Resiniferatoxin

Resiniferatoxin (RTX, CAS No. 57444-62-9) is a highly selective, ultra-potent transient receptor potential vanilloid subtype 1 (TRPV1) agonist. By binding to and persistently opening the TRPV1 cation channel, it triggers Ca2+ influx, leading to chemical inactivation and desensitization of TRPV1-positive sensory nerve endings, thereby playing a central role in long-lasting analgesia and inhibition of neurogenic inflammation. It may also improve symptoms of overactive bladder, interstitial cystitis, colitis, and periodontal inflammation, without affecting motor function, proprioception, or mechanical pain transmission. Its analgesic potency is approximately 500-1000 times that of capsaicin (Capsaicin, CAS: 404-86-4, Cat. No.: C6366). In animal studies, it is commonly used for model treatment; common models include rat osteoarthritis / neuropathic pain / postoperative pain / prostatitis pain models, and canine osteoarthritis / bone cancer pain models. In cell culture, it can act on human dorsal root ganglion neurons to trigger Ca2+ influx.

Common doses in animal studies include rat intra-articular injection 0.0003%-0.03%, intrathecal injection 10-200 ng, and perineural injection 25-250 ng; canine intra-articular injection 10 μg/100 μL. Clinically, intra-articular injection of 12.5 μg in osteoarthritis patients; intrathecal 3-26 μg / epidural 0.4-25 μg in cancer pain patients; and intravesical instillation 10 nM-10 μM in overactive bladder patients. Effective therapeutic doses include 10 μg intra-articular in dogs to relieve osteoarthritis pain with a median duration of 150 days; 100 μg/kg intrathecal in rats to reverse neuropathic thermal hyperalgesia; 12.5 μg intra-articular clinically to significantly reduce WOMAC pain scores in knee osteoarthritis patients with efficacy lasting for months; 10 nM-100 nM intravesical to improve overactive bladder symptoms; and intrathecal / epidural administration to effectively relieve refractory cancer pain.

References:

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[2] Szallasi A. Resiniferatoxin: Nature's Precision Medicine to Silence TRPV1-Positive Afferents. Int J Mol Sci. 2023 Oct 10;24(20):15042. doi: 10.3390/ijms242015042. PMID: 37894723; PMCID: PMC10606200.

[3] Cui G, Wang M, Li X, Wang C, Shon K, Liu Z, Ren L, Yang X, Li X, Wu Y, Sun Z. Berberine in combination with evodiamine ameliorates gastroesophageal reflux disease through TAS2R38/TRPV1-mediated regulation of MAPK/NF-κB signaling pathways and macrophage polarization. Phytomedicine. 2024 Dec;135:156251. doi: 10.1016/j.phymed.2024.156251. Epub 2024 Nov 12. PMID: 39566409.

[4] Nehr-Majoros A, Karakai L, Payrits M, Bencze N, Kemény Á, Sétáló G Jr, Börzsei R, Hetényi C, Helyes Z, Szőke É. Cyclodextrins inhibit TRPV1 and TRPA1 activation-induced nociception via cholesterol depletion. J Lipid Res. 2025 Jul;66(7):100844. doi: 10.1016/j.jlr.2025.100844. Epub 2025 Jun 16. PMID: 40532876; PMCID: PMC12274755.

[5] Iadarola MJ, Sapio MR, Nahama A, Mannes AJ. Intraarticular resiniferatoxin, a potent TRPV1 agonist, for treatment of osteoarthritic pain. Pain Manag. 2025 Oct;15(10):659-670. doi: 10.1080/17581869.2025.2535271. Epub 2025 Aug 8. PMID: 40776673; PMCID: PMC12490358.