This review examines existing preclinical and clinical studies related to resiniferatoxin (RTX) and its potential uses in pain treatment. the lumbosacral spinal cord. It can also be administered peripherally into a region of skin or deep tissue where main afferents nerves terminate or directly into a nerve trunk or a dorsal root ganglion. The central route is currently Ceramide 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 Ceramide 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 Ceramide targets a specific population of nerve terminals provides a new capability for pain therapy and a simplified and effective approach to personalized pain medicine. nociceptive sensitivity: complete loss of pain sensitivity can be life threatening. Even the complete loss of one modality (e.g. hot thermal pain) is not desirable for long term care because it can negatively affect ADL . One advantage of RTX in comparison to local anesthetics is that it is selective for the nociceptive population of primary afferent fibers and indeed a subpopulation of nociceptive afferents [35-37]. The sensations of mechanical pinch and pressure are largely intact following RTX administration as are sensations of vibration and cold temperature. Furthermore proprioceptive sensations necessary for locomotion are unaffected. Rats injected with RTX intrathecally can walk on a Rotorod in a similar fashion as vehicle injected rats and for a similar duration . We also see no motor impairment in dogs injected intrathecally with RTX by either the intracisternal or lumbar puncture routes Mouse monoclonal to CRTC2 . Data from multiple studies support the conclusion that the selectivity afforded by RTX spares motor axons and other sensory inputs which is a significant factor when assessing safety ADL and quality of life. These are important considerations for the intrathecal route Ceramide because it affects many dorsal roots at once  but they are equally important when considering local administration paradigms. For example the sparing of mechanoreceptors is critically important for corneal applications where the blink reflex must remain intact  Similarly for joint injections feedback from specialized muscle spindle and Golgi tendon organ proprioceptors is an essential component of muscular coordination. Sparing of mechano-responsive nociceptive axons and nerve endings may also help protect against damage to the joint from inappropriate use. All of these considerations obviously apply to chronic pain conditions where long-term analgesia and side effects are important elements. RTX can also be used for acute conditions where nerve terminals are damaged or will be damaged (e.g. a proposed elective surgery). Two potential examples are the use of RTX to control burn or post-operative pain respectively. In the former case RTX application would occur after the injury. In the latter case RTX would be applied in a preemptive fashion. In both cases the nerve terminals in the pain zone are the targets although the formulation of the drug and the means of administration may be different. In summary pain treatment with RTX can encompass a wide variety of acute and chronic pain problems with two provisos: firstly the drug must contact the TRPV1 molecule as it resides in the nerve terminals axons or neuronal cell bodies of TRPV1-expessing sensory ganglionic neurons. Secondly the injection site must coincide with the neurons causing the pain. Thus issues of etiology pain localization accessibility to injection duration of exposure to RTX and spread of the drug from the site of injection are all aspects of a personalized interventional approach that will govern optimal therapeutic outcome. Differences Between Peripheral and Intrathecal Routes of Administration The above introduction suggests that RTX can be a versatile agent for treatment of a wide variety of pain problems. Two main routes of administration peripheral and intrathecal provide an appropriate framework Ceramide for conceptualizing how to use this compound and are summarized in Table 2A and B. The main feature of the.