In search of biomarkers for low back pain: can traction therapy effectiveness be prognosed by surface electromyography or blood parameters?

Background: Lumbar traction therapy is a common method to reduce low back pain (LBP) but is not always effective. The search for biomarkers that would prognose the effectiveness of LBP management is one priority for improving patients' quality of life. Objectives: 1) To determine the phenotype of patients benefiting most from lumbar traction therapy. 2) To correlate systemic and electromyographic biomarkers with pain and pain-related disability. Methods: Data on muscle bioelectrical activity (surface electromyography [SEMG]) in the flexion-extension task, the concentrations of twelve systemic biochemical factors, LBP intensity (Visual Analog Scale), the Oswestry Disability Index, and the Roland-Morris Disability Questionnaire (RMDQ) were collected before and 72 h after 20 sessions of lumbar traction therapy. Patients were divided into responders and nonresponders based on the criterion of a 50% reduction in maximal pain. Results: The responders had lower maximal muscle bioactivity in the extension phase on the left side (p < 0.01) and higher flexion-extension ratios on both sides of the body in the SEMG (left: p < 0.05; right: p < 0.01), and higher adipsin, interleukin-2, interleukin-4, and interleukin-10 concentrations (p < 0.05) than nonresponders. Patients with higher interleukin-4 concentrations before therapy achieved greater reductions in maximal pain in the sitting position, bioelectrical muscle activity in flexion, and flexion-relaxation ratio on the left side of the body. Changes in adipsin and interleukin-4 concentrations correlated with changes in LBP intensity (r = 0.68; r = -0.77). Changes in stem cell growth factor and interleukin-17A correlated with changes in RMDQ (R = 0.53) and bioelectrical muscle activity in extension (left: R = -0.67; right: R = -0.76), respectively. Conclusion: Responders to traction therapy had SEMG indices of less favorable muscle activity in the flexion-extension task and elevated indices of inflammation before the study. For the first time, interleukin-4 was indicated as a potential biomarker for prognosing post-therapy changes in pain intensity and muscle activity.

Differences in Ia proprioceptive input to spinal motoneurons between male and female rats.

Male and female rats differ in muscle fibre composition, related motor unit contractile properties, and muscle spindle density but not number. On the other hand, their motoneurons' intrinsic properties, excitability and firing properties are similar. The aim of this study was to investigate whether apparent sex differences in body mass and muscle force influence the proprioceptive input from muscle spindles to motoneurons. Medial gastrocnemius motoneurons were investigated intracellularly in deeply anaesthetised male and female rats. Monosynaptic Ia excitatory postsynaptic potentials (EPSPs) were evoked using electrical stimulation of primary afferents from homonymous muscle. Data were analysed using a mixed linear model. The central latencies of EPSPs were 0.38-0.80 ms, with no differences in means between males and females. The maximum EPSP amplitude varied between 2.03 and 8.09 mV in males and 1.24 and 6.79 mV in females. The mean maximum EPSP amplitude was 26% higher in males than in females. The mean EPSP rise time, half-decay time and total duration did not differ between the sexes. EPSP amplitudes correlated with the resting membrane potential, input resistance and EPSP rise time in both sexes. The observed sex differences in the Ia proprioceptive input may be related either to mechanical loading differences in males and females associated with their different body mass or hormonal differences influencing the levels of neuromodulation in spinal circuits. The results highlight the importance of taking sex into consideration in the studies on the influence of afferent inputs on MN excitability.

Skeletal muscle models composed of motor units: A review.

The mathematical muscle models should include several aspects of muscle structure and physiology. First, muscle force is the sum of forces of multiple motor units (MUs), which have different contractile properties and play different roles in generating muscle force. Second, whole muscle activity is an effect of net excitatory inputs to a pool of motoneurons innervating the muscle, which have different excitability, influencing MU recruitment. In this review, we compare various methods for modeling MU twitch and tetanic forces and then discuss muscle models composed of different MU types and number. We first present four different analytical functions used for twitch modeling and show limitations related to the number of twitch describing parameters. We also show that a nonlinear summation of twitches should be considered in modeling tetanic contractions. We then compare different muscle models, most of which are variations of Fuglevand's model, adopting a common drive hypothesis and the size principle. We pay attention to integrating previously developed models into a consensus model based on physiological data from in vivo experiments on the rat medial gastrocnemius muscle and its respective motoneurons. Finally, we discuss the shortcomings of existing models and potential applications for studying MU synchronization, potentiation, and fatigue.

