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

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Maiarù, M. orcid id iconORCID: https://orcid.org/0000-0003-0927-6567, Leese, C., Certo, M., Echeverria-Altuna, I., Mangione, A. S., Arsenault, J., Davletov, B. and Hunt, S. P. (2018) Selective neuronal silencing using synthetic botulinum molecules alleviates chronic pain in mice. Science Translational Medicine, 10 (450). eaar7384. ISSN 1946-6234 doi: 10.1126/scitranslmed.aar7384

Abstract/Summary

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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Item Type Article
URI https://reading-clone.eprints-hosting.org/id/eprint/90875
Identification Number/DOI 10.1126/scitranslmed.aar7384
Refereed Yes
Divisions No Reading authors. Back catalogue items
Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Publisher American Association for the Advancement of Science
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