Central expression of the protooncogene c-fos was used to examine areas receiving noxious sensory input from the rat temporomandibular joint (TMJ). Fos-like immunoreactivity (Fos-LI) in the caudal brainstem was visualized 2 hours after unilateral injection of the small-fiber-specific excitant/inflammatory irritant mustard oil into the TMJ region. Control animals received injection of either mustard oil into the subcutaneous fascia overlying the masseter muscle or mineral oil vehicle into the TMJ region. In all groups, Fos-LI was consistently observed ipsilaterally in the spinal trigeminal nucleus and cervical dorsal horn and, bilaterally, in the nucleus of the solitary tract and the ventrolateral medulla. The expression of Fos-LI ipsilaterally in the paratrigeminal nucleus was variable. Within the trigeminal sensory complex, Fos-LI was restricted to subnucleus caudalis and the caudal portions of subnucleus interpolaris near the level of the obex. Approximately 12% of Fos-LI cells in subnucleus caudalis and in the cervical dorsal horn were found in laminae III-VI. Compared to TMJ mustard oil injection, mineral oil injection produced less Fos-LI at all rostrocaudal levels, whereas subcutaneous mustard oil injection produced less Fos-LI in caudal subnucleus caudalis but similar amounts in the cervical dorsal horn. Neither of these injections yielded significant ipsilateral responses in subnucleus caudalis, indicating that Fos-LI in this region following TMJ mustard oil injection could be ascribed solely to small-fiber stimulation in the deep TMJ region. The wide rostrocaudal distribution of Fos-LI within the caudal brainstem reflects the distribution of TMJ-responsive nociceptive neurons that may underlie the spread and referral of pain from the TMJ region.

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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.