, increased brain activations were still present for PDAP patients compared to controls, although to a lesser extent. CONCLUSION: The present results suggest that dentoalveolar pressure is processed differently in the brain of PDAP patients, and the increased activation in several brain areas is consistent with amplified pain processing.

Effect of persistent monoarthritis of the temporomandibular joint region on acute mustard oil-induced excitation of trigeminal subnucleus caudalis neurons in male and female rats.

The effect of persistent inflammation of the temporomandibular (TMJ) region on Fos-like immunoreactivity (Fos-LI) evoked by acute noxious stimulation of the same or opposite TMJ was assessed in male and cycling female rats. Two weeks after inflammation of the TMJ by complete Freund's adjuvant (CFA, 25 microg) the selective small fiber excitant, mustard oil (MO, 20%), was injected into the arthritic or opposite TMJ under barbiturate anesthesia. MO stimulation of the arthritic TMJ increased Fos-LI ipsilateral, but not contralateral, to MO compared to naïve subjects in superficial laminae at the trigeminal subnucleus caudalis/upper cervical cord (Vc/C2) junction independent of sex hormone status. Unexpectedly, MO stimulation of the opposite TMJ in arthritic rats also produced a greater Fos-LI response ipsilateral to MO than naïve animals. Fos-LI produced in the dorsal paratrigeminal region (dPa5) and Vc/C2 junction after MO stimulation of the normal TMJ was significantly greater in proestrous than diestrous females or male monoarthritic rats. In contrast to naïve animals, Fos-LI was produced in deep laminae at the Vc/C2 junction ipsilateral to MO in CFA-treated animals independent of the site of prior CFA inflammation or sex hormone status. These results indicated that persistent monoarthritis of the TMJ region enhanced the excitability of trigeminal brainstem neurons to subsequent TMJ injury that occurred bilaterally in multiple regions of the lower trigeminal brainstem complex and depended on sex hormone status.

The NMDA receptor antagonist MK-801 reduces Fos-like immunoreactivity in central trigeminal neurons and blocks select endocrine and autonomic responses to corneal stimulation in the rat.

The N-methyl-D-aspartate (NMDA) receptor is implicated in multiple aspects of pain processing by the central nervous system. However, the role of NMDA receptors in the endocrine and autonomic aspects of nociception remains uncertain. The present study examined the influence of the NMDA receptor antagonist, MK-801 (0.02-2.0 mg/kg, intracarotid), on the adrenal and autonomic responses to corneal stimulation (mustard oil, 20% sol.) in barbiturate-anesthetized rats. Fos-like immunoreactivity (Fos-LI) evoked by corneal stimulation was quantified within the spinal trigeminal nucleus (Vsp) of MK-801 pretreated animals to assess activation of central trigeminal neurons. Corneal stimulation-evoked increases in the plasma concentrations of adrenocorticotropin (ACTH), epinephrine and norepinephrine were reduced dose-dependently by MK-801. Plasma ACTH also increased after moderate hemorrhage, a response that was not affected by MK-801. MK-801 did not reduce the magnitude of corneal stimulation-evoked increases in arterial pressure and heart rate; however, prestimulus arterial pressure was reduced by drug treatment. Fos-LI was distributed bimodally within the ipsilateral caudal Vsp: one peak of Fos-LI in the subnucleus interpolaris/caudalis transition region and a second peak within the superficial laminae of the subnucleus caudalis/upper cervical cord transition region. The magnitude of both peaks of Fos-LI was reduced dose-dependently by MK-801. These results indicate a significant contribution from NMDA receptors in control of select endocrine and autonomic responses that accompany trigeminal nociception and in activation of central trigeminal neurons that process corneal nociceptive input.