Selective neuronal silencing using synthetic botulinum molecules alleviates chronic pain in mice.

Science Translational Medicine
Maria MaiarùStephen P Hunt

Abstract

Chronic pain is a widespread debilitating condition affecting millions of people worldwide. Although several pharmacological treatments for relieving chronic pain have been developed, they require frequent chronic administration and are often associated with severe adverse events, including overdose and addiction. Persistent increased sensitization of neuronal subpopulations of the peripheral and central nervous system has been recognized as a central mechanism mediating chronic pain, suggesting that inhibition of specific neuronal subpopulations might produce antinociceptive effects. We leveraged the neurotoxic properties of the botulinum toxin to specifically silence key pain-processing neurons in the spinal cords of mice. We show that a single intrathecal injection of botulinum toxin conjugates produced long-lasting pain relief in mouse models of inflammatory and neuropathic pain without toxic side effects. Our results suggest that this strategy might be a safe and effective approach for relieving chronic pain while avoiding the adverse events associated with repeated chronic drug administration.

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Citations

Aug 18, 2018·Nature Reviews. Drug Discovery·Sarah Crunkhorn
Nov 30, 2018·Expert Opinion on Emerging Drugs·Giorgio LambruPaolo Martelletti
Sep 13, 2019·Nature·Anthony King
Dec 27, 2019·The British Journal of Dermatology·B R Thomas, A Sahota
Apr 17, 2019·CNS Drugs·Kristian Agmund Haanes, Lars Edvinsson
Jan 11, 2020·Frontiers in Neuroscience·John ManionG Gregory Neely
Jan 8, 2020·International Journal of Molecular Sciences·Minhong TangJiafu Wang

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