Abstract
S-(+)-Dicentrine is an aporphinic alkaloid found in several plant species, mainly from Lauraceae family, which showed significant antinociceptive activity in an acute model of visceral pain in mice. In this work, we extended the knowledge on the antinociceptive properties of S-(+)-dicentrine and showed that this alkaloid also attenuates mechanical and cold hypersensitivity associated with cutaneous inflammation induced by Complete Freund’s Adjuvant in mice. Given orally, S-(+)-dicentrine (100 mg/kg) reversed CFA-induced mechanical hypersensitivity, evaluated as the paw withdrawal threshold to von Frey hairs, and this effect lasted up to 2 hours. S-(+)-Dicentrine also reversed CFA-induced cold hypersensitivity, assessed as the responses to a drop of acetone in the injured paw, but did not reverse the heat hypersensitivity, evaluated as the latency time to paw withdrawal in the hot plate (50°C). Moreover, S-(+)-dicentrine (100 mg/kg, p.o.) was effective in inhibit nociceptive responses to intraplantar injections of cinnamaldehyde, a TRPA1 activator, but not the responses induced by capsaicin, a TRPV1 activator. When administered either by oral or intraplantar routes, S-(+)-dicentrine reduced the licking time (spontaneous nociception) and increased the latency time to paw withdrawal in the cold plate (cold hypersensitivity), both induced by the intraplantar injection of cinnamaldehyde. Taken together, our data adds information about antinociceptive properties of S-(+)-dicentrine in inflammatory conditions, reducing spontaneous nociception and attenuating mechanical and cold hypersensitivity, probably via a TRPA1-dependent mechanism. It also indicates that S-(+)-dicentrine might be potentially interesting in the development of new clinically relevant drugs for the management of persistent pain, especially under inflammatory conditions.
Highlights
Pain is normally a transitory unpleasant sensation subsequent to a noxious or potentially injurious stimulus, acting as a warning system for tissue protection against injuries
Statistical Analysis Results are presented as mean 6 S.E.M. and the data were analyzed by one-way analysis of variance (ANOVA) followed by Student-Newman-Keuls post hoc test, except Complete Freund’s Adjuvant (CFA)-induced chronic inflammatory pain that was analyzed by two-way ANOVA followed by Bonferroni post hoc test
Capsaicin and Cinnamaldehyde-induced Nociception Since S-(+)-dicentrine reduced hypersensitivity to cold, but not to heat, we further investigated if the thermo-transient receptor potential (TRP) (TRPV1 and TRPA1 ion channels) would be involved in on its effect
Summary
Pain is normally a transitory unpleasant sensation subsequent to a noxious or potentially injurious stimulus, acting as a warning system for tissue protection against injuries. It is a complex experience that involves the transduction of noxious environmental stimuli, and cognitive and emotional processing by the brain [1,2]. Some circumstances, such as inflammatory or neuropathic conditions, may lead to alterations of the pain pathway, leading to hypersensitivity, and the pain becomes chronic and debilitating. The transient receptor potential (TRP) ion channels appear to be molecular gateways in the sensory system [4]. In the field of pain, the subset of thermo-TRPs, mainly TRPV1 and TRPA1, seems to be important for initiation and maintenance of sensory nerve impulses that lead to nociception [5]
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