Unilateral facial injection of Botulinum neurotoxin A attenuates bilateral trigeminal neuropathic pain and anxiety-like behaviors through inhibition of TLR2-mediated neuroinflammation in mice

The Journal of Headache and Pain

Yi-Ting Chen¹  Jing Liu²  Ying-Ying Xu²  Wei-Jia Chen²  Wen-Jing Deng²  Wei-Feng Luo³  Jing-Qi Niu⁴  Tong Liu⁵ 

[1] Changzhou Hygiene Vocational Technology College, 213002, Changzhou, China;Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, 215004, Suzhou, China;Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, 215004, Suzhou, China;Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric-Diseases, Soochow University, 215021, Suzhou, China;Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, 215004, Suzhou, China;The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, Hefei, Anhui, China;Institute of Pain Medicine and Special Environmental Medicine, Nantong University, 226019, Nantong, China;College of Life Sciences, Yanan University, 716000, Yanan, China;Suzhou Key Laboratory of Intelligent Medicine and Equipment, 215123, Suzhou, China;

关键词: Trigeminal neuralgia;    Anxiety;    Microglia;    Innate immunity;    Toll-like receptor 2 (TLR2);    Botulinum toxin type A;   

DOI  :  10.1186/s10194-021-01254-2

来源: Springer

【 摘 要 】

ObjectivesIn this study, we investigated the possible analgesic effects of Botulinum toxin type A (BoNT/A) on trigeminal neuralgia (TN). A modified TN mouse model was established by chronic constriction injury of the distal infraorbital nerve (dIoN-CCI) in mice, and the possible roles of microglia toll-like receptor 2 (TLR2) and neuroinflammation was investigated.MethodsMale C57BL/6 mice were divided into 3 groups, including sham group, vehicle-treated TN group and BoNT/A-treated TN group. Bilateral mechanical pain hypersensitivity, anxiety-like and depressive-like behaviors were evaluated by using von Frey test, open field, elevated plus-maze testing, and forced swimming test in mice, respectively. The mRNA or protein expression levels of toll-like receptors (TLRs), glia activation markers and proinflammatory factors in the trigeminal nucleus caudalis (TNC) were tested by RT-qPCR, immunofluorescence and Western blotting. We also tested the pain behaviors of TN in Tlr2−/− mice.ResultsWe found that unilateral subcutaneous injection of BoNT/A into the whisker pad on the ipsilateral side of dIoN-CCI mice significantly attenuated bilateral mechanical pain hypersensitivity and anxiety-like behaviors induced by dIoN-CCI surgery in mice. The dIoN-CCI surgery significantly up-regulated the expression of TLR2, MyD88, CD11b (a microglia marker), IL-1β, TNF-α and IL-6 in the ipsilateral TNC in mice, and BoNT/A injection significantly inhibited the expression of these factors. Immunostaining results confirmed that BoNT/A injection significantly inhibited the microglia activation in the ipsilateral TNC in dIoN-CCI mice. TLR2 deficiency also alleviated bilateral mechanical pain hypersensitivity and the up-regulation of MyD88 expression in the TNC of dIoN-CCI mice.ConclusionThese results indicate that unilateral injection of BoNT/A attenuated bilateral mechanical pain hypersensitivity and anxiety-like behaviors in dIoN-CCI mice, and the analgesic effects of BoNT/A may be associated with the inhibition of TLR2-mediated neuroinflammation in the TNC.

【 授权许可】

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