Pain
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Hydrogen sulfide (H2S), a gasotransmitter, facilitates membrane currents through T-type Ca2+ channels, and intraplantar (i.pl.) administration of NaHS, a donor of H2S, causes prompt hyperalgesia in rats. In this context, we asked whether intrathecal (i.t.) administration of NaHS could mimic the hyperalgesic effect of i.pl. NaHS in rats, and then examined if Cav3.2 isoform of T-type Ca2+ channels contributed to the pro-nociceptive effects of i.t. and i.pl. ⋯ Repeated i.t. administration of antisense oligodeoxynucleotides (ODNs) targeting rat Cav3.2, but not mismatch ODNs, caused silencing of Cav3.2 protein in the dorsal root ganglia and spinal cord, and then attenuated the hyperalgesia induced by either i.t. or i.pl. NaHS. Our findings thus establish that spinal and peripheral NaHS/H2S activates or sensitizes Cav3.2 T-type Ca2+ channels expressed in the primary afferents and/or spinal nociceptive neurons, leading to sensitization of nociceptive processing and hyperalgesia.
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Randomized Controlled Trial Controlled Clinical Trial
No evidence for the development of acute tolerance to analgesic, respiratory depressant and sedative opioid effects in humans.
It is widely accepted that chronic opioid therapy is associated with the development of pharmacological tolerance. More controversial is the question as to whether acute opioid administration can result in "acute tolerance." The aim of this double-blind, placebo-controlled study in thirty-six healthy human volunteers was to examine whether a 3-h intravenous infusion delivering two different but clinically relevant doses of the mu-opioid receptor agonist remifentanil would result in tolerance to analgesic, respiratory depressant and/or sedative opioid effects. The blood remifentanil concentration versus opioid effect relationship was determined before and after the 3-h infusion. ⋯ Neither dose of remifentanil produced detectable tolerance to any of the measured opioid effects following a 3-h infusion. The study was adequately powered to detect a decrease in potency of 5-24% for analgesia, 20-48% for respiratory depression, and 32% for sedative effects. These results suggest that short-term administration of clinically useful doses of remifentanil is not associated with the development of significant tolerance to analgesic, respiratory depressant, or sedative opioid effects.
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The objective of our study is to evaluate the detection capacity of Colour Duplex Scanning (CDS) in helping to diagnose Pudendal Neuralgia (PNa) by Pudendal Nerve Entrapment (PNE). This technique is being compared to complete Neurological Criteria (NC) based on Diagnostic Score (DS) and Electroneuromyography (ENMG) and secondly, to the results of surgery. This is a prospective study, on a consecutive series of 96 unselected patients evaluated by both CDS and NC. ⋯ Currently, there is no gold standard that can diagnose PNa by PNE with certainty. CDS is a non-invasive technique, demonstrating high diagnostic value to confirm PNE. In this study, we determined a new objective diagnostic criterion, the Pudendal Artery Ratio (PAR), which is very strong at diagnosing PNE but needs to be validated by further studies.