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Nonparalytic botulinum molecules for the control of pain

Lookup NU author(s): Dr Ilona Obara



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2016 International Association for the Study of Pain.Local injections of botulinum toxins have been reported to be useful not only for the treatment of peripheral neuropathic pain and migraine but also to cause long-lasting muscle paralysis, a potentially serious side effect. Recently, a botulinum A-based molecule ("BiTox") has been synthesized that retains neuronal silencing capacity without triggering muscle paralysis. In this study, we examined whether BiTox delivered peripherally was able to reduce or prevent the increased nociceptive sensitivity found in animal models of inflammatory, surgical, and neuropathic pain. Plasma extravasation and edema were also measured as well as keratinocyte proliferation. No motor deficits were seen and acute thermal and mechanical nociceptive thresholds were unimpaired by BiTox injections. We found reduced plasma extravasation and inflammatory edema as well as lower levels of keratinocyte proliferation in cutaneous tissue after local BiTox injection. However, we found no evidence that BiTox was transported to the dorsal root ganglia or dorsal horn and no deficits in formalin-elicited behaviors or capsaicin or formalin-induced c-Fos expression within the dorsal horn. In contrast, Bitox treatment strongly reduced A-nociceptor-mediated secondary mechanical hyperalgesia associated with either complete Freund's adjuvant (CFA)-induced joint inflammation or capsaicin injection and the hypersensitivity associated with spared nerve injury. These results imply that although local release of neuromodulators from C-fibers was inhibited by BiTox injection, C-nociceptive signaling function was not impaired. Taken together with recent clinical data the results suggest that BiTox should be considered for treatment of pain conditions in which A-nociceptors are thought to play a significant role.

Publication metadata

Author(s): Mangione AS, Obara I, Maiaru M, Geranton SM, Tassorelli C, Ferrari E, Leese C, Davletov B, Hunt SP

Publication type: Article

Publication status: Published

Journal: Pain

Year: 2016

Volume: 157

Issue: 5

Pages: 1045-1055

Print publication date: 01/05/2016

Acceptance date: 22/12/2015

Date deposited: 01/09/2017

ISSN (print): 0304-3959

ISSN (electronic): 1872-6623

Publisher: Lippincott Williams and Wilkins


DOI: 10.1097/j.pain.0000000000000478

PubMed id: 26761389


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