title: Intra-articular injection of Botulinum toxin A reduces neurogenic inflammation in CFA-induced arthritic rat model.
abstract: Currently, administration of Botulinum toxin Type A (BoNT/A) to treat arthritic pain has promising efficacy in clinical research. However, the mechanisms underlying anti-neurogenic inflammation mediated by BoNT/A remains unclear. The aim of this study was to demonstrate the effectiveness in macro and micro levels and to explore the causal mechanism of BoNT/A. Wistar rats (n = 60) were injected with 50ul complete Freund's adjuvant (CFA) in the left ankle joint capsule to establish a model of chronic monoarthritis. Pain behaviour (Evoked pain assessment) and infrared thermal imaging testing were performed at the macroscopic level to assess the effectiveness of analgesia and anti-inflammation. Western blotting and immunofluorescence staining were used at the microscopic level in an attempt to determine the mechanisms of anti-nociceptive or anti-inflammatory effects of BoNT/A. Additionally, hematoxylin-eosin staining was also used to visualise the cartilage and the synovial degenerative conditions of arthritis. By comparing the outcome of the evoked pain test and immunofluorescence staining, there was a significant improvement in BoNT/A compared with the normal saline (NS) injected control group. In addition, thermal variations showed that the temperature of ipsilateral ankle joint increased between 1 and 2 weeks following injection of CFA, but decreased after 3 weeks (still above the contralateral side). However, the temperature showed no difference between the BoNT/A group and NS group after treatment. The expression of IL-1β or TNF-α in the ankle synovial tissue was significantly decreased in the BoNT/A group compared to the NS group (p < 0.05). Based on the HE assessment, cartilage degeneration and infiltration of inflammatory cells in the BoNT/A group was alleviated compared to the NS group after treatment. In conclusion, we proposed the hypothesis that intra-articular BoNT/A administration does play an important role in anti-neurogenic inflammation. The possible mechanisms might be that BoNT/A prevents the release of nociceptive nerve peptides at the injection site and then suppresses the expression of inflammatory cytokines.
authors.affiliation: Department of Rehabilitation Medicine, The Affiliated Hospital of QingDao University, Jiangsu Road, Qingdao 266003, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Rehabilitation Medicine, The People's Hospital of Rizhao, Taian Road, Rizhao 276800, PR China.
authors.forename: Kaile
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, QingDao Municipal Hospital, East Sea Middle Road, Qingdao 266000, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chu
authors.affiliation: Department of Rehabilitation Medicine, The Affiliated Hospital of QingDao University, Jiangsu Road, Qingdao 266003, PR China. Electronic address: tieshanl@126.com.
authors.forename: Tieshan
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Rehabilitation Medicine, The Affiliated Hospital of QingDao University, Jiangsu Road, Qingdao 266003, PR China.
authors.forename: Nana
authors.initials: N
authors.lastname: Shen
authors.affiliation: Department of Rehabilitation Medicine, The Affiliated Hospital of QingDao University, Jiangsu Road, Qingdao 266003, PR China.
authors.forename: Chenglei
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Rehabilitation Medicine, The Affiliated Hospital of QingDao University, Jiangsu Road, Qingdao 266003, PR China.
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Niu
authors.affiliation: Department of Respiratory, YanTai Shan Hospital, Yantai 264001, PR China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Rehabilitation Medicine, The Affiliated Hospital of QingDao University, Jiangsu Road, Qingdao 266003, PR China.
authors.forename: Luoman
authors.initials: L
authors.lastname: Hu
mesh_terms: D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D005620:Freund's Adjuvant; D007270:Injections, Intra-Articular; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D020078:Neurogenic Inflammation; D017208:Rats, Wistar
chemical_list: D053583:Interleukin-1beta; D005620:Freund's Adjuvant; D019274:Botulinum Toxins, Type A; D015740:Calcitonin Gene-Related Peptide
keywords: Botulinum toxin A; Neurogenic inflammation; Rat model of chronic monoarthritis