The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Mar 2003
Novel expression of vanilloid receptor 1 on capsaicin-insensitive fibers accounts for the analgesic effect of capsaicin cream in neuropathic pain.
Here, we investigated the mechanism of the antihyperalgesic effect of capsaicin cream in the nerve injury-induced neuropathic pain model in mice. In naive mice, application of capsaicin cream onto footpad caused no significant changes in the thermal latency in contrast to the severe thermal hyperalgesia induced by a capsaicin ointment. On the other hand, application of the cream 3 h before test concentration dependently reversed both thermal and mechanical hyperalgesia observed after partial sciatic nerve injury in mice. ⋯ Finally, novel expression of VR1 receptors on neonatal capsaicin-insensitive neurons after nerve injury was confirmed by immunohistochemistry. The newly expressed VR1 receptors after nerve injury were mainly confined to A-fibers. Together, our results suggest that novel expression of capsaicin receptors in neuropathic condition contributes to the analgesic effects of the capsaicin cream.
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J. Pharmacol. Exp. Ther. · Mar 2003
Methylphenidate alters vesicular monoamine transport and prevents methamphetamine-induced dopaminergic deficits.
It has been hypothesized that high-dose methamphetamine treatment rapidly redistributes cytoplasmic dopamine within nerve terminals, leading to intraneuronal reactive oxygen species formation and well characterized persistent dopamine deficits. We and others have reported that in addition to this persistent damage, methamphetamine treatment rapidly decreases vesicular dopamine uptake, as assessed in purified vesicles prepared from treated rats; a phenomenon that may contribute to aberrant intraneuronal dopamine redistribution proposedly caused by the stimulant. Interestingly, post-treatment with dopamine transporter inhibitors protect against the persistent dopamine deficits caused by methamphetamine; however, mechanisms underlying this phenomenon have not been elucidated. ⋯ In addition, methylphenidate post-treatment reverses the acute decreases in vesicular dopamine content caused by methamphetamine treatment. Taken together, these findings suggest that methylphenidate prevents persistent methamphetamine-induced dopamine deficits by redistributing vesicles and the associated VMAT-2 protein and presumably affecting dopamine sequestration. These findings not only provide insight into the neurotoxic effects of methamphetamine but also mechanisms underlying dopamine neurodegenerative disorders, including Parkinson's disease.