Abstract
Arthritis is the most common cause to lead to chronic pain. Botulinum toxin type A (BoNT/A) has been widely used to treat chronic pain. In our previous study, we confirmed the anti-inflammatory and antinociceptive effects of BoNT/A in the Complete Freund’s Adjuvant (CFA)-induced arthritis model, but the underlying anti-inflammatory mechanism was not fully elucidated. The purpose of this study was to investigate the anti-inflammatory effects and mechanisms of BoNT/A on arthritis using transcriptomic analysis. The BoNT/A was injected into the rat ankle joint on day 21 after CFA injection. The von Frey and hot plate tests were applied to assess the pain-related behaviors at different time points. Five days after BoNT/A treatment, gene expression profiling in dorsal root ganglion (DRG) was performed using RNA sequencing (RNA-seq). The differentially expressed genes (DEGs) were analyzed by various tools. The mechanical allodynia and thermal hyperalgesia were significantly reversed after BoNT/A injection. RNA-seq revealed 97 DEGs between the CFA group and Sham group; these DEGs were enriched inflammatory response, IL-17 signaling pathway, etc. There are 71 DEGs between the CFA+BoNT/A group and the CFA group; these DEGs related to response to peptide, PI3K-Akt signaling pathway, ECM–receptor interactions, etc. Three key genes were significantly decreased after CFA-induced arthritis pain, while BoNT/A increased the expression of these genes. The identification of S100A9, S100A8, and MMP8 genes can provide new therapeutic targets for arthritis pain and affect the signaling pathway to play an anti-inflammatory role after the treatment of BoNT/A.
Highlights
Arthritis is a progressive disease, characterized by chronic pain, joint destruction, and decreased patient function (Bergman, 2006)
The expression of cl-SNAP-25 in dorsal root ganglion (DRG) was analyzed to determine whether retrograde transport of Botulinum toxin type A (BoNT/A) could partially explain the observed effect of anti-inflammatory pain
The results indicated that the mechanism of the anti-inflammatory effect of botulinum toxin (BoNT)/A against Complete Freund’s Adjuvant (CFA)-induced arthritis pain involves the reactions to lipopolysaccharides and peptides (Figures 5A,B) and their related signaling pathways such as PI3K-Akt signaling pathway and IL-17 signaling pathway (Figure 5C)
Summary
Arthritis is a progressive disease, characterized by chronic pain, joint destruction, and decreased patient function (Bergman, 2006). Patients with arthritis often suffer from chronic pain leading to severe disabilities and a major burden for individuals and society (Walsh et al, 2015). Chronic pain has a significantly negative impact on quality of life, and this effect increases with the duration of pain. Approaches traditionally used for refractory arthritis pain including medication, intra-articular treatments, topical treatments, and physical treatments had limited efficacy and were at risk of toxicity (Singh, 2013). It is important to explore more effective therapeutic options
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