Gene therapy for chronic neuropathic pain

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gmccormack
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Gene therapy for chronic neuropathic pain

Post by gmccormack »

I understand this is not a chronic pain forum but more specifically a CPPS forum, but I found this article in Anasthesiology News July issue interesting and pertinent since it focuses on potential new "transciption" treatments for neuropathic pain, pain that is almost certainly invloved in CPPS.

Widespread Changes in Gene Expression Linked to Chronic Pain

David C. Holzman

Chronic pain involves reprogramming of more than 2,000 genes within several classes of cells making up the peripheral nervous system, according to an international team of researchers. The team used a new technique to map these changes in gene expression in an animal model.
“We discovered an order of magnitude more gene expression changes than were expected based on previous microarray studies performed on [dorsal root ganglion] in similar rat pain models,” the researchers wrote. “One in five genes, including previously unmapped genes with novel candidate neural regulator roles, were significantly altered, some by as much as 100-fold, in animals with neuropathic pain,” according to the report.

Roughly 400 gene candidates for pain were described for the first time in the study. The team was led by Andreas Beutler, MD, senior associate consultant in the Department of Anesthesiology at Mayo Clinic, in Rochester, Minn.

“Profound alterations in gene expression occur in the dorsal root ganglion, the key peripheral nervous system region for transmitting sensory information from the body to the spinal cord,” said Michael J. Iadarola, PhD, chief of the Neurobiology and Pain Therapeutics Section at the National Institute of Dental and Craniofacial Research. Dr. Iadarola was not involved in the research, but characterized it as “excellent.”

The research points the way toward a better understanding of chronic pain, Dr. Iadarola said. “Eventually, the findings can be incorporated into current protocols to analyze the genetic differences in pain sensitivity and susceptibility to complex persistent pain problems, such as fibromyalgia.”

Dr. Beutler speculated that the research might ultimately lead to “transcription therapy,” which would use certain drugs to alleviate pain by correcting the activity of specific aberrantly expressed genes. The National Institutes of Health estimates that 50 million Americans—nearly one out of six people in the country—suffer from chronic pain, a number that Dr. Beutler said was “on the high side.” Those who suffer from pain with neuropathic characteristics—the disease state modeled most closely in this experiment—represent a “substantial minority” of chronic pain sufferers, he said.

Dr. Beutler’s group used a new technique to characterize messenger RNA in the dorsal root ganglion neurons of the peripheral nervous systems of the rodent models.

The technique also used an algorithm that prevented bias by performing the mapping without reference to previous maps.

The investigators sequenced nucleic acid libraries from the L4 dorsal root ganglion tissue of eight rats—four that underwent ligation of the L5 spinal nerve and four that served as controls. Two sets of two treatment-arm rats and two controls were sacrificed at two weeks and two months post-ligation, respectively. The differences in gene expression between treatment-arm and control rats were fully apparent at two weeks. Among the rats with chronic pain, expression was elevated in 1,289 (12.4%) of known genes, and diminished in 721 (7%). This pattern was almost unchanged at two months.

The research appeared in Genome Research (2010;20:847-860).
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