Direct Inhibition of Microglia Activation by Pretreatment With Botulinum Neurotoxin A for the Prevention of Neuropathic Pain

Feng，Xiaona1,2; Xiong，Donglin3; Li，Jie4; Xiao，Lizu3; Xie，Weijiao1,3; Qiu，Yunhai1,3

2021-12-07

10.3389/fnins.2021.760403

Frontiers in Neuroscience   影响因子和分区

1662-4548

1662-453X

Peripheral injection of botulinum neurotoxin A (BoNT/A) has been demonstrated to have a long-term analgesic effect in treating neuropathic pain. Around peripheral nerves, BoNT/A is taken up by primary afferent neurons and inhibits neuropeptide release. Moreover, BoNT/A could also be retrogradely transported to the spinal cord. Recent studies have suggested that BoNT/A could attenuates neuropathic pain by inhibiting the activation of spinal glial cells. However, it remains unclear whether BoNT/A directly interacts with these glial cells or via their interaction with neurons. Our aim here is to determine the direct effect of BoNT/A on primary microglia and astrocytes. We show that BoNT/A pretreatment significantly inhibits lipopolysaccharide (LPS) -induced activation and pro-inflammatory cytokine release in primary microglia (1 U/mL BoNT/A in medium), while it has no effect on the activation of astrocytes (2 U/mL BoNT/A in medium). Moreover, a single intrathecal pre-administration of a low dose of BoNT/A (1 U/kg) significantly prohibited the partial sciatic nerve ligation (PSNL)- induced upregulation of pro-inflammatory cytokines in both the spinal cord dorsal horn and dorsal root ganglions (DRGs), which in turn prevented the PSNL-induced mechanical allodynia and thermal hyperalgesia. In conclusion, our results indicate that BoNT/A pretreatment prevents PSNL-induced neuropathic pain by direct inhibition of spinal microglia activation.

BoNT/A intrathecal administration botulinum neurotoxin A (BoNT/A) microglia activation neuropathic pain pretreatment

SCI

英语

其他

Joint Laboratory for Basic Research of Neuropathic Pain undertaking by Shenzhen Institutes of Advanced Technology and Nanshan Hospital of Shenzhen[Y4Z050]

Neurosciences & Neurology

Neurosciences

WOS:000741955600001

FRONTIERS MEDIA SA

2-s2.0-85121632772

Scopus

1.Research Center for Neural Engineering,Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences,Shenzhen,China
2.School of Medicine,Southern University of Science and Technology,Shenzhen,China
3.Shenzhen Municipal Key Laboratory for Pain Medicine,Department of Pain Medicine,Shenzhen Nanshan People’s Hospital,The 6th Affiliated Hospital,Shenzhen University Health Science Center,Shenzhen,China
4.Department of Anesthesiology,Shenzhen Second People’s Hospital,Shenzhen,China

Feng，Xiaona,Xiong，Donglin,Li，Jie,et al. Direct Inhibition of Microglia Activation by Pretreatment With Botulinum Neurotoxin A for the Prevention of Neuropathic Pain[J]. Frontiers in Neuroscience,2021,15.

Feng，Xiaona,Xiong，Donglin,Li，Jie,Xiao，Lizu,Xie，Weijiao,&Qiu，Yunhai.(2021).Direct Inhibition of Microglia Activation by Pretreatment With Botulinum Neurotoxin A for the Prevention of Neuropathic Pain.Frontiers in Neuroscience,15.

Feng，Xiaona,et al."Direct Inhibition of Microglia Activation by Pretreatment With Botulinum Neurotoxin A for the Prevention of Neuropathic Pain".Frontiers in Neuroscience 15(2021).