Journal of pharmacological sciences
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Oxaliplatin, a platinum-based chemotherapy drug, frequently causes acute and chronic peripheral neuropathies including mechanical hyperalgesia. These adverse effects hinder anticancer therapy with the drug. In this study, we examined several drugs that might prevent oxaliplatin-induced peripheral neuropathy. ⋯ Moreover, oxaliplatin caused phosphorylation of cofilin protein in the spinal cord, which has been shown to be involved in the neuropathic hyperalgesia. This increased phosphorylation of cofilin was also attenuated by gabapentin treatment. These results suggest that gabapentin is useful for relieving oxaliplatin-induced mechanical hyperalgesia and that the pathogenic mechanisms of cold allodynia and mechanical hyperalgesia differ.
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Multicenter Study
Intravenous paracetamol as an antipyretic and analgesic medication: the significance of drug metabolism.
One prospective, open-label, non-randomized study was conducted in 100 patients to define the antipyretic and analgesic effect of a new intravenous formulation of 1 g of paracetamol; 71 received paracetamol for the management of fever and 29 received paracetamol for pain relief after abdominal surgery or for neoplastic pain. Serial follow-up measurements of core temperature and of pain intensity were done for 6 h. Additional rescue medications were recorded for 5 days. ⋯ Analgesia was achieved in 25 patients (86.4%) within a median time of 2 h. Serum levels of glucuronide-APAP were greater among non-responders to paracetamol. The presented results suggest that the intravenous formulation of paracetamol is clinically effective depending on drug metabolism.
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The circadian clock system in mammals drives many physiological processes including the daily rhythms of sleep-wake behavior, hormonal secretion, and metabolism. This system responds to daily environmental changes, such as the light-dark cycle, food intake, and drug administration. In this review, we focus on the central and peripheral circadian clock systems in response to drugs, food, and nutrition. We also discuss the adaptation and anticipation mechanisms of our body with regard to clock system regulation of various kinetic and dynamic pathways, including absorption, distribution, metabolism, and excretion of drugs and nutrients. "Chrono-pharmacology" and "chrono-nutrition" are likely to become important research fields in chrono-biological studies.
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G-protein-activated inwardly rectifying potassium (GIRK) channels are expressed in many tissues and activated by several Gi/o protein-coupled receptors, such as opioid and dopamine receptors, and thus are known to be involved in the modulation of opioid-induced analgesia, pain, and reward. We focused on a GIRK-channel subunit that plays a pivotal role in the brain, GIRK2, and investigated the contribution of genetic variations of the GIRK2 (KCNJ6) gene to individual differences in the sensitivity to opioid analgesia. In our initial linkage disequilibrium analysis, a total of 27 single-nucleotide polymorphisms (SNPs) were selected within and around the regions of the KCNJ6 gene. ⋯ The results were corroborated in further confirmatory study. Interestingly, this SNP was also found to be associated with sensitivity to both cold and mechanical pain, susceptibility to nicotine dependence, and successful smoking cessation. The results indicate that this SNP could serve as a marker that predicts sensitivity to analgesic and pain and susceptibility to nicotine dependence.
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The antinociceptive effect of morphine in the inflammatory pain state was described in the von Frey filament test using the complete Freund's adjuvant (CFA)-induced mouse inflammatory pain model. After an i.pl. injection of CFA, mechanical allodynia was observed in the ipsilateral paw. The antinociceptive effect of morphine injected s.c. and i.t. against mechanical allodynia was reduced bilaterally at 1 day and 4 days after the CFA pretreatment. ⋯ In contrast, the protein level of μ-opioid receptors at 1 day after CFA pretreatment was decreased in the ipsilateral side in the DRG but not the lumbar spinal cord. Single or repeated i.t. pretreatment with the protein kinase Cα (PKCα) inhibitor Ro-32-0432 completely restored the reduced morphine antinociception in the contralateral paw but only partially restored it in the ipsilateral paw in the inflammatory pain state. In conclusion, reduced morphine antinociception against mechanical allodynia in the inflammatory pain state is mainly mediated via a decrease in μ-opioid receptors in the ipsilateral side and via the desensitization of μ-opioid receptors in the contralateral side by PKCα-induced phosphorylation.