Anti-Inflammatory Effects of BoNT/A Against Complete Freund’s Adjuvant-Induced Arthritis Pain in Rats: Transcriptome Analysis

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.

Botulinum toxin type A ameliorates rat dorsal root ganglia neuron pyroptosis in postherpetic neuralgia by upregulating cathelicidin antimicrobial peptide to inhibit neutrophil elastase

“…BoNT/A treatment (10, 20, and 30 U/kg) reversed RTX‐induced decrease of rat PWL (Figure 1a, p < .05). The expression of cl‐SNAP‐25 has been identified as a marker for BoNT/A (X. Li, Ye, et al., 2021). IF assay showed that cl‐SNAP‐25 was obviously detected in RTX‐induced rat DRG after BoNT/A injection (20 and 30 U/kg) (Figure 1b,c, p < .001).…”

“…CAMP has been linked to BoNT/A‐mediated pain relief in Complete Freund's Adjuvant‐stimulated arthritis pain (X. Li, Ye, et al., 2021). Vitamin D, an inducer of CAMP, is known to improve the efficacy of antiviral therapy on PHN (Lin et al., 2019).…”

“…The upregulation of cathelicidin antimicrobial peptide (CAMP) has been implicated in BoNT/A‐mediated anti‐inflammatory activities against arthritis pain (X. Li, Ye, et al., 2021). LL‐37, the active form of CAMP, is a human peptide cleaved from hCAP18 (White, 2022).…”

Transcriptome analysis during axillary bud growth in chrysanthemum (chrysanthemum×morifolium)

“…Total amounts and integrity of RNA were assessed using the RNA Nano 6000 Assay Kit of the Bioanalyzer 2100 system (Agilent Technologies, Santa Clara, CA, USA). The test method is the same as previously described in Li et al (2021) . mRNA was purified using poly-T and oligo-attached magnetic beads.…”

Degenerative and regenerative peripheral processes are associated with persistent painful chemotherapy-induced neuropathies in males and females

“…Chronic pain conditions can develop through several phases: initiation of pain, pain maintenance, and finally, either resolution or persistency of hypersensitivity/pain. Bulk RNA-sequencing (RNA-seq) experiments show that pain conditions trigger substantial gene expression plasticity in nociceptive pathway tissues, including the DRG and spinal cord(Cao et al, 2019; North et al, 2019; Tang et al, 2020; Guo et al, 2021; Li et al, 2021a; Li et al, 2021b; Doty et al, 2022; Xu et al, 2022). Despite this progress, there are still several gaps in knowledge.…”