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• W1966635880 abstract "Capsaicin produces thermal allodynia in animals and humans by acting as an agonist at vanilloid receptor subtype 1 [VR1; also known as transient receptor potential vanilloid type 1 (TRPV1)]. VR1 receptors are widely distributed in the periphery (e.g., on primary afferent neurons). These studies examined the ability of loperamide (0.1–1 mg/kg s.c.; a μ-opioid agonist that is peripherally selective after systemic administration), in preventing and reversing thermal allodynia caused by topical capsaicin (0.004 M) in rhesus monkeys, within a tail withdrawal assay (<i>n</i> = 4; 38°C and 42°C; normally non-noxious thermal stimuli). The effects of loperamide were compared with those of the centrally penetrating μ-agonist, fentanyl (0.0032–0.032 mg/kg s.c.). We also characterized the allodynic effects of the endogenous VR1 agonist (“endovanilloid”), <i>N</i>-oleoyldopamine (OLDA; 0.0013–0.004 M). In this model, loperamide and fentanyl produced dose-dependent prevention of capsaicin-induced allodynia, whereas only fentanyl produced robust reversal of ongoing allodynia. Antagonism experiments with naltrexone (0.1 mg/kg s.c.) or its analog, methylnaltrexone (0.32 mg/kg s.c.), which does not readily cross the blood-brain barrier, suggest that the antiallodynic effects of loperamide and fentanyl were predominantly mediated by peripherally and centrally located μ-receptors, respectively. Loperamide and fentanyl (1 mg/kg and 0.032 mg/kg, respectively) also prevented OLDA (0.004 M)-induced allodynia. Up to the largest dose studied, loperamide was devoid of thermal antinociceptive effects at 48°C (a noxious thermal stimulus, in the absence of capsaicin). By contrast, fentanyl (0.01–0.032 mg/kg) caused dose-dependent antinociception in this sensitive thermal antinociceptive assay (a presumed centrally mediated effect). These studies show that loperamide, acting as a peripherally selective μ-agonist after systemic administration, can prevent capsaicin-induced thermal allodynia in primates in vivo, in the absence of thermal antinociceptive effects." @default.
• W1966635880 created "2016-06-24" @default.
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• W1966635880 date "2004-05-19" @default.
• W1966635880 modified "2023-09-23" @default.
• W1966635880 title "Antiallodynic Effects of Loperamide and Fentanyl against Topical Capsaicin-Induced Allodynia in Unanesthetized Primates" @default.
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• W1966635880 doi "https://doi.org/10.1124/jpet.104.068411" @default.
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