title: Botulinum toxin injection causes hyper-reflexia and increased muscle stiffness of the triceps surae muscle in the rat.
abstract: Botulinum toxin is used with the intention of diminishing spasticity and reducing the risk of development of contractures. Here, we investigated changes in muscle stiffness caused by reflex activity or elastic muscle properties following botulinum toxin injection in the triceps surae muscle in rats. Forty-four rats received injection of botulinum toxin in the left triceps surae muscle. Control measurements were performed on the noninjected contralateral side in all rats. Acute experiments were performed, 1, 2, 4, and 8 wk following injection. The triceps surae muscle was dissected free, and the Achilles tendon was cut and attached to a muscle puller. The resistance of the muscle to stretches of different amplitudes and velocities was systematically investigated. Reflex-mediated torque was normalized to the maximal muscle force evoked by supramaximal stimulation of the tibial nerve. Botulinum toxin injection caused severe atrophy of the triceps surae muscle at all time points. The force generated by stretch reflex activity was also strongly diminished but not to the same extent as the maximal muscle force at 2 and 4 wk, signifying a relative reflex hyperexcitability. Passive muscle stiffness was unaltered at 1 wk but increased at 2, 4, and 8 wk (P < 0.01). These data demonstrate that botulinum toxin causes a relative increase in reflex stiffness, which is likely caused by compensatory neuroplastic changes. The stiffness of elastic elements in the muscles also increased. The data are not consistent with the ideas that botulinum toxin is an efficient antispastic medication or that it may prevent development of contractures.
authors.affiliation: Neural Control of Movement Research Group, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jessica
authors.initials: J
authors.lastname: Pingel
authors.affiliation: Department of Nutrition, Exercise and Sport, University of Copenhagen, Copenhagen, Denmark; and.
authors.forename: Jacob
authors.initials: J
authors.lastname: Wienecke
authors.affiliation: Neural Control of Movement Research Group, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.|Elsass Institute, Charlottenlund, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Lorentzen
authors.affiliation: Neural Control of Movement Research Group, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark; jbnielsen@sund.ku.dk.|Elsass Institute, Charlottenlund, Denmark.
authors.forename: Jens Bo
authors.identifier: 0000-0001-5568-2916
authors.initials: JB
authors.lastname: Nielsen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000633:toxicity*; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000187:drug effects; D006614:Hindlimb / Q000294:innervation; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects*; D009465:Neuromuscular Agents / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012021:Reflex, Abnormal / Q000187:drug effects*; D013035:Spasm / Q000139:chemically induced*; D013997:Time Factors
chemical_list: D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A
keywords: botulinum toxin; muscle stiffness; plasticity; reflex; spinal cord