Reduction of adhesion formation after knee surgery in a rat model by botulinum toxin A

Abstract

Adhesion of the knee is a major concern after knee surgery, the treatment of which is difficult. Botulinum toxin A (BTX-A) injection is demonstrated as efficient in treating knee adhesion after surgery. However, the treatment outcomes and the mechanism of action are not yet determined. The aim of the present study was to examine the effects and molecular mechanism of a BTX-A treatment in preventing adhesion of the knee. Twenty-four Wistar rats were randomly divided into a BTX-A treatment group and a control group. BTX-A or saline was injected into the cavity of the knee in the BTX-A treatment or control group respectively. Gross and histopathological examinations of interleukin 1 (IL-1) and fibroblast growth factor (FGF) levels, as well as fibroblast cell numbers, were assessed in the knee intra-articular adhesions in each group 6 weeks after recovery from the surgery. Macroscopic observations showed a significant reduction in adhesion severity in the BTX-A treatment group compared with the control group. In addition, the levels of IL-1 and FGF were lower and the number of fibroblasts was smaller in the BTX-A treatment group compared with those in the control group. BTX-A prevented intra-articular adhesion of knee in the rats, which might be associated with reduced expressions of IL-1 and FGF.

Intra-Articular Injection of Mitomycin C Prevents Progression of Immobilization-Induced Arthrogenic Contracture in the Remobilized Rat Knee

“…Fibrosis in joint components strongly contributes to progressing arthrogenic contracture in remobilized (Kaneguchi et al 2017, Kaneguchi et al 2018a, Kaneguchi et al 2018b as well as injured joints (Fukui et al 2000, Fukui et al 2001, Gao et al 2017, Li et al 2013a. Further, we observed increased joint capsule thickness and collagen density in the joint capsule following remobilization together with progressing arthrogenic contracture.…”

“…We previously showed that anti-inflammatory treatment using the steroidal drug dexamethasone can prevent remobilization-induced arthrogenic contracture progression by suppressing joint capsule fibrosis and fibroblast proliferation (Kaneguchi et al 2018b). Other studies using intra-articular adhesion models also reported that administration of anti-inflammatory agents such as celecoxib and botulinum toxin type A attenuates joint contracture and intra-articular adhesion as well as fibroblast proliferation (Baranowski et al 2019, Gao et al 2017, Li et al 2013a. Fibroblasts produce extracellular matrix proteins such as collagens, and thus fibroblast proliferation is an important process in the development of joint fibrosis (Emami et al 2012.…”

“…Fibrosis in the joint components is believed to be the major factor contributing to development of arthrogenic contracture in injured (Fukui et al 2000, Fukui et al 2001, Gao et al 2017, Li et al 2013a and immobilized joints (Sasabe et al 2017). For example, administration of decorin, which suppresses bioactivity of cell adhesion, as well as fibrotic regulators, such as transforming growth factor-beta, can improve restricted joint motion in the rabbit intra-articular adhesion model (Fukui et al 2001).…”

<p>Effects of losartan and atorvastatin on the development of early posttraumatic joint stiffness in a rat model</p>

“…In the existing studies on medical inhibition of the development of joint contracture (Table 2), an improvement of the range of motion could be achieved mostly after intraarticular application of the respective active agents. 16,17,64,[95][96][97][98][99][100][101][102][103][104] Although these results constitute an opportunity for the development of a medical treatment of patients with PTJS, the intraarticular application is unfavorable for a number of reasons: i) it is a painful and invasive procedure for the patient, ii) it bears the risk of septic arthritis, iii) it might damage the articular cartilage by chondrotoxic effects or iv) weaken the capsule and ligaments of the knee. [105][106][107] Based on the rabbit models of PTJS of Hildebrand et al and Nesterenko et al, our group established a rat model of PTJS of the knee joint that included a rupture of the posterior joint capsule, a hemarthrosis, an intraarticular bone damage and a temporary fixation of the joint.…”

Comparison of intra-articular administration of adenosine, lidocaine and magnesium solution and tranexamic acid for alleviating postoperative inflammation and joint fibrosis in an experimental model of knee arthroplasty

“…The extension range of motion (ROM), or the angle between the longitudinal axis of the femur and the tibia, was measured in triplicate using an angulometer with 20 g force for both the right (implanted) and left (native, control) knee [ 32 ]. Data are expressed as the difference in extension ROM between the native and implanted knee from TXA- and ALM-treated animals.…”