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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, M., Leese, C., Silva-Hucha, S., Fontana-Giusti, S., Tait, L., Tamagnini, F. ORCID: https://orcid.org/0000-0002-8741-5094, Davletov, B. and Hunt, S. 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. ISSN 1526-5900

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To link to this item DOI: 10.1016/j.jpain.2024.01.331

Abstract/Summary

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
Refereed:Yes
Divisions:Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
ID Code:114891
Uncontrolled Keywords:Neuronal silencing, Analgesia, Pain, Botulinum-based construct
Publisher:Elsevier

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