Mangione, AS; Obara, I; Maiarú, M; Geranton, SM; Tassorelli, C; Ferrari, E; Leese, C; ... Hunt, SP; + view all Mangione, AS; Obara, I; Maiarú, M; Geranton, SM; Tassorelli, C; Ferrari, E; Leese, C; Davletov, B; Hunt, SP; - view fewer (2016) Nonparalytic botulinum molecules for the control of pain. Pain , 157 (5) pp. 1045-1055. 10.1097/j.pain.0000000000000478.

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Abstract

Local injections of botulinum toxins have been reported to be useful 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 synthesised 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 behaviours 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 as well as 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.

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