Proposed model of botulinum toxin-induced muscle weakness in the rabbit

Abstract

Osteoarthritic patients show only a weak association between radiographic signs of joint disease and joint pain and disability. Conversely, muscle weakness is one of the earliest and most common symptoms of patients with osteoarthritis (OA). However, while many experimental models of osteoarthritis include a component of muscular weakness, no model has isolated this factor satisfactorily. Therefore, the purpose of this study was to develop and validate an experimental animal model of muscle weakness for future use in the study of OA. Botulinum Type-A toxin (BTX-A) was uni-laterally injected into the quadriceps musculature of New Zealand white rabbits (3.5 unitdkg). Isometric knee extensor torque at a range of knee angles and stimulation frequencies, and quadriceps muscle mass, were quantified for control animals, and at one-and six-months post-repeated injections, in both, the experimental and the contralateral hindlimb. Ground reaction forces were measured in all animals while hopping across two force platforms. Isometric knee extension torque and quadriceps muscle mass was systematically decreased in the experimental hindlimb. Vertical ground reaction forces in the push off phase of hopping were also decreased in the experimental compared to control hindlimbs. We conclude that BTX-A injection into the rabbit musculature creates functional and absolute muscle weakness in a reproducible manner. Therefore, this model may be used to systematically study the possible effects of muscle weakness on joint degeneration, either as an isolated intervention, or in combination with other interventions (anterior cruciate ligament transection, meniscectomy) known to create knee joint degeneration.

Effects of treadmill running on rat gastrocnemius function following botulinum toxin A injection

“…Our experiments have several implications for clinicians. One of the major effects of local BoNT‐A injection was local muscle weakness and muscle atrophy 37. In cosmetic applications, the atrophy effect of BoNT‐A injection is used for gastrocnemius muscle toning 38.…”

Vertical ground reaction forces diminish in mice after botulinum toxin injection

“…Longino et al (2005) found that in rabbits with BTX injected to the quadriceps (35 U/100 g), peak vertical GRFs were up to 50% lower in BTX-injected rabbits than controls six months post-injection. However, to our knowledge, weight-bearing activity has never been quantified in rodents after BTX injection.…”

Changes in contractile properties of muscles receiving repeat injections of botulinum toxin (Botox)

“…Each half was subdivided into medial, central and lateral section. One sixth of the total botox dose was injected into each section to increase botox diffusion and to inject directly into the vastus lateralis, rectus femoris and vastus medialis muscles (Longino et al, 2005b;Yaraskavitch et al, 2008).…”