Abstract
For the past two decades, botulinum neurotoxin A (BoNT/A) has been described as a strong candidate in the treatment of pain. With the production of modified toxins and the potential new applications at the visceral level, there is a real need for tools allowing the assessment of these compounds. In this study, we evaluated the jejunal mesenteric afferent nerve assay to investigate BoNT/A effects on visceral nociception. This ex vivo model allowed the continuous recording of neuronal activity in response to various stimuli. BoNT/A was applied intraluminally during three successive distensions, and the jejunum was distended every 15 min for 3 h. Finally, samples were exposed to external capsaicin. BoNT/A intoxication was validated at the molecular level with the presence of cleaved synaptosomal-associated protein of 25 (SNAP25) in nerve terminals in the mucosa and musculosa layers 3 h after treatment. BoNT/A had a progressive inhibitory effect on multiunit discharge frequency induced by jejunal distension, with a significant decrease from 1 h after application without change in jejunal compliance. The capsaicin-induced discharge was also affected by the toxin. This assay allowed the description of an inhibitory effect of BoNT/A on afferent nerve activity in response to distension and capsaicin, suggesting BoNT/A could alleviate visceral nociception.
Highlights
Famous in the field of aesthetics, botulinum neurotoxin A (BoNT/A), produced by the bacterium Clostridium botulinum, is a therapeutic solution in the treatment of various pathologies [1]
The main objectives of this study were to evaluate whether the jejunum mesenteric nerve assay could be an effective tool to assess the effects of toxins on visceral nociception, and to measure the impact of an intraluminal perfusion of a controlled quantity of BoNT/A on mesenteric afferent nerve activity in response to nociceptive jejunal distension and capsaicin serosal exposure
The mouse jejunal mesenteric nerve preparation was sensitive to BoNT/A at the afferent level in our study
Summary
Famous in the field of aesthetics, botulinum neurotoxin A (BoNT/A), produced by the bacterium Clostridium botulinum, is a therapeutic solution in the treatment of various pathologies [1]. After binding onto a synaptic vesicle 2 (SV2) receptor and undergoing cellular internalization, BoNT/A cleaves SNAP25 (Synaptosomal-Associated Protein, 25 kDa) [2]. This membranal t-SNARE protein (Target Soluble NSF (N-ethylmaleimide-sensitive factor) Attachment Protein Receptor), as is characteristic of the other SNARE family members, plays an important role in the membrane fusion mechanism [3]. Cleavage of this protein causes the inhibition of neurotransmitter exocytosis [4]. Injections of BoNT/A are used to treat hyperhidrosis and sialorrhea, by preventing the hyperstimulation of eccrine sweat and salivary glands, respectively [1,10–12]
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