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Substance P-botulinum mediates long-term silencing of pain pathways that can be re-instated with a second injection of the construct in mice

Maiarù, Maria, Leese, Charlotte, Silva-Hucha, Silvia, Fontana-Giusti, Sofia, Tait, Luke, Tamagnini, Francesco, Davletov, Bazbek and Hunt, Stephen P. 2024. Substance P-botulinum mediates long-term silencing of pain pathways that can be re-instated with a second injection of the construct in mice. The Journal of Pain 25 (6) , 104466. 10.1016/j.jpain.2024.01.331

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Abstract

Chronic 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Psychology
Cardiff University Brain Research Imaging Centre (CUBRIC)
Additional Information: License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Start Date: 2024-01-10
Publisher: Elsevier
ISSN: 1526-5900
Date of First Compliant Deposit: 15 January 2024
Date of Acceptance: 6 January 2024
Last Modified: 11 Jun 2024 09:42
URI: https://orca.cardiff.ac.uk/id/eprint/165493

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