Pain management is important for a variety of disorders including inflammatory hyperalgesia, osteoarthritis, and terminal cancer. Pain treatment requires balancing the elimination of sensory pain with the maintenance of effective proprioceptive, motor, and cognitive neuronal function. In the May 3 issue of The Journal of Clinical Investigation, Michael Iadarola and colleagues from the National Institute of Dental and Craniofacial Research, targeted vanilloid receptors, which are enriched in pain-sensing primary afferent neurons, by using resiniferatoxin (RTX). RTX is a potent vanilloid receptor 1 (TRPV1) agonist that leads to cellular cytotoxicity through excessive calcium influx. The researchers demonstrated, immunohistochemically, that local administration of RTX selectively deleted TRPV1-positive neurons. They then showed, using assays for analgesic activity in rat and dog models, that pain sensation decreased without a concomitant motor impairment or induction of other sensory neuropathies. Finally, the potential for this form of pain treatment in humans was emphasized by live cell-imaging of human dorsal root ganglia (DRG) in culture using Fluo-4. As previously shown in rats, only a portion of the human DRG neurons were found to be activated by RTX, indicating the likelihood for similar mechanisms and alleviation of pain when used clinically.
TITLE: Deletion of vanilloid receptor 1_expressing primary afferent neurons
for pain control
Michael J. Iadarola
National Institute of Dental and Craniofacial Research, Bethesda, Maryland. USA.
View the PDF of this article at: http://www.jci.org/cgi/content/full/113/9/1344