Non-uniform Effects of Nociceptive Stimulation to Motoneurones during Experimental Muscle Pain.

Nociceptive stimulation is predicted to uniformly inhibit motoneurone pools of painful muscles and those producing painful movements. Although reduced motoneurone discharge rate during pain provides some evidence, recent data show evidence of increased excitability of some motoneurones. These observations suggest non-uniform effects of nociception on motoneurone excitability. More direct measures are required, but this is difficult to assess as few measures enable in vivo evaluation of motoneurone excitability in humans. We investigated changes in motoneurone excitability during experimental pain using two methods in separate experiments: (i) estimation of the time-course of motoneurone afterhyperpolarization (AHP) from interval death rate analysis of interspike intervals of single motor unit discharge; and (ii) probability of early motoneurone discharge to a descending volley excited using transcranial magnetic stimulation (TMS). Tibialis anterior motor units were recorded with fine-wire electrodes before, during and after painful infusion of 5% hypertonic saline into the muscle. Activation of 17 units (16 participants) could be used for AHP analysis. Data show shortened (n = 11) and lengthened (n = 6) AHP time-course. Increased (n = 6) and decreased (n = 6) probability of early motoneurone discharge were observed in the TMS experiment. These convergent observations suggest non-uniform effects of nociceptive stimulation on motoneurone pools. This does not support the hypothesis that nociceptive input induces uniform inhibition of painful muscle. Instead, interpretation of results implies redistribution of activity between motor units, with possible benefit for unloading painful tissues. This finding supports an interpretation that differs from the generally accepted view in pain physiology regarding adaptation to motor function in pain.

Mechanisms and functional implications of motoneuron adaptations to increased physical activity.

Motoneurons demonstrate adaptations in their physiological properties to alterations in chronic activity levels. The most consistent change that appears to result from endurance-type exercise training is the reduced excitatory current required to initiate and maintain rhythmic firing. While the precise mechanisms through which these neurons adapt to activity are currently unknown, evidence exists that adaptation may involve alterations in the expression of genes that code for membrane receptors, which can influence the responses of neurons to transmitters during activation. The influence of these adaptations may also extend to the resting condition, where ambient levels of neuroactive substances may influence ion conductances at rest, and thus result in the activation or inhibition of specific ion conductances that underlie the measurements of increased excitability that have been reported for motoneurons in the anesthetised state. We have applied motoneuron excitability and muscle unit contractile changes with endurance training to a mathematical computerized model of motor unit recruitment (Heckman and Binder 1991; J. Neurophysiol. 65(4):952-967). The results from the modelling exercise demonstrate increased task efficiency at relative levels of effort during a submaximal contraction. The physiological impact that nerve and muscle adaptations have on the neuromuscular system during standardized tasks seem to fit with reported changes in motor unit behaviour in trained human subjects.

Altered transcription of glutamatergic and glycinergic receptors in spinal cord dorsal horn following spinal cord transection is minimally affected by passive exercise of the hindlimbs.

Gene expression is altered following a spinal transection (STx) in both motor and sensory systems. Exercise has been shown to influence gene expression in both systems post-STx. Gene expression alterations have also been shown in the dorsal root ganglia and nociceptive laminae of the spinal cord following either an incomplete spinal cord injury (SCI) or a contusive SCI. However, the effect of STx and exercise on gene expression in spinal cord laminae I-III has not fully been examined. Therefore, the purpose of this study was to determine whether gene expression in laminae I-III is altered following STx and determine whether superimposed passive exercise of the hindlimbs would influence gene expression post-STx in laminae I-III. Laser capture microdissection was used to selectively harvest laminae I-III of lumbar spinal cord sections, and quantitative RT-PCR was used to examine relative expression of 23 selected genes in samples collected from control, STx and STx plus exercise rats. We demonstrate that post-STx, gene expression for metabotropic glutamate receptors 1, 5 and 8 were up-regulated, whereas ionotropic glutamatergic receptor (Glur2) and glycinergic subunit GLRA1 expression was down-regulated. Daily exercise attenuated the down-regulation of Glur2 gene expression in laminae I-III. Our results demonstrate that in a STx model, gene expression is altered in laminae I-III and that although passive exercise influences gene expression in both the motor and sensory systems, it had a minimal effect on gene expression in laminae I-III post-STx.

