Funded Projects

The NIH’s HEAL Initiative aims to support collaboration between clinical research experts in academia and industry to accelerate the development of highly efficacious, nonaddictive analgesics for well-defined chronic pain syndromes. The University of Rochester (UR), and its leadership for the UR Hub and Spokes within Early Phase Pain Investigation Clinical Network (EPPIC-Net), will recruit subjects with a broad range of pain conditions, with a focus on leveraging clinical trial infrastructure to support patient recruitment and retention, timely and accurate data entry, and regulatory documentation, as well as recruit additional Spoke sites through a national network of analgesic researchers.

Dorsal root ganglion (DRG) neuronal hyperexcitability is central to the pathology of neuropathic pain and is a target for local anesthetics, even though the efficacy of local anesthetic patches has been mixed. The coordinated movement of ion channels, especially voltage-dependent sodium channels, from intracellular pools to the sites of nerve injury has been suggested to be an underlying cause of electrogenesis and ectopic firing in neuropathic pain conditions. Recent studies identified Magi1 as a scaffold protein responsible for sodium channel targeting and membrane stabilization in DRG neurons. This project will determine whether reducing the expression Magi1 could disrupt intracellular trafficking of sodium channels in DRG neurons under neuropathic injury conditions, and could therefore serve as a potential therapeutic target for neuropathic pain.

Chronic pain is a major healthcare burden. However, the types and underlying mechanisms of pain vary greatly, as do patient responses to currently available pain medications. Inflammation in the nervous system (neuroinflammation) is involved in several types of pain, and targeting key molecules involved in neuroinflammation is therefore a promising treatment approach. The chemokine receptor system, a complex network of more than 20 different receptors and more than 80 molecules that bind to these receptors, has a central role in neuroinflammation. Researchers do not yet fully understand the functioning of this network and how specific receptors vary in different chronic pain conditions. Therefore, this project aims to further characterize the expression of one specific receptor, using samples collected from participants in clinical trials evaluating a compound that interferes with the receptor’s function. This information should allow researchers to classify pain patients and identify those most likely to benefit from a treatment with compounds targeting the receptor.