Pharmacological research : the official journal of the Italian Pharmacological Society
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N-Palmitoyl-vanillamide (palvanil) is a non-pungent capsaicinoid, found in low amounts in Capsicum and shown to rapidly desensitize transient receptor potential vanilloid type-1 (TRPV1) channels to the action of capsaicin and to exert analgesic effects after local administration. We have investigated here if systemic administration of palvanil to mice causes two typical adverse events of TRPV1 agonists, i.e. profound changes in body temperature and bronchoconstriction, and if it can still produce effective inhibition of inflammatory and chronic pain in different experimental models. Varying doses of palvanil were tested subcutaneously and acutely on body temperature in vivo or, or as a bolus, on bronchopulmunary function ex vivo, in comparison with capsaicin. ⋯ Palvanil (0.5-2.5 mg/kg) abolished formalin-induced nocifensive behavior and strongly attenuated SNI-induced mechanical allodynia and thermal hyperalgesia and carrageenan-induced oedema and thermal hyperalgesia. Systemic administration of the non-pungent capsaicinoid, palvanil, produces, at least in mice, much less of those side effects typical of TRPV1 agonists (hypothermia and bronchoconstriction), whilst being very effective at reducing pain and oedema. Thus, palvanil might be developed further as a novel pharmacological treatment for chronic abnormal pain.