BackgroundWe previously demonstrated nociceptive discharges to be evoked by mechanical noxious stimulation in the prefrontal cortex (PFC). The nociceptive responses recorded in the PFC are conceivably involved in the affective rather than the sensory-discriminative dimension of pain. The PFC receives dense projection from the limbic system. Monosynaptic projections from the basolateral nucleus of the amygdala (BLA) to the PFC are known to produce long-lasting synaptic plasticity. We examined effects of high frequency stimulation (HFS) delivered to the BLA on nociceptive responses in the rat PFC.ResultsHFS induced long lasting suppression (LLS) of the specific high threshold responses of nociceptive neurons in the PFC. Microinjection of N-methyl-D-aspartic acid (NMDA) receptor antagonists (2-amino-5-phosphonovaleric acid (APV), dizocilpine (MK-801)) and also metabotropic glutamate receptor (mGluR) group antagonists (α-methyl-4-carboxyphenylglycine (MCPG), and 2-[(1S,2S)-2-carboxycyclopropyl]-3-(9H-xanthen-9-yl)-D-alanine (LY341495)), prevented the induction of LLS of nociceptive responses. We also examined modulatory effects of dopamine (DA) on the LLS of nociceptive responses. With depletion of DA in response to 6-hydroxydopamine (6-OHDA) injection into the ipsilateral forebrain bundle, LLS of nociceptive responses was decreased, while nociceptive responses were normally evoked. Antagonists of DA receptor subtypes D2 (sulpiride) and D4 (3-{[4-(4-chlorophenyl) piperazin-1-yl] methyl}-1H-pyrrolo [2, 3-b] pyridine (L-745,870)), microinjected into the PFC, inhibited LLS of nociceptive responses.ConclusionsOur results indicate that BLA-PFC pathways inhibited PFC nociceptive cell activities and that the DA system modifies the BLA-PFC regulatory function.

BackgroundPsychological conditions affect pain responses in the human anterior cingulate cortex (ACC) according to brain imaging analysis. The rodent prefrontal cortex (PFC) including cingulate areas is also related to the affective dimension of pain. We previously reported PFC nociceptive responses inhibited by inputs from the amygdala, such as with dopamine (DA) D2 receptor (D2R) blockers, to show decreased effect on amygdala projections. In this study, we examined whether direct projections from the ventral tegmental area (VTA) to the PFC affect nociceptive responses in the PFC.ResultsHigh frequency stimulation (HFS, 50 Hz, 30 s) delivered to the VTA produced long-lasting suppression (LLS) of nociceptive responses in the rat PFC including cingulate and prelimbic areas. Nociceptive responses evoked by mechanical pressure stimulation (2 s duration at 500 g constant force) applied to the tails of urethane-anesthetized rats were recorded using extracellular unit recording methods in the PFC. HFS delivered to the VTA, which has been reported to increase DA concentrations in the PFC, significantly suppressed nociceptive responses. The LLS of nociceptive responses persisted for about 30 minutes and recovered to the control level within 60 min after HFS. We also demonstrated local microinjection of a selective D2 agonist of DA receptors to induce LLS of mechanical nociceptive responses, while a D2 but not a D1 antagonist impaired the LLS evoked by HFS. In contrast, DA depletion by a 6-hydroxydopamine injection or a low concentration of DA induced by a κ-opiate receptor agonist injected into the VTA had minimal effect on nociceptive responses in the PFC.ConclusionHFS delivered to VTA inhibited nociceptive responses for a long period in PFC. DA D2R activation mediated by local D2 agonist injection also induced LLS of mechanical nociceptive responses. The mesocortical DA system may modify PFC nociceptive responses via D2 activity.

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Myasthenia gravis (MG) is an autoimmune disease of the skeletal neuromuscular junction, leading to a decreased number of postsynaptic acetylcholine receptors. Most MG patients complain of ocular muscle ptosis, diplopia, or both as initial symptoms. However, in extremely rare cases, MG initially presents with disturbed mouth closing. This paper describes a case of MG in a 41-year-old man who first consulted our department because of mouth closing insufficiency. At presentation, the patient's general condition appeared to be normal. He was able to open his mouth to a distance of 39 mm between the upper and lower central incisors. However, he could not bite more than 8 times, after which he needed to use his hand to close his mouth. There were no other symptoms such as temporomandibular disorder. We suspected MG and referred him to the Department of Internal Medicine of our center. Repetitive electromyography with low-frequency stimulation showed a typical decrement in the muscle action potential. The blood titer of anti-acetylcholine receptor antibody was 34 nmol/e. A thymoma was subsequently detected on chest CT. The patient was finally given a diagnosis of MG and received anticholinesterase agents. He was temporarily well. However, malaise gradually developed. After admission to our center, he suddenly had a myasthenic crisis, followed by cardiopulmonary arrest. The myasthenic crisis was managed by mechanical ventilation, immunoadsorption, and steroid pulse therapy, after he was successfully revived by cardiopulmonary resuscitation. Thereafter, he received additional treatment by extended thymectomy and post-irradiation.The patient has remained well, and there is no further mouth closing insufficiency. MG rarely presents with symptoms associated with the masticatory muscles. We should include MG in thedifferential diagnosis when examining patients with mouth closing insufficiency.

Chemical peeling is a treatment method that destroys the epidermis and/or dermis with subsequent regeneration of new epidermis and dermis using a peeling agent. Phenol is one peeling agent that has been extremely effective in obtaining a complete response for gingival leukoplakia. In this report, we describe three cases of gingival leukoplakia that were treated with phenol peel, and we discuss the effects and applicable cases. All patients consulted our hospital in 2003 and refused surgical treatment, including laser surgery, so we performed chemical peeling using a phenolalcohol method that was previously reported for gingival melanin pigmentation. All cases achieved a complete response without local anesthesia or hospitalization. No patient felt pain at the time of application or post-treatment. None of the cases had a local recurrence or malignant transformation for approximately 69 months after the application of phenol peel. The use of a phenol peel may also be indicated for leukoplakia with dysplasia or other epithelial lesions. However, additional clinical studies that closely follow treated patients and further basic studies are still needed.