Arthritis and Chronic Pain Research Institute Understanding the Pain Mechanism

Need

Chronic pain is a condition that afflicts some 86 million Americans, in forms ranging from low-level discomfort to disabling agony. Chronic pain presents a major challenge to health professionals, since by its very nature it is a problem that will not go away and all too often responds with only mixed success to current modes of treatment.

Solution

The mission of the Arthritis & Chronic Pain Research Institute is to find solutions for those who suffer from chronic pain. By providing financial support for biomedical research on understanding chronic pain, its causes, and possible therapeutics, we hope to make a difference in the lives of pain sufferers and their loved ones.

Impact

One research project funded in part by the Institute involves the development of new synthetic compounds to understand the pain mechanism. The approach involves using peptide neurotoxins discovered from venomous cone snails as templates for designing synthetic molecules that selectively modulate pain through nicotinic receptors. There are many different types of nicotinic receptors in the central and peripheral nervous systems that perform different roles, including pain transmission. As such, specifically blocking these subtypes of nicotinic receptors may help alleviate pain in people that do not respond well to traditional medications such as opiates. However, a major problem for researchers lies in identifying the specific role that each subtype of nicotinic receptor plays in the nervous system. One particular class of cone snail toxins, the α-conotoxins, can distinguish between different subtypes of nicotinic receptors. The scientist then uses the unique molecular structure of α-conotoxins as templates in the design of synthetic combinatorial libraries that accelerate the discovery of selective and potent new nicotinic receptor ligands. Conducted in collaboration with the University of Copenhagen, this research has resulted in the development of new selective compounds which have been shown to be 15 times more potent than the native conotoxin and are being further studied to improve the understanding of the interaction at the molecular level of α-conotoxins and nicotinic receptors. This research project has exciting potential for unraveling the function of these receptors with profound implications in the development of more effective analgesics.