Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP (Transient Receptor Potential) super-family. It is a relatively underexplored member of the thermo-TRP sub-family (Figure 1), however, genetic mutations and use of gene knock-outs and selective pharmacological tools are helping to provide insights into its role and therapeutic potential. TRPV3 is highly expressed in skin, where it is implicated in skin physiology and pathophysiology, thermo-sensing and nociception.
View Article and Find Full Text PDFKappa opioid receptors and their endogenous neuropeptide ligand, dynorphin A, are densely localized in limbic and cortical areas comprising the brain reward system, and appear to play a key role in modulating stress and mood. Growing literature indicates that kappa receptor antagonists may be beneficial in the treatment of mood and addictive disorders. However, existing literature on kappa receptor antagonists has used extensively JDTic and nor-BNI which exhibit long-lasting pharmacokinetic properties that complicate experimental design and interpretation of results.
View Article and Find Full Text PDFIn humans, kappa opioid receptor agonists produce, among other effects, sedation and difficulty concentrating, suggesting that they may disrupt attention. The purpose of the present studies was therefore to evaluate the effects of kappa opioid receptor agonists on attention as assessed by a 5-choice serial reaction time task in rats. The kappa opioid receptor agonists (+)-U69,593 (0.
View Article and Find Full Text PDFA major purpose of the present studies was to determine the effects of varying the relative frequency, or bias, of stimulus presentation at different locations in a five-choice serial reaction time attention task. Training sessions were conducted in which the stimulus duration was held constant at 2 s and, initially, stimuli were presented with equal probability above each of the levers. During testing sessions, however, stimulus duration was either 0.
View Article and Find Full Text PDFThe purpose of the present study was to explore the analgesic effects of the low voltage-activated T-type Ca2+ channel blockers ethosuximide, trimethadione, and mibefradil in persistent and acute nociceptive tests. The anticonvulsant effects of the compounds were also determined in the intravenous pentylenetetrazol seizure model. Following intraperitoneal administration, ethosuximide and trimethadione dose-dependently reversed capsaicin-induced mechanical hyperalgesia.
View Article and Find Full Text PDFGroup II (mGluR2/3) metabotropic glutamate receptors have been implicated in the mechanisms of persistent pain states. In the present study, the effects of the selective group II metabotropic glutamate receptor agonists LY379268 and LY389795 were evaluated in the formalin test, carrageenan-induced thermal hyperalgesia and mechanical allodynia, and capsaicin-induced mechanical allodynia in rats. The agonists LY379268 and LY389795 produced dose-dependent decreases in formalin-induced behaviors that were antagonized by the mGlu2/3 receptor antagonist LY341495.
View Article and Find Full Text PDFThe purpose of the present studies was to compare anticonvulsant drugs with diverse mechanisms of action in a persistent pain model, the formalin test. In addition, the anticonvulsant effects of the compounds were determined in the threshold electroshock tonic seizure test and the 6-Hz limbic seizure test. The effects of the compounds were also determined on locomotor activity.
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