Journal of molecular neuroscience : MN
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Hyperbaric oxygen (HBO) treatment has been proven to be a promising candidate for protection of the nervous system after acute injury in animal models of neuropathic pain. The purposes of this study were to examine the antinociceptive response phase induced by HBO treatment in a model of neuropathic pain and to determine the dependence of the treatment's mechanism of alleviating neuropathic pain on the inhibition of spinal astrocyte activation. Neuropathic pain was induced in rats by chronic constriction injury of the sciatic nerve. ⋯ Repetitive HBO treatment led to a long-acting antinociceptive response phase and inhibited astrocyte activation. These results indicated that HBO treatment played a dual role in the aggravation and alleviation of neuropathic pain, though the aggravated pain effect (transient allodynia) was far less pronounced than the antinociceptive phase. Astrocyte inhibition and anti-inflammation may contribute to the antinociceptive effect of HBO treatment after nerve injury.
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In Morocco, Alzheimer's disease (AD) affects almost 30,000 individuals, and this number could increase to 75,000 by 2020. To our knowledge, the genes predisposing individuals to AD and predicting disease incidence remain elusive. In this study, we aimed to evaluate the genetic contribution of mutations in the amyloid precursor protein (APP) gene exons 16 and 17 to familial and sporadic AD cases. ⋯ Interestingly, only one novel splice mutation was detected in a family case. There is a strong correlation between clinical symptoms and genetic factors in Moroccan patients with a family history of AD. Therefore, mutations in APP gene exons 16 and 17 may eventually become genetic markers for AD predisposition.
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We studied the interaction of a single dose of different antidepressant medications with a single (acute) dose or implanted mini-pump (chronic) methadone administration in mice, using the hotplate assay. For the acute experiment, subthreshold doses of six antidepressant drugs were administered separately with a single dose of methadone. The addition of a subthreshold dose of desipramine or clomipramine to methadone produced significant augmentation of the methadone effect with each drug (p < 0.05). ⋯ Possible clinical implications of these findings are that while escitalopram, reboxetine and venlafaxine do not affect methadone's antinociception in mice and are safe to be given together with methadone when indicated, fluvoxamine, clomipramine and desipramine considerably augment methadone-induced effects and should be avoided in this population due to the risk of inducing opiate overdose. For the chromic experiment, when a subthreshold dose of either escitalopram, desipramine or clomipramine was injected to mice following 2 weeks of methadone administration with the mini-pump, none of the antidepressant drugs strengthened methadone's analgesic effect. Further studies are needed before possible clinical implications can be drawn.
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Treatment for bone cancer pain remains a clinical challenge due to a poor understanding of the underlying mechanisms. Protease-activated receptor 2 (PAR2), a receptor for inflammatory proteases, has been implicated in nociceptive signaling under both normal and pathologic pain states. However, little is known of the role of PAR2 in cancer-induced bone pain. ⋯ Immunohistochemical study revealed that the expression of PAR2 was significantly increased in large- and medium-sized dorsal root ganglia (DRG) neurons but not in small-sized neurons after Walker 256 inoculation. These results suggest that the increased expression of PAR2 in the DRG may contribute to the development of mechanical allodynia and thermal hyperalgesia associated with bone cancer rats. PAR2 might become a novel target for the treatment of pain in patients with bone cancer.