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

Maiarù, M; Leese, C; Certo, M; Echeverria-Altuna, I; Mangione, AS; Arsenault, J; Davletov, B; (2018) Selective neuronal silencing using synthetic botulinum molecules alleviates chronic pain in mice. Science Translational Medicine , 10 (450) , Article eaar7384. 10.1126/scitranslmed.aar7384. Green open access

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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.

Type: Article
Title: Selective neuronal silencing using synthetic botulinum molecules alleviates chronic pain in mice
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/scitranslmed.aar7384
Publisher version: http://dx.doi.org/10.1126/scitranslmed.aar7384
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10053955
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