Modulation of TRPV1 channel function by natural products in the treatment of pain

Abstract

The capsaicin (vanilloid) receptor, TRPV1, is a heat-activated cation channel modulated by inflammatory mediators and contributes to acute and chronic pain. TRPV1 channel is one of the most researched and targeted mechanisms for the development of novel analgesics. Over the years, natural products have contributed enormously to the development of important therapeutic drugs used currently in modern medicine. A literature review was conducted using Medline, Google Scholar, and PubMed. Searching the literature resulted in listing 136 natural compounds that interacted with TRPV1 channel. These compounds were phytochemicals that belong to different chemical groups including vanilloids, flavonoids, alkaloids, terpenoids, terpenyl phenols, fatty acids, cannabinoids, sulfur_containing compounds, etc. Other natural TRPV1 modulators were of animal, fungal or bacterial origin. Some natural products were small agonists or antagonists of TRPV1. Others were protein venoms. Most in vitro studies utilized electrophysiological or calcium imaging techniques to study calcium flow through the channel using primary cultures of rat dorsal root and trigeminal ganglia. Other studies used hTRPV1 or rTRPV1 expressed in HEK239, CHO cells or Xenopus oocytes. In vivo studies concentrated on different pain models conducted mainly in mice and rats. In conclusion, natural products are highly diverse in their modulatory action on TRPV1. Many gaps in natural product research are present in distinguishing modality-specific from polymodal antagonists. Species' differences in TRPV1 functionality must be taken into account in any future study. Proceeding into clinical trials needs more efforts to discover potent TRPV1 antagonists devoid of hyperthermia, the main side effect.

Keywords: Antagonists; Capsaicin; Modality-specific; Natural products; TRPV1; Vanilloids.