Mechano- and metabosensitive alterations after injection of botulinum toxin into gastrocnemius muscle

Abstract

This study was designed to investigate effects of motor denervation by Clostridium botulinum toxin serotype A (BoNT/A) on the afferent activity of fibers originating from the gastrocnemius muscle of rats. Animals were randomized in two groups, 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle. Locomotor activity was evaluated once per day during 12 days with a test based on footprint measurements of walking rats (sciatic functional index). At the end of the functional assessment period, electrophysiological tests were used to measure muscle properties, metabosensitive afferent fiber responses to chemical (KCl and lactic acid) injections, electrically induced fatigue (EIF), and mechanosensitive responses to tendon vibrations. Additionally, ventilatory response was recorded during repetitive muscle contractions. Then, rats were sacrificed, and the BoNT/A-injected muscles were weighed. Twelve days postinjection we observed a complete motor denervation associated with a significant muscle atrophy and loss of force to direct muscle stimulation. In the BoNT/A group, the metabosensitive responses to KCl injections were unaltered. However, we observed alterations in responses to EIF and to 1 mM of lactic acid (which induces the greatest activation). The ventilatory adjustments during repetitive muscle activation were abolished, and the mechanosensitive fiber responses to tendon vibrations were reduced. These results indicate that BoNT/A alters the sensorimotor loop and may induce insufficient motor and physiological adjustments in patients in whom a motor denervation with BoNT/A was performed.

Long-Term Effects of Botulinum Toxin Complex Type A Injection on Mechano- and Metabo-Sensitive Afferent Fibers Originating from Gastrocnemius Muscle

“…In the B0 group, measurement of the SFI indicated that functional loss started the first day post-injection, reached a minimal value the third day and remained at this minimum until the twelfth day (when electrophysiological recordings were performed). As previously shown [ 19 ], this functional score was significantly lower (p<0.001) than those recorded before injection or in Control group. No difference was observed with the B50 and B100 groups.…”

“…As previously described, effects of this toxin start between 2 and 5 days after injection and are maintained between 3 and 6 months [ 1 ]. Furthermore, it was also described that functional loss was still maximal at the twelfth day [ 19 ].…”

“…There was a 10 min delay between each injection in order to let the afferent activity go back to its baseline activity. Thus, like in a previous study [ 19 , 27 ] the dose/response curves to KCl and LA from femoral nerve were drawn.…”

“…At the spinal level, these changes reduce the direct excitation of agonist motoneurons and the indirect inhibition of antagonist motoneurons leading to a larger relaxation of agonist muscle (BoNT/A treated)[ 17 ]. Thus, the BoNT/A alters the central adjustments by mechanosensitive (Ia and II from muscle spindle and Ib from Golgi tendon organ)[ 18 ] and metabosensitive (III and IV) muscle afferent fibers [ 19 ]. Ia afferents detect muscle length and velocity while II afferents are mainly sensitive to instantaneous changes in muscle length [ 18 , 20 ].…”

“…In a recent paper, we show that BoNT/A induces alterations in mechano- and metabosensitive afferent fibers when the muscle is to its paralysis apogee [ 19 ]. However, data are missing when the toxin is degraded and during muscle recovery.…”