Effects of baclofen on motor units paralysed by chronic cervical spinal cord injury

Abstract

Baclofen, a gamma-aminobutyric acid receptor(B) agonist, is used to reduce symptoms of spasticity (hyperreflexia, increases in muscle tone, involuntary muscle activity), but the long-term effects of sustained baclofen use on skeletal muscle properties are unclear. The aim of our study was to evaluate whether baclofen use and paralysis due to cervical spinal cord injury change the contractile properties of human thenar motor units more than paralysis alone. Evoked electromyographic activity and force were recorded in response to intraneural stimulation of single motor axons to thenar motor units. Data from three groups of motor units were compared: 23 paralysed units from spinal cord injured subjects who take baclofen and have done so for a median of 7 years, 25 paralysed units from spinal cord injured subjects who do not take baclofen (median: 10 years) and 45 units from uninjured control subjects. Paralysed motor unit properties were independent of injury duration and level. With paralysis and baclofen, the median motor unit tetanic forces were significantly weaker, twitch half-relaxation times longer and half maximal forces reached at lower frequencies than for units from uninjured subjects. The median values for these same parameters after paralysis alone were comparable to control data. Axon conduction velocities differed across groups and were slowest for paralysed units from subjects who were not taking baclofen and fastest for units from the uninjured. Greater motor unit weakness with long-term baclofen use and paralysis will make the whole muscle weaker and more fatigable. Significantly more paralysed motor units need to be excited during patterned electrical stimulation to produce any given force over time. The short-term benefits of baclofen on spasticity (e.g. management of muscle spasms that may otherwise hinder movement or social interactions) therefore have to be considered in relation to its possible long-term effects on muscle rehabilitation. Restoring the strength and speed of paralysed muscles to pre-injury levels may require more extensive therapy when baclofen is used chronically.

Figure 1

Median (25th and 75th percentiles) tetanic force (A) and twitch force (B) for units in the Paralysis and Baclofen (P&B), Paralysis (P) and Uninjured (U) groups. Brackets and asterisk indicate statistical significance at *P < 0.05, or **P < 0.01. (C) Median force for each group of units at different stimulation frequencies.

Figure 2

Median motor unit fatigue index over time (A) for units in the Paralysis and Baclofen (n = 8), Paralysis (n = 9) and Uninjured (n = 23) groups. Median number of thenar motor units to produce 1 N of force in these same units (B).

Figure 3

(A). Twitch forces of paralysed units in the Paralysis and Baclofen group (solid lines, n = 3) and Paralysis group (dashed lines, n = 3). (B–D) Median (25th and 75th percentiles) F50 (B), twitch contraction time (C) and half-relaxation time (D) for units in the Paralysis and Baclofen (P&B), Paralysis (P) and Uninjured (U) groups. Brackets and asterisk indicate statistical significance at *P < 0.05 or **P < 0.01.

Figure 4

Median (25th and 75th percentile) axon conduction velocity (A) and EMG duration and (B) for units in the Paralysis and Baclofen (P&B), Paralysis (P) and Uninjured (U) groups. Brackets and asterisk indicate statistical significance at *P < 0.05, or **P < 0.01.