Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology
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Nihon Shinkei Seishin Yakurigaku Zasshi · Nov 2008
Review[Difference in tolerance to anti-hyperalgesic effect and its molecular mechanisms between chronic treatment with morphine, fentanyl and oxycodone in a chronic pain-like state].
In the present study, we demonstrated that repeated treatment with fentanyl, but not morphine or oxycodone, causes a rapid desensitization to its ability to block the hyperalgesia associated with the attenuation of mu-opioid receptor resensitization in mice in a chronic pain-like state. In contrast, no such effect was noted in beta-endorphin knockout mice under the chronic pain-like conditions. On the assumption that beta-endorphin might be released within the spinal cord under pain-like conditions, we further examined whether beta-endorphin could be responsible for a desensitization and resensitization of fentanyl under the chronic pain. ⋯ In the presence of beta-endorphin, the internalized mu-opioid receptor induced by fentanyl, but not oxycodone, remained within the cytosolic component even after washing out. The findings suggest that beta-endorphin could attenuate the resensitization of mu-opioid receptors. This phenomenon may explain the high degree of tolerance to fentanyl that develops with hyperalgesia caused by a chronic pain-like state.
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Nihon Shinkei Seishin Yakurigaku Zasshi · Feb 2008
Case Reports[H magnetic resonance spectroscopy investigation of the anterior cingulate cortex and prefrontal cortex in chronic pain patients].
We investigated the absolute concentration of N-acetylaspartate (NAA) in the anterior cingulated cortex (ACC), and prefrontal cortex (PFC) in chronic pain patients by proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS was performed with a 1.5T MR system on a voxel in the thalamus, ACC, and PFC bilaterally, in 48 chronic pain patients and 23 normal control subjects. We measured the absolute concentration of NAA using an LC-Model. There were 12 patients whose NAA concentration in the ACC or PFC was significantly, lower than the mean NAA concentration of the normal control subjects. Ten of these 12 patients needed a psychological approach. 1H-MRS suggests that NAA concentration in the ACC or PFC is associated with the necessity of a psychological approach. 1H-MRS may serve as a useful non-invasive tool for evaluating neural activity of the thalamus, anterior cingulated cortex, and prefrontal cortex in chronic pain patients.
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Although epilepsy was believed to have the highest incidence in childhood, recent epidemiologic studies revealed that the incidence increases markedly in elderly. At least 1% of elderly people are estimated to have epilepsy. Cerebrovascular disease is the most common underlying cause although 25% of new onset geriatric epilepsy cases have no obvious etiology. ⋯ Factors complicating the treatment of geriatric epilepsy include comorbidities, drug interactions due to polytherapy, and aging-related changing of pharmacokinetics. Individualization of dosage and avoidance of unnecessary polypharmacy are essential for safe utilization of anti-epileptic drugs. New generation drugs such as gabapentin and levetiracetam are better tolerated for elderly people.
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Nihon Shinkei Seishin Yakurigaku Zasshi · Nov 2006
Differences in tolerance to anti-hyperalgesic effects between chronic treatment with morphine and fentanyl under a state of pain.
The present study was undertaken to investigate the possible change in anti-hyperalgesic effect following repeated treatment with morphine or fentanyl using the dose to improve the thermal hyperalgesia under an inflammatory pain-like state. The anti-hyperalgesic effect induced by fentanyl in complete Freund's adjuvant (CFA)-pretreated mice rapidly disappeared during the consecutive administration of fentanyl, whereas morphine preserved its potency of anti-hyperalgesic effect. In addition, repeated treatment with fentanyl, but not morphine, resulted in the increase in levels of phosphorylated-mciro-opioid receptor (MOR) associated with the enhanced inactivation of protein phosphatase 2A and the reduction in Rab4-dependent MOR resensitization. ⋯ Furthermore, there was no significant difference between morphine and fentanyl in either antinociceptive effect or G-protein activation in mice partially lacking MOR-1B, which shows a greater resistance to agonist-induced desensitization than for other MOR subtypes. These findings point out the possibility that the chronic treatment with fentanyl may cause the different modulation from chronic treatment with morphine on either the internalization or resensitization of MORs in the spinal cord under a pain-like state. The present data provide the first evidence for the mechanism underlying the development of tolerance to fentanyl-induced anti-hyperalgesic effect under chronic pain.
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Nihon Shinkei Seishin Yakurigaku Zasshi · Jan 2006
[Joint meeting of 28th annual meeting of the Japanese Society of Biological Psychiatry, 36th annual meeting of the Japanese Society of Neuropsychopharmacology, 49th annual meeting of the Japanese Society of Neurochemistry. Nagoya, Japan. September 14-26, 2006. Program and Abstracts].