Maiarù, M. orcid.org/0000-0003-0927-6567, Leese, C. orcid.org/0000-0002-3123-0154, Certo, M. et al. (5 more authors) (2018) Selective neuronal silencing using synthetic botulinum molecules alleviates chronic pain in mice. Science Translational Medicine, 10 (450). eaar7384. ISSN 1946-6234
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 The Authors. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Funding Information: | Funder Grant number MEDICAL RESEARCH COUNCIL MR/K022539/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 01 Aug 2018 10:21 |
Last Modified: | 01 Aug 2018 10:21 |
Published Version: | https://doi.org/10.1126/scitranslmed.aar7384 |
Status: | Published |
Publisher: | American Association for the Advancement of Science |
Refereed: | Yes |
Identification Number: | 10.1126/scitranslmed.aar7384 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:133672 |