Resiniferatoxin: Nature’s Precision Medicine to Silence TRPV1-Positive Afferents

Abstract

Resiniferatoxin (RTX) is an ultrapotent capsaicin analog with a unique spectrum of pharmacological actions. The therapeutic window of RTX is broad, allowing for the full desensitization of pain perception and neurogenic inflammation without causing unacceptable side effects. Intravesical RTX was shown to restore continence in a subset of patients with idiopathic and neurogenic detrusor overactivity. RTX can also ablate sensory neurons as a “molecular scalpel” to achieve permanent analgesia. This targeted (intrathecal or epidural) RTX therapy holds great promise in cancer pain management. Intra-articular RTX is undergoing clinical trials to treat moderate-to-severe knee pain in patients with osteoarthritis. Similar targeted approaches may be useful in the management of post-operative pain or pain associated with severe burn injuries. The current state of this field is reviewed, from preclinical studies through veterinary medicine to clinical trials.

Pathogenic Mechanisms and Therapeutic Approaches in Obesity-Related Knee Osteoarthritis

“…Highly purified synthetic trans-capsaicin, which specifically targets TRPV1-containing pain nociceptors while sparing sensory fibers for touch or pressure, has shown a rapid and significant impact on WOMAC walking pain scores and a favorable safety profile [135,136]. An injectable form of RTX has recently been developed and given a 'breakthrough therapy' status by the United States Food and Drug Administration (FDA) [137]. It is currently being investigated for the treatment of knee OA pain in a Phase III clinical trial but preliminary results from the Phase IB trial showed that 83% of patients had a statistically significant, clinically meaningful decrease in the WOMAC walking pain score [138].…”