Tetracycline combinations inhibit neuropathic pain in mice

Tetracycline combinations inhibit neuropathic pain in mice

Dubbed “the silent epidemic” by the NIH, chronic pain is responsible for hundreds of billions of dollars in lost wages and medical expenses and an exponential increase in opioid use.

Despite the large scale of the epidemic, effective nonopioid alternatives for managing chronic pain remain scarce, hampered in part by the decades-long process of bringing new pain medications to market.

The researchers describe a platform for repositioning FDA-approved drugs that inhibit the activity of EphB1, a synaptic receptor implicated in neuropathic pain.

Using a structure-based in silico screen to identify drug targets, as well as an in vitro assay, X-ray crystallography, and an in vivo mouse model, the study demonstrates that drug cocktails of three FDA-approved tetracyclines—demeclocycline, chlortetracycline, and minocycline—can inhibit EphB1 phosphorylation in the brain, spinal cord, and dorsal root ganglion to block neuropathic pain in mice.

In addition to offering an easily applicable treatment for neuropathic pain, the platform can be expanded to identify other novel therapies that target Eph/Ephrin-mediated illnesses, according to the authors.