ROCHESTER, Minn. -- Chronic pain severely limits patients' quality of life and is among the cost drivers in U.S. health care. Patients can suffer pain without an apparent cause and often fail to respond to available treatments. Mayo Clinic researchers and collaborators now report that chronic pain may be caused by the inadvertent reprogramming of more than 2,000 genes in the peripheral nervous system. The research findings appear in the current issue of the journal Genome Research.
The research might ultimately lead to "transcription therapy" the researchers speculate, which would employ drugs that kill pain by correcting the activity of specific genes.
The researchers focused on nerve cells suspected to be involved in pain: dorsal root ganglion neurons of the peripheral nervous system in rodent models. They performed high-throughput sequencing of hundreds of millions of mRNA molecules, the messengers of gene activity.
Powerful computer science was required to sort through the many pieces of information (50 base-pair long mRNA sequence "reads") assembling the complicated genomic puzzle. The resulting picture revealed a number of surprises, among them 10,464 novel exons (sections of the genome involved in creating proteins) and some 400 gene candidates described for the first time in the study. Furthermore, detailed building plans for thousands of spliced mRNA were mapped.
"Using this new approach offers greater sensitivity, dynamic range and more efficient unbiased genetic mapping compared to the previous microarray-based methods and may be an efficient new approach to a wide array of problems in neuroscience research," says Andreas Beutler, M.D., Mayo Clinic oncologist and corresponding author on the study.
Chronic pain affects 50 million Americans and costs $100 billion in health costs, lost work time and other economic impacts, according to the National Institutes of Health.
Others involved in the study were Michaela Banck, M.D., and Ronny Amberg, both of Mayo Clinic; Paul Hammer, Gabriele Petznick, and Peter Beyerlein, Ph.D. all of the University of Applied Sciences, Wildau, Germany; Cheng Wang, M.D., Mount Sinai School of Medicine; and Shujun Luo, Ph.D., Irina Khrebtukova, Ph.D., and Gary P. Schroth, Ph.D. all of Illumina Inc., Hayward, Calif.
The study was supported by the Richard M. Schulze Family Foundation and the National Institute of Neurological Disorders and Stroke.
About Mayo Clinic
For more than 100 years, millions of people from all walks of life have found answers at Mayo Clinic. These patients tell us they leave Mayo Clinic with peace of mind knowing they received care from the world's leading experts. Mayo Clinic is the first and largest integrated, not-for-profit group practice in the world. At Mayo Clinic, a team of specialists is assembled to take the time to listen, understand and care for patients' health issues and concerns. These teams draw from more than 3,700 physicians and scientists and 50,100 allied staff that work at Mayo Clinic's campuses in Minnesota, Florida, and Arizona; and community-based providers in more than 70 locations in southern Minnesota, western Wisconsin and northeast Iowa. These locations treat more than half a million people each year. To best serve patients, Mayo Clinic works with many insurance companies, does not require a physician referral in most cases and is an in-network provider for millions of people. To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. For information about research and education, visit www.mayo.edu. MayoClinic.com (www.mayoclinic.com) is available as a resource for your general health information.
Journal
Genome Research