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Botulinum toxin compound may be effective against chronic pain

Researchers have found a modified form of botulinum toxin -- different from the version used to treat facial fine lines and wrinkles -- gave long-lasting pain relief without adverse side effects in mice.

The botulinum molecule, which is sold under the brand name Botox, was deconstructed and reassembled with an opioid called dermorphin to make Derm-BOT, according to researchers at University College London, University of Sheffield in England and the Hospital for Sick Children, Toronto. The findings, published Wednesday in the journal Science Translational Medicine, show how it can successfully targeted and silenced pain signals from neurons in mice's spinal cords.


"It doesn't affect muscles like the botulinum toxin used to reduce wrinkles but it does block nerve pain for up to four months without affecting normal pain responses," co-corresponding author Dr. Steve Hunt, a professor in cell and developmental biology at UCL, said in a press release. "It really could revolutionize how chronic pain is treated if we can translate it into clinic, removing the need for daily opioid intake."

In the spinal cord, key neurons directly "sense" pain and send this information to the brain.

With opioids, the body builds up a tolerance to repeated use -- and can also increase the body's sensitivity to pain. Additionally, opioids activate brain reward regions that can facilitate misuse and addiction to the drugs.

"Injected into the spine, Derm-BOT relieves chronic pain -- such as that caused by nerve damage -- and avoids the adverse events of tolerance and addiction often associated with repeated opioid drug use," Hunt said.

Previously, tiny amounts of toxic substances, such as "substance P-saporin," were injected into the spines of rats and dogs. But the methods reliance on an analogue of ricin is difficult to manufacture to clinical standards and it can irreversibly kill nerve cells.

Derm-BOT, however, does not kill neurons and is safe to manufacture, the researchers said.

"We needed to find the best pain targeting molecular parts to direct the botulinum silencing 'warhead' to the pain-controlling system in the spine," said co-corresponding author Dr. Bazbek Davletov, of the Department of Biomedical Science at the University of Sheffield. "For this, we developed a molecular Lego system which allows us to link the botulinum 'warhead' to a navigation molecule, in this case, the strong opioid called dermorphin."

Over five years, 200 mice with early stages of human inflammatory and neuropathic pain were treated with a single injection of one of two botulinum-conjugated molecules -- Derm-BOT or SP-BOT -- or morphine.

The researchers found the single injection reduced "mechanical hypersensitivity" to the same level as morphine.

"Both SP-BOT and Derm-BOT have a long-lasting effect in both inflammatory and neuropathic pain model, successfully silencing neurons without cell death," said lead author Dr. Maria Maiaru, a professor in cell and developmental biology at UCL. "We were impressed to see that one tiny injection was enough to stop chronic pain caused by inflammation and nerve damage for at least a month."

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