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- Title
Botulinum toxin type A ameliorates rat dorsal root ganglia neuron pyroptosis in postherpetic neuralgia by upregulating cathelicidin antimicrobial peptide to inhibit neutrophil elastase.
- Authors
Wan, Quan
- Abstract
Botulinum toxin type A (BoNT/A) has exhibited efficacy in postherpetic neuralgia (PHN) treatment, and this study aims to uncover its underlying mechanisms. Resiniferatoxin (RTX)‐induced PHN rats were given BoNT/A. Rat postoperative pain behaviors were assessed by Von Frey test. Cleaved‐synaptosomal protein 25 kDa (cl‐SNAP‐25) or cathelicidin antimicrobial peptide (CAMP) expression in rat dorsal root ganglia (DRG) was detected by immunofluorescence or immunohistochemistry. Healthy rat‐derived DRG neurons were transfected, incubated with lipopolysaccharides (LPS)/adenosine 5′‐triphosphate (ATP) to stimulate pyroptosis and treated with BoNT/A. The CCK‐8, Western blot, ELISA, and qRT‐PCR were used to assess the viability, levels of pyroptosis‐related proteins proinflammatory cytokine levels, as well as CAMP and ELANE mRNA levels. BoNT/A (30 U/kg) promoted cl‐SNAP‐25 expression in rat DRG and reversed RTX‐induced decrease of rat paw withdrawal thresholds and CAMP expression and increase of pyroptosis‐associated protein and inflammatory factor expression in rat DRG. CAMP interacted with ELANE in rat DRG neurons. BoNT/A attenuated LPS/ATP‐stimulated inhibition of viability and CAMP expression and upregulation of inflammatory mediators, pyroptosis‐related proteins, and ELANE expression in rat DRG neurons, which was counteracted by CAMP silencing. However, ELANE knockdown offset the effect of CAMP silencing in LPS/ATP/BoNT/A‐treated rat DRG neurons. On the whole, BoNT/A alleviates rat DRG neuron pyroptosis during PHN by upregulating CAMP to inhibit ELANE.
- Subjects
BOTULINUM toxin; BOTULINUM A toxins; DORSAL root ganglia; ANTIMICROBIAL peptides; LEUCOCYTE elastase; POSTHERPETIC neuralgia; PYROPTOSIS
- Publication
Chemical Biology & Drug Design, 2024, Vol 103, Issue 1, p1
- ISSN
1747-0277
- Publication type
Article
- DOI
10.1111/cbdd.14406