Transient receptor potential vanilloid 1 (TRPV1)‐independent actions of capsaicin on cellular excitability and ion transport

Abstract

Capsaicin is a naturally occurring alkaloid derived from chili pepper that is responsible for its hot pungent taste. Capsaicin is known to exert multiple pharmacological actions, including analgesia, anticancer, anti‐inflammatory, antiobesity, and antioxidant effects. The transient receptor potential vanilloid subfamily member 1 (TRPV1) is the main receptor mediating the majority of the capsaicin effects. However, numerous studies suggest that the TRPV1 receptor is not the only target for capsaicin. An increasing number of studies indicates that capsaicin, at low to mid µM ranges, not only indirectly through TRPV1‐mediated Ca2+ increases, but also directly modulates the functions of voltage‐gated Na+, K+, and Ca2+ channels, as well as ligand‐gated ion channels and other ion transporters and enzymes involved in cellular excitability. These TRPV1‐independent effects are mediated by alterations of the biophysical properties of the lipid membrane and subsequent modulation of the functional properties of ion channels and by direct binding of capsaicin to the channels. The present study, for the first time, systematically categorizes this diverse range of non‐TRPV1 targets and discusses cellular and molecular mechanisms mediating TRPV1‐independent effects of capsaicin in excitable, as well as nonexcitable cells.

Are We Ready to Recommend Capsaicin for Disorders Other Than Neuropathic Pain?

“…Although several reviews have been published in recent years about the effect of capsaicin, capsinoids, and spicy foods on obesity [24,41,66,81,82], we are far from the confirmatory answer to if this action occurs in the general as well as in the affected population, what the magnitude of this action is, if it is safe, and what the optimal therapeutic dose and treatment duration are.…”