Resiniferatoxin for Pain Treatment: An Interventional Approach to Personalized Pain Medicine

Abstract

This review examines existing preclinical and clinical studies related to resiniferatoxin (RTX) and its potential uses in pain treatment. Like capsaicin, RTX is a vanilloid receptor (TRPV1) agonist, only more potent. This increased potency confers both quantitative and qualitative advantages in terms of drug action on the TRPV1 containing nerve terminal, which result in an increased efficacy and a long duration of action. RTX can be delivered by a central route of administration through injection into the subarachnoid space around the lumbosacral spinal cord. It can also be administered peripherally into a region of skin or deep tissue where primary afferents nerves terminate, or directly into a nerve trunk or a dorsal root ganglion. The central route is currently being evaluated as a treatment for intractable pain in patients with advanced cancer. Peripheral administration offers the possibility to treat a wide diversity of pain problems because of the ability to bring the treatment to the site of the pain (the peripheral generator). While not all pain disorders are appropriate for RTX, tailoring treatment to an individual patient's needs via a selective and local intervention that chemically targets a specific population of nerve terminals provides a new capability for pain therapy and a simplified and effective approach to personalized pain medicine.

Pain control through selective chemo-axotomy of centrally projecting TRPV1+ sensory neurons

“…The extent of the RTX lesion can be regionally delimited by manipulation of the route of administration. Intrathecal application (18,19) can encompass multiple dermatomes, whereas an intraganglionic (14) or periganglionic (20) injection can restrict the lesion to single unilateral segments. Peripheral application under the skin (21,22), adjacent to the nerve (23,24), or intra-articularly (25,26) confines the inactivation to the local nerve terminals, achieving long-term but reversible regional analgesia.…”

“…Peripheral application under the skin (21,22), adjacent to the nerve (23,24), or intra-articularly (25,26) confines the inactivation to the local nerve terminals, achieving long-term but reversible regional analgesia. These procedure-based applications can be targeted to a patient's pain problem on an individualized basis, and allow for focused pain alleviation with minimal impact on surrounding sensory nerve fibers (18).…”

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…It is noteworthy that intrathecal RTX injection was reported to provide long-lasting (several weeks) pain relief in dogs with advanced osteosarcoma, although it had no effect on the natural progression of the disease ( Fig. 19B; reviewed in Iadarola and Mannes, 2011;Iadarola and Gonnella, 2013). The treatment was well tolerated.…”

“…RTX administration, however, had no influence on disease progression. By 14 weeks, only four dogs stayed alive (Iadarola and Gonnella, 2013). The first human patient with intractable cancer pain was enrolled into the phase I RTX trials at the National Cancer Institute in October 2009 (ClinicalTrials.gov identifier NCT00804154).…”

Osteosarcomagenesis: Biology, Development, Metastasis, and Mechanisms of Pain

“…Capsaicin and other TRPV1 agonists selectively stimulate nociceptive neurons, and thus while it induces pain, it is possible to treat pain by boosting analgesic pathways [91]. In this regard the use of the TRPV1 agonist, resiniferatoxin (RTX), to block cancer pain has recently been reviewed [92]. In human cancer patients, RTX was given by intrathecal injection into the lumbar cistern, and all patients experienced substantial analgesia without signiicant side efects.…”