Pharmacology
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In order to further elucidate the mechanism(s) of action of analgesic and antihyperalgesic nefopam, its interactions with the transient receptor potential vanilloid subtype 1 (TRPV1) were investigated. In sensory neurons of rat embryos, dorsal root ganglion (DRG) in culture, nefopam (3-30 mumol/l) and capsazepine (TRPV1 antagonist, 10 mumol/l) prevented intracellular calcium elevation and calcitonin gene-related peptide release induced by vanilloid agonist capsaicin. ⋯ In vivo, nefopam (0.5 and 2 mg/kg, i.v.) and capsazepine (40 mg/kg, i.p.) reduced the licking response due to intraplantar injection of capsaicin in mice. These findings suggest that nefopam exerts its analgesic and antihyperalgesic effects through multiple mechanisms including blockade of TRPV1 in addition to voltage-dependent calcium channels in the DRG.
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Review
Meeting the challenges of opioid-induced constipation in chronic pain management - a novel approach.
Opioid analgesics are the cornerstone of pain management for moderate-to-severe cancer pain and, increasingly, chronic noncancer pain. Despite proven analgesic efficacy, the use of opioids is commonly associated with frequently dose-limiting constipation that seriously impacts on patients' quality of life. Agents currently used to manage opioid-induced constipation (OIC), such as laxatives, do not address the underlying opioid receptor-mediated cause of constipation and are often ineffective. ⋯ A novel approach for selectively and locally antagonizing the gastrointestinal effects of opioids involves the coadministration of a mu-opioid receptor antagonist with negligible systemic availability, such as oral naloxone. Combination therapy with prolonged-release (PR) oxycodone plus PR naloxone has been shown to provide effective analgesia while preventing or reducing constipation. The current article highlights this novel strategy in its potential to significantly improve the quality of life of patients suffering from chronic pain, affording patients the benefit of full analgesia, without the burden of OIC.
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Randomized Controlled Trial Comparative Study
Clinical equivalence of controlled-release oxycodone 20 mg and controlled-release tramadol 200 mg after surgery for breast cancer.
To assess clinical equivalence of 20 mg controlled-release oxycodone (Oxygesic; Mundipharma, Limburg, Germany) and 200 mg controlled-release tramadol (Tramal long; Grunenthal, Aachen, Germany) on a 12-hour dosing schedule in a randomized, double-blinded study of 54 ASA I-III physical status (American Society of Anesthesiologists classification of physical status) patients undergoing surgery for breast cancer. ⋯ 20 mg controlled-release oxycodone is clinically equivalent to 200 mg controlled-release tramadol for postoperative analgesia after surgery for breast cancer.
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Comparative Study
Differential analgesic effects of a mu-opioid peptide, [Dmt(1)]DALDA, and morphine.
H-Dmt-D-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA), a highly selective micro-opioid peptide, is potently analgesic after systemic and intrathecal administration but is less potent given intracerebroventricularly. This study was performed to further characterize the analgesic effects of [Dmt(1)]DALDA. ⋯ Systemic [Dmt(1)]DALDA has a unique analgesic property clearly different from that of morphine and it has a propensity to produce spinal analgesia.
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Comparative Study
Characterization of two models of drug-induced constipation in mice and evaluation of mustard oil in these models.
Although it is known that both clonidine and loperamide cause delayed colonic transit in mice, these models of drug-induced experimental constipation have not yet been fully characterized. Therefore, the aims of this study were to validate the clonidine- and loperamide-induced delays of colonic transit in mice as models of atonic and spastic constipation, respectively, and to evaluate the effect of mustard oil, a TRPA1 agonist, in both models. Colonic transit was evaluated in mice by determining the time needed to evacuate a bead inserted into the distal colon. ⋯ Atropine, an antispastic drug, improved the loperamide-induced delay, but did not affect the clonidine-induced delay. Mustard oil accelerated the colonic transit dose-dependently in both models of drug-induced constipations. These results indicate that clonidine- and loperamide-induced delays in colonic transit are models of atonic and spastic constipation, respectively, and that mustard oil may be effective on both types of constipation.