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.
Highlights
The sheer diversity of pain disorders and the multiplicity of locations in the body in which pain can occur, literally1876-3863/13 from the head to the toe (Morton’s neuroma) presents, if not a bewildering, certainly a complex array of possibilities for pathological pain generating mechanisms and for treatments
We examine the differences between a vanilloid antagonist and a vanilloid agonist for pain control
The main elements considered in this review are as follows: the peripheral nervous system can be targeted by RTX to produce analgesia, the local administration of RTX further enhances specificity and reduces potential side effects and local injection can be adapted to treat many different types of pain problems
Summary
The sheer diversity of pain disorders and the multiplicity of locations in the body in which pain can occur, literally. 1876-3863/13 from the head (facial nerve injury) to the toe (Morton’s neuroma) presents, if not a bewildering, certainly a complex array of possibilities for pathological pain generating mechanisms and for treatments This multiplicity and complexity makes identifying unifying principles, critical mechanisms and molecular targets for therapeutic intervention challenging propositions. The main elements considered in this review are as follows: the peripheral nervous system can be targeted by RTX to produce analgesia, the local administration of RTX further enhances specificity and reduces potential side effects and local injection can be adapted to treat many different types of pain problems This is the essence of the idea of an interventional approach to personalized pain medicine. Selective destruction of nociceptive nerve endings (e.g., with capsaicin or RTX)
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