Influence of altered serum and muscle concentrations of BDNF on electrophysiological properties of spinal motoneurons in wild-type and BDNF-knockout rats.

The purpose of this study was to determine whether altered serum and/or muscle concentrations of brain-derived neurotrophic factor (BDNF) can modify the electrophysiological properties of spinal motoneurons (MNs). This study was conducted in wild-type and Bdnf heterozygous knockout rats (HET, SD-BDNF). Rats were divided into four groups: control, knockout, control trained, and knockout trained. The latter two groups underwent moderate-intensity endurance training to increase BDNF levels in serum and/or hindlimb muscles. BDNF and other neurotrophic factors (NFs), including glial cell-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3), nerve growth factor (NGF), and neurotrophin-4 (NT-4) were assessed in serum and three hindlimb muscles: the tibialis anterior (TA), medial gastrocnemius (MG), and soleus (Sol). The concentrations of tropomyosin kinase receptor B (Trk-B), interleukin-15 (IL-15), and myoglobin (MYO/MB) were also evaluated in these muscles. The electrophysiological properties of lumbar MNs were studied in vivo using whole-cell current-clamp recordings. Bdnf knockout rats had reduced levels of all studied NFs in serum but not in hindlimb muscles. Interestingly, decreased serum NF levels did not influence the electrophysiological properties of spinal MNs. Additionally, endurance training did not change the serum concentrations of any of the NFs tested but significantly increased BDNF and GDNF levels in the TA and MG muscles in both trained groups. Furthermore, the excitability of fast MNs was reduced in both groups of trained rats. Thus, changes in muscle (but not serum) concentrations of BDNF and GDNF may be critical factors that modify the excitability of spinal MNs after intense physical activity.

Subjective assessment and biochemical evaluation of traction therapy in women with chronic low back pain: does body mass index matter? A clinical study.

BACKGROUND: Apart from the positive effect of lumbar traction on structural changes within the spine in patients with low back pain, it is likely that therapeutic effects are correlated with pain biomarkers in the blood. Among them, systemic metabolic factors related to obesity may play an important role. This is the first study designed to examine the effectiveness of traction therapy in two experimental groups with considerably different BMI and to assess relationships between blood biomarkers and low back pain intensity. METHODS: In the prospective clinical trial, women suffering from chronic low back pain were allocated into the normal-weight or obesity groups. Patients in both groups underwent twenty sessions of lumbar traction therapy (30 min a day, continuous mode with a force level of 25-30% of body weight). Before and after therapy subjective assessments of pain (VAS and PPT) were performed, and serum concentrations of aggrecan chondroitin sulfate 846 epitope (CS-846), neuropeptide Y, leptin, adipsin and growth and differentiation factor 15 (GDF-15) were determined. The data were statistically evaluated for 28 women. RESULTS: After therapy, the maximal low back pain decreased in both groups, GDF-15 concentration was reduced in the normal-weight group and increased in the obesity group, and CS-846 concentration decreased in the obesity group. The sensation of PPT in the lumbar spine and mean concentrations of neuropeptide Y, leptin and adipsin did not change in both groups. However, the relationships of GDF-15, leptin, and adipsin concentrations with the perception of pain were revealed. CONCLUSION: Distinct differences between the normal-weight and obesity groups pointed on the role of excessive adipose tissue in aggravating the inflammatory processes and in the development of low back pain. Adipsin, CS-846 and GDF-15 aspire to be the low back pain biomarkers in women with obesity, but there is a need for further research to answer whether they might be considered reliable biomarkers for the prognosis and monitoring of chronic low back treatment. TRIAL REGISTRATION: NCT04507074, registered prospectively on July 6, 2020.

The electrophysiological properties of hindlimb motoneurons do not differ between male and female rats.

