Welcome to Flash Cards! These short features give you basic information about a therapeutic mechanism or core concept.
In sensory neurons, an important mode of action of the endocannabinoid anandamide is suppression of transient receptor potential vanilloid type 1 (TRPV1)-mediated hyperalgesia [1-3]. TRPV1 is a ligand-gated ion channel that mediates the nociceptive response to pain-triggering stimuli such as heat (e.g., touching a hot stove), acidic substances, and cytokines. Various cannabinoids tickle this receptor, and in doing so, moderate hyperalgesic transmission [4,5].
Phytochemical ligands of TRPV1 include capsaicin and cannabidiol (CBD)[4]. Binding of these substances leads to channel desensitization and effective modulation of sensory transmission. While capsaicin is well-characterized in this regard, many unanswered questions remain as to the location of the protein engaged by CBD, and what clinical dose would be required to recapitulate effective concentrations in the preclinical models.
References
[1] Zygmunt et al. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature. 1999;400:452–457.
[2] Catarina MJ et al. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science. 2000;288:306–313.
[3] Davis JD et al. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature. 2000;405:183–187.
[4] Bisogno T et al. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br. J. Pharmacol. 2001;134:845–852.
[5] Costa B et al. Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw. Naunyn Schmiedebergs Arch. Pharmacol. 2004;369:294–299.
Integrative Pharmacology 