The figure depicts two drug receptor sites with the molecular structure of the Nav1.7 channel and tamoxifen attenuation of nociceptor action potentials responsible for the transmission of aberrant pain signals. Author: Northwestern University

According to a Northwestern Medicine study published in Cell reports.

Paul Dean, PhD, associate professor of pharmacology, was the study’s senior author.

Nociceptor neurons transmit pain signals to the brain using electrical currents created by voltage sodium channels; when overactive, these channels are commonly seen in cases of osteoarthritis and other aberrant pain conditions.

Targeting sodium channels to improve pain management in osteoarthritis is being considered as a potential therapeutic strategy. Previous work from the DeCaen lab demonstrated that a metabolite of tamoxifen, an estrogen receptor modulator, binds to the intracellular outlet of the channel, highlighting its therapeutic potential.

Despite the obvious need, efforts to develop new sodium channel blockers for actual therapy have been challenging, according to DeCaen.

“Variation of Tamoxifen Metabolites Commonly Used for Treatment breast cancerpresents an alternative strategy that can bypass the first stage clinical trials” – said the Dean.

In the current study, DeCaen’s team administered a tamoxifen metabolite to mice that had been genetically modified to develop osteoarthritis symptoms. They found that the drug binds to two intracellular receptor sites in sodium channels, blocking ion entry through a bind-and-plug mechanism and inhibiting sodium channels in inflamed, overactivated nociceptor neurons responsible for osteoarthritis pain.

“To our knowledge, the clinical efficacy of tamoxifen metabolites for the treatment of osteoarthritis pain has not been tested. However, many years of oncology clinical data greatly reduces the risk of their use, which could lower the overall cost of developing their use for the treatment of osteoarthritis pain,” said DeCaen.

New insights into sodium channel structure

Additional information:
Megan M. McCollum et al. Targeting the Tamoxifen Sodium Channel Receptor to Block Osteoarthritis Pain, Cell reports (2022). DOI: 10.1016/j.celrep.2022.111248

Citation: Targeting Ion Channels to Combat Osteoarthritis Pain (2022, October 5) Retrieved October 5, 2022, from

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