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Sci Transl Med. 2018 Jul 18;10(450). pii: eaar7384. doi: 10.1126/scitranslmed.aar7384.

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

Author information

1
Cell and Developmental Biology, Medawar Building (G13), Gower Street, London WC1E 6BT, UK.
2
Department of Biomedical Science, University of Sheffield, South Yorkshire S10 2TN, UK.
3
Peter Gilgan Centre for Research and Learning, Neuroscience and Mental Health Department, Hospital for Sick Children, Toronto, M5G 0A4 Ontario, Canada.
4
Department of Biomedical Science, University of Sheffield, South Yorkshire S10 2TN, UK. b.davletov@sheffield.ac.uk hunt@ucl.ac.uk.
5
Cell and Developmental Biology, Medawar Building (G13), Gower Street, London WC1E 6BT, UK. b.davletov@sheffield.ac.uk hunt@ucl.ac.uk.

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.

PMID:
30021888
DOI:
10.1126/scitranslmed.aar7384
[Indexed for MEDLINE]

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