α-Motoneurons maintain biophysical heterogeneity in obesity and diabetes in Zucker rats.

Small-diameter sensory dysfunction resulting from diabetes has received much attention in the literature, whereas the impact of diabetes on α-motoneurons (MN) has not. In addition, the chance of developing insulin resistance and diabetes is increased in obesity. No study has examined the impact of obesity or diabetes on the biophysical properties of MN. Lean Zucker rats and Zucker diabetic fatty (ZDF) rats were separated into lean, obese (ZDF fed standard chow), and diabetic (ZDF fed high-fat diet that led to diabetes) groups. Glass micropipettes recorded hindlimb MN properties from identified flexor and extensor MN. MN were separated within their groups on the basis of input conductance, which created high- and low-input conductance subpopulations for each. A significant shorter (20%) afterhyperpolarization half-decay (AHP1/2) was found in low-conductance MN for the diabetic group only, whereas AHP½ tended to be shorter in the obese group (19%). Significant positive correlations were found among rheobase and input conductance for both lean and obese animals. No differences were found between the groups for afterhyperpolarization amplitude (AHPamp), input conductance, rheobase, or any of the rhythmic firing properties (frequency-current slope and spike-frequency adaptation index). MN properties continue to be heterogeneous in obese and diabetic animals. Obesity does not seem to influence lumbar MN. Despite the resistance of MN to the impact of diabetes, the reduced AHP1/2 decay and the tendency for a reduction in AHPamp may be the first sign of change to MN function.NEW & NOTEWORTHY Knowledge about the impact of obesity and diabetes on the biophysical properties of motoneurons is lacking. We found that diabetes reduces the duration of the afterhyperpolarization and that motoneuron function is unchanged by obesity. A reduced afterhyperpolarization may impact discharge characteristics and may be the first sign of change to motoneuron function.

Daily passive cycling attenuates the hyperexcitability and restores the responsiveness of the extensor monosynaptic reflex to quipazine in the chronic spinally transected rat.

Activity-based interventions such as locomotor training or passive cycling have a positive influence on the spinal circuitry and recovery following a spinal cord injury (SCI). The use of quipazine in combination with exercise training has demonstrated a greater functional recovery than has exercise training alone. However, the influence of exercise or training on the responsiveness of the spinal cord to quipazine has not been examined following a chronic spinal transection. The purpose of this study was to characterize the flexor and extensor monosynaptic reflex (MSR) response pre- and post-quipazine in chronic complete spinally transected rats that either underwent daily passive cycling for 3 months or did not receive passive cycling. Following a chronic spinal transection, the extensor MSR demonstrated a hyperreflexive response (fivefold increase) to afferent stimuli, and did not respond to quipazine injection. With daily passive cycling, the extensor MSR hyperexcitability was attenuated, and the MSR amplitude increased 72% following quipazine injection (p<0.004), which was comparable to the extensor MSR response (94%) in the control group. For both chronic spinal transection groups, the flexor MSR amplitudes were not altered following quipazine injection, whereas in the control group the flexor MSR amplitude increased 86% in response to quipazine (p<0.004). These results demonstrate that passive cycling attenuates the hyperreflexive response of the extensor MSR following a chronic SCI, and restores the MSR response to quipazine.

Motoneurone afterhyperpolarisation time-course following stroke.

