U. BUFFALO (US) — There may be a way to dial down pain, without the side effects of drugs, by interrupting a process that makes certain nerve cells sensitive to inflammation.
Inflammatory pain can result from penetration wounds, burns, extreme cold, fractures, arthritis, autoimmune conditions, excessive stretching, infections, and vasoconstriction.
“There are efficacious treatments for inflammatory pain, such as corticosteroids and non-steroidal anti-inflammatory drugs,” says Arin Bhattacharjee, assistant professor of pharmacology and toxicology at the University at Buffalo, “but the adverse side effects associated with these drugs limit their long-term use and compromise patient compliance. As a result, there is a great need to understand the cellular processes involved in inflammatory pain to create less toxic, less addictive, analgesic drugs.”
Known as nociceptors, these pain-receptive nerve cells relay information to the central nervous system, indicating the location, nature, and intensity of the ensuing pain. Nociceptors are sensitized during inflammation, their ionic properties are altered, and their firing characteristics changes. This sensitization causes a state of “hyperalgesia,” or increased sensitivity to pain.
“Merely touching the inflamed area can be very painful,” says Bhattacharjee, senior author of the study reported in the Journal of Neuroscience. “The ionic mechanisms that are chiefly responsible for this inflammatory-mediated change in nociceptive firing had not been clearly identified.
“We were able to demonstrate that a certain class of potassium channels is removed from the surface of nociceptive cells during inflammatory signaling. The removal of these ion channels is linked to the hypersensitivity of these nerve cells. We demonstrated that reducing the expression of these channels by gene interference techniques produced a similar nociceptor hyperexcitability. ”
Bhattacharjee says his team plans to extend their ion channel “trafficking” studies to in vivo models, using peptide inhibitors to try to prevent the removal of the potassium channels from the surface of nociceptors during inflammation.
“We expect to show that maintaining these channels at the surface during inflammation will be effective for pain relief. Successful completion of our studies will provide the impetus for direct human clinical trials.”
The study was supported by funding from the American Diabetes Association and the John R. Oishei Foundation.
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