• Maria Maiarù, Charlotte Leese, Silvia Silva-Hucha, Sofia Fontana-Giusti, Luke Tait, Francesco Tamagnini, Bazbek Davletov, and Stephen P Hunt.
• Department of Pharmacology, School of Pharmacy, University of Reading; Room 109, Hopkins Building, Whiteknights Campus, Reading RG6 6UB, United Kingdom.
• J Pain. 2024 Jun 1; 25 (6): 104466104466.

AbstractChronic pain presents an enormous personal and economic burden and there is an urgent need for effective treatments. In a mouse model of chronic neuropathic pain, selective silencing of key neurons in spinal pain signalling networks with botulinum constructs resulted in a reduction of pain behaviours associated with the peripheral nerve. However, to establish clinical relevance it was important to know how long this silencing period lasted. Now, we show that neuronal silencing and the concomitant reduction of neuropathic mechanical and thermal hypersensitivity lasts for up to 120d following a single injection of botulinum construct. Crucially, we show that silencing and analgesia can then be reinstated with a second injection of the botulinum conjugate. Here we demonstrate that single doses of botulinum-toxin conjugates are a powerful new way of providing long-term neuronal silencing and pain relief. PERSPECTIVE: This research demonstrates that botulinum-toxin conjugates are a powerful new way of providing long-term neuronal silencing without toxicity following a single injection of the conjugate and have the potential for repeated dosing when silencing reverses.Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.

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