Biography
Biography: Michael J Iadarola
Abstract
Dysfunctions of pain neural systems can lead to chronic pain conditions that are frequently resistant to treatment and can severely degrade quality of life. The ability to effectively treat pain is critically dependent on a detailed, quantitative, and comprehensive analysis of the molecular properties of nociceptive sensory neurons. These neurons occupy the beginning of the pain pathway and their cell bodies in dorsal root (DRG) or trigeminal ganglia connect the body to the central nervous system. Upon injury or pathophysiological insults such as diabetic neuropathy, they become “peripheral generators” which drive sensitization processes at higher level of the neuraxis. Important peripheral generators are DRG neurons that express the TRPV1 vanilloid-ligand-gated ion channel. These neurons transduce sensations of painful heat and inflammation, and play a fundamental role in clinical pain from cancer and arthritis. We have used the ultrapotent TRPV1 agonist resiniferatoxin (RTX) in animal and human clinical trials to produce a highly selective chemoaxotomy of pain-sensing neurons. Loss of the TRPV1-dependent peripheral generators produced a potent pain reduction in both cancer and arthritis in canine clinical pain and we are evaluating this in human cancer pain. These results prompted us to elucidate the complete transcriptome of TRPV1-expressing DRG neurons using next-generation RNA-Seq. We also performed transcriptome analysis of the non-TRPV1 neuro-glial ganglionic and selective genetic and chemical ablation. The transcriptomic data define distinct molecular signatures within a clinically important neuronal population and provide an overall framework for understanding the pain processes at the molecular level.