OBJECTIVE: Our aim was to investigate any changes in the estimated time-course of the afterhyperpolarisation (AHP) in motoneurones innervating the tibialis anterior following stroke, with a secondary objective to compare the results from two different AHP estimation techniques. METHODS: Motor units from tibialis anterior on the paretic and non-paretic sides of 15 subjects with chronic stroke were recorded using intramuscular electrodes during voluntary isometric contraction. Participants varied the motor unit firing rate from its lowest rate to approximately 10 Hz. The AHP duration was estimated using the interval death rate (IDR) and transition point methods. RESULTS: The AHP decay time-constant was significantly different between sides (paretic: 41.7 ± 8.5 ms, non-paretic: 36.2 ± 6.4 ms). Additionally, the paretic AHP time-constant was significantly longer in participants with low motor recovery (45.9 ± 9.1 ms) than with high motor recovery (39.3 ± 10.0 ms) as measured by CMSA score. The AHP estimates from the two techniques were correlated (r=0.78). CONCLUSIONS: The AHP time-course prolongation on the paretic side of people with chronic stroke is more pronounced in people with low motor recovery. SIGNIFICANCE: Changes in the motoneurone AHP time course post-stroke were related to muscle function and may play a role in the commonly-observed reduction of motor unit discharge rate during voluntary contractions following stroke.

Removal of supraspinal input reveals a difference in the flexor and extensor monosynaptic reflex response to quipazine independent of motoneuron excitation.

The purpose of this study was to determine if quipazine, a serotonergic agonist, differentially modulates flexor and extensor motor output. This was achieved by examining the monosynaptic reflex (MSR) of the tibial (extensor) and peroneal (flexor) nerves, by determining the basic and rhythmic properties of extensor and flexor motoneurons, and by recording extracellular Ia field potentials of the tibial and peroneal nerves in the in vivo adult decerebrate rat in both spinal intact and acute spinalized preparations. In the spinal intact preparation, the tibial and peroneal MSR amplitude significantly increased compared with baseline in response to quipazine, with no difference between nerves (P < 0.05). In the spinalized preparation, the MSR was significantly increased in both the tibial and peroneal nerves with the latter increasing more than the former (5.7 vs. 3.6 times; P < 0.05). Intracellular motoneuron experiments demonstrated that rheobase decreased, while input resistance, afterhyperpolarization amplitude, and the firing rate at a given current injection increased in motoneurons following quipazine administration with no differences between extensor and flexor motoneurons. Both the tibial and peroneal nerve extracellular Ia field potentials increased with the peroneal demonstrating a significantly greater increase (7 vs. 38%; P < 0.05) following quipazine. It is concluded that in the spinal intact preparation quipazine does not have a differential effect on flexor or extensor motor output. However, in the acute spinalized preparation, quipazine preferentially affects the flexor MSR compared with the extensor MSR, likely due to the removal of a descending tonic inhibition on flexor Ia afferents.

Changes in the estimated time course of the motoneuron afterhyperpolarization induced by tendon vibration.

Group Ia afferents are activated vigorously with high-frequency tendon vibration and provide excitatory input to the agonist muscle and inhibitory input to the antagonist muscle group via inhibitory interneurons. The purpose of this experiment was to determine whether the afterhyperpolarization (AHP) time course in humans is altered in response to tendon vibration. The AHP time course is estimated using the interval death rate (IDR) analysis, a transform of the motor unit action potential train. Single motor units from tibialis anterior (TA) were recorded as subjects held low force dorsiflexor contractions for 600 s with and without vibration. The vibratory stimulus was superimposed on the low force contraction either to the tendon of the TA or the antagonist Achilles tendon. During TA tendon vibration, the time course of the AHP, as expressed by its time constant (τ), decreased from 35.5 ms in the previbration control condition to 31.3 ms during the vibration (P = 0.003) and returned to 36.3 ms after the vibration was removed (P = 0.002). The AHP τ during vibration of the antagonist Achilles tendon (38.6 ms) was greater than the previbration control condition (33.6 ms; P = 0.001). It is speculated that the reduction in AHP time constant with TA vibration may have resulted alone or in combination with a modulation of motoneuron gain, an alteration of persistent inward currents and/or the restructuring of synaptic noise. A decrease in firing probability, possibly reflecting Ia reciprocal inhibition, may have been responsible for the larger AHP time constant.

Afterhyperpolarization time-course and minimal discharge rate in low threshold motor units in humans.

