Abstract
BackgroundBotulinum toxin type A (BTX-A) was considered to be a new potential drug for neuropathic pain (NP) treatment.ResultsIn vivo, BTX-A attenuated chronic compression injury (CCI)-induced pain in rats, and reduced production of pro-inflammatory factors. The inhibition of BTX-A to expression and phosphorylation of SNAP23 were partly reversed by TLR2/MyD88 upregulation. In LPS-stimulated microglia, we also found that BTX-A suppressed TLR2, MyD88, p-SNAP23 and SNAP23 expression, and reduced pro-inflammatory factors secretion. Upregulation of TLR2 and MyD88 recued the inhibition of BTX-A to LPS-induced activation of SNAP23. Then, we demonstrated that BTX-A reduced expression of SNAP23 through inhibition of IKKα/β phosphorylation. Besides, the inhibition of BTX-A to LPS-induced upregulation of SNAP23 can be reversed by proteasome inhibitor. NEDD4, an E3 ubiquitin ligase, was proved to be bind with SNAP23. BTX-A reduced expression of SNAP23 via facilitating ubiquitin-mediated degradation of SNAP23.ConclusionOverall, our data demonstrated that BTX-A attenuated NP via reducing the secretion of pro-inflammatory factors from microglia by inhibition of TLR2/MyD88 signaling. BTX-A downregulated expression of SNAP23 via reducing phosphorylation of IKKα/β, and enhancing ubiquitination of SNAP23 by suppressing TLR2/MyD88 signaling.
Highlights
Botulinum toxin type A (BTX-A) was considered to be a new potential drug for neuropathic pain (NP) treatment
We proved that BTX-A attenuated chronic compression injury (CCI)-induced neuropathic pain in rats, reduced releasing of pro-inflammatory factors from activated microglia and expression of Synaptosome associated protein 23 (SNAP23) through inhibition toll-like receptor 2 (TLR2) expression
BTX‐A inhibited TLR2 and MyD88 expression in NP rats It was reported that the expression of TLR2 in LPS-stimulated microglia was proved to be affect by BTX-A, while BTX-A has no effect on the expression of TLR4 [9]
Summary
Botulinum toxin type A (BTX-A) was considered to be a new potential drug for neuropathic pain (NP) treatment. Neuropathic pain (NP) is a pain syndrome characterized by the spontaneously intermittent or ongoing burning pain, allodynia and hyperalgesia. NP resulted from the nervous system damage induced by trauma (such as brain injury and spinal) and multiple disorders (such as malignant tumors, stroke and diabetics) [1]. Medical expense of NP is increasing year by year. NP becomes a major public health problem in the world, and a global burden of medical systems [2]. NP usually companied with an unsatisfactory treatment outcome due to partly drugs not suitable to europathic pain, and in primary care, the contribution of neuropathy to pain was unrecognized [3]
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