Intraarticular resiniferatoxin, a potent TRPV1 agonist, for treatment of osteoarthritic pain

Clinical investigations of resiniferatoxin (RTX) analgesia are currently ongoing for several human pain indications. RTX is an agonist of the TRPV1 receptor cation ion channel which is activated by capsaicin, heat, and inflammatory conditions. RTX injection at peripheral sites of pain generation will produce a chemo-inactivation of local nerve terminals and axons and block the transmission of nociceptive signals to spinal cord. Clinical human studies with RTX to treat osteoarthritis (OA) pain were preceded by extensive animal and cell system testing which revealed mechanisms of action, range of potentially treatable pain problems, and the safety and efficacy of this interventional analgesic agent. The present review concentrates on RTX, but also examines intraarticular (IA) capsaicin, a lower potency TRPV1 agonist, for the same indication. We review studies of RTX in human patients and canine veterinary subjects with OA pain. To date, results of several phase I clinical trials have only been reported in abstract form and these studies, despite their preliminary nature, will be examined herein. The present assessments indicate that RTX has strong therapeutic promise to be an innovative approach to medical management of pain relief in osteoarthritis and may be permissive to beneficial tissue remodeling.