The alpha-motoneurone afterhyperpolarization (AHP) duration correlates with a number of its muscle unit properties in animal preparations. In humans, the interval death rate (IDR) analysis has been used to estimate the time course of human motoneurone AHP based on the pattern of motor unit firing. The purpose of this experiment was first, to examine the relationship between estimated AHP time course and the minimal firing rate of the motor unit and second, to examine the relationship between the AHP and motor unit contractile properties in the tibialis anterior (TA) muscle. Motor unit data were obtained from the TA muscle during low force isometric contractions lasting 600 s. Muscle unit twitch characteristics were determined using spike-triggered averaging (STA) and the motoneurone AHP time course was estimated using the IDR analysis. Minimal discharge rate and derecruitment threshold torque were determined for 2 s preceding motor unit derecruitment. The AHP time constant and minimal discharge rate were negatively correlated, whereas the derecruitment threshold torque was not associated with the AHP time constant. The estimated AHP duration, however, is considerably shorter than the mean ISI of the minimal discharge rate suggesting that synaptic noise and AHP duration are important factors in dictating the minimal discharge rate in low force voluntary contractions in humans. The AHP time constant did not vary significantly with motor unit twitch amplitude; however, significant positive relationships were found between the AHP time constant and the temporal properties of the motor unit twitch. The calculated AHP time course using the IDR analysis, therefore, is a reasonable estimate and coupled with motor unit properties attained with STA, it provides a powerful method to describe low-threshold motor units.

Interfering effects of the task demands of grip force and mental processing on isometric shoulder strength and muscle activity.

The purpose of this study was to examine the interfering effects of physical and mental tasks on shoulder isometric strength in different postures. Fifteen volunteers (seven women, eight men) performed a series of isometric shoulder exertions at 30 degrees , 60 degrees and 90 degrees of both shoulder flexion and abduction alone and with the addition of a 30% grip force, a mental task (Stroop test) and both additional tasks simultaneously. The shoulder tasks were completed either at maximal intensity, or while maintaining a shoulder posture without any additional effort. Surface electromyography (EMG) from seven muscles of the shoulder girdle and shoulder moment were collected for each 6 s shoulder exertion. When normalized to maximum exertion, no differences were found between genders and no differences existed between conditions when subjects maintained each posture without exerted force. In the maximal shoulder exertion trials, an increase in shoulder angle (in either plane) resulted in an increase in EMG in most muscles, while shoulder moment decreased in flexion and remained constant in abduction. Shoulder moments and muscle activation were greatest in the shoulder exertion alone condition followed by adding a 30% grip and the Stroop test, with the addition of both tasks further reducing the exerted shoulder moment and EMG. However, muscle activity did not always decrease with shoulder strength and remained elevated, indicating a complex coactivation pattern produced by an interfering role of the tasks. Overall, it was found that a mental task can have the same or greater effect as a concurrent grip and should be considered when assessing muscular loading in the workplace, as typical biomechanical modelling may underestimate internal loads. The results not only provide valuable shoulder strength data but also practical strength values, depending on additional tasks.

Muscle activity during patient transfers: a preliminary study on the influence of lift assists and experience.

The purpose of this study was to examine muscle activity patterns during patient handling during manual transfers, and transfers using floor and ceiling lifts. EMG patterns during transfers from bed to wheelchair and wheelchair to bed as well as patient repositioning in novices and experienced participants were examined. Surface EMG was recorded from the upper and lower erector spinae, latissimus dorsi and trapezius muscles bilaterally. Overall, normalized mean and peak muscle activity were lowest using the ceiling lift, increasing with the floor lift, which were lower than manual transfers (novices: all p < 0.01). Experienced patient handlers demonstrated approximately two times greater trapezius and latissimus dorsi activity than novices, combined with lower mean erector spinae activity (p < 0.05, for most tasks). Integrated EMG for all muscles was directly proportional to the transfer time and was lowest during the manual transfer followed by the ceiling lift, with the floor lift being highest. The difference between the muscle activity patterns between the experienced and novice patient handlers may suggest a learned behaviour to protect the spine by distributing load to the shoulder. Further examination of the muscle activation patterns differences between experience levels could improve training techniques to develop better patient handling strategies.