resiniferatoxin

Resiniferatoxin (RTX) is a natural product and ultrapotent agonist of the vanilloid receptor TRPV1. It is one of the most potent capsaicin analogs and was first isolated from the resin spurge Euphorbia resinifera. RTX is used primarily as a research tool due to its extreme potency and selectivity for TRPV1-expressing nociceptive neurons.

RTX binds to TRPV1 channels on pain-sensing neurons, causing a sustained calcium influx that leads to functional silencing or ablation of the affected nerve terminals. Because of its high potency, very small amounts can produce long-lasting effects, and repeated exposure tends to enhance these outcomes. This mechanism underpins RTX’s role in studying pain signaling and, in experimental and early clinical settings, in attempts to achieve targeted analgesia.

In research and limited clinical contexts, RTX has been explored as a means to selectively disable pain-sensing nerves through local or intrathecal administration to treat chronic or cancer-related pain. While the approach can yield substantial analgesia, safety concerns—such as potential neurotoxicity to sensory neurons, loss of protective sensation, and off-target effects—have tempered enthusiasm, and no RTX-based therapy has been approved for general use.

RTX remains a valuable tool in neuroscience for mapping TRPV1-expressing neurons and investigating the mechanisms of nociception and pain modulation. Its extreme potency and selective action on TRPV1 make it central to preclinical studies aiming to develop targeted, durable analgesic strategies.