Several studies have reported differences in the morphological characteristics of motoneurons and the contractile properties of motor units of male and female rats. However, differences in spinal motoneuron activity between the sexes are not well understood. This study investigates the electrophysiological properties of spinal α-motoneurons in male and female Wistar rats under pentobarbital anaesthesia. Fast and slow types of tibial motoneurons were recorded intracellularly in 15 male and 15 female rats, and the measured parameters were compared statistically using two-way ANOVA and Tukey post hoc tests. The membrane properties, action potential parameters and firing characteristics were not different between sexes, though significant differences were observed in the properties of fast and slow motoneuron types within both sex groups. We conclude that the sex-related differences observed in motor performance between male and female rats are largely due to differences in muscle mass, the proportion of muscle fibre types and the related motor unit contractile properties, while the mechanisms of motor control dependent on the electrophysiological activity of motoneurons are similar between the sexes. These findings are significant, as they indicate that results of experiments investigating electrophysiological properties can be reliably compared between sexes.

Ia EPSPs in rat spinal motoneurons are potentiated after a 5-week whole body vibration.

Whole body vibration (WBV) is often applied as an alternative method for strength training or to prevent muscle force decrease. In this study, we evaluated the influence of WBV on Ia monosynaptic input from muscle spindles because the tonic vibration reflex is responsible for the enhancement of muscle activity observed after WBV. The aim was to investigate whether repeated activation of muscle spindles during WBV may result in altered synaptic excitation of motoneurons. WBV was performed on adult male Wistar rats, 5 days/wk, for 5 wk, and each daily session consisted of four 30-s runs of vibration at 50 Hz. Fast-type medial gastrocnemius motoneurons were investigated intracellularly in deeply anesthetized animals in the experimental (n = 7, 34 motoneurons) and control (n = 7, 32 motoneurons) groups. Monosynaptic Ia excitatory postsynaptic potentials (EPSPs) were evoked by electrical stimulation of afferent fibers from the synergistic lateral gastrocnemius and soleus muscles. Data were analyzed using a mixed linear model. The central latencies of EPSPs were 0.45-0.9 ms with no differences in the mean values between the analyzed groups (P = 0.291). WBV induced an increase of the mean EPSP amplitude by 28% (P = 0.025), correlated with the resting membrane potential and input resistance, and a shortening of the mean EPSP rise time by 11% (P = 0.012). The potentiation of synaptic excitation of motoneurons was not accompanied by changes of passive membrane properties, pointing to synaptic plasticity. This indicates that WBV may support rehabilitation or training processes aimed at increasing muscle strength on the basis of increased motoneuronal drive.NEW & NOTEWORTHY The study provides new information on neuronal plasticity following repeatedly exerted mechanical loading. We demonstrate in electrophysiological experiments on rat lumbar motoneurons that low-volume whole body vibration applied systematically for 5 wk potentiates synaptic excitation from primary muscle afferents. The adaptive changes are expressed by higher amplitudes and shorter rise times of monosynaptic EPSPs evoked in motoneurons of the vibrated group compared with the control.

Effect of synchronization of firings of different motor unit types on the force variability in a model of the rat medial gastrocnemius muscle.

The synchronized firings of active motor units (MUs) increase the oscillations of muscle force, observed as physiological tremor. This study aimed to investigate the effects of synchronizing the firings within three types of MUs (slow-S, fast resistant to fatigue-FR, and fast fatigable-FF) on the muscle force production using a mathematical model of the rat medial gastrocnemius muscle. The model was designed based on the actual proportion and physiological properties of MUs and motoneurons innervating the muscle. The isometric muscle and MU forces were simulated by a model predicting non-synchronized firing of a pool of 57 MUs (including 8 S, 23 FR, and 26 FF) to ascertain a maximum excitatory signal when all MUs were recruited into the contraction. The mean firing frequency of each MU depended upon the twitch contraction time, whereas the recruitment order was determined according to increasing forces (the size principle). The synchronization of firings of individual MUs was simulated using four different modes and inducing the synchronization of firings within three time windows (± 2, ± 4, and ± 6 ms) for four different combinations of MUs. The synchronization was estimated using two parameters, the correlation coefficient and the cross-interval synchronization index. The four scenarios of synchronization increased the values of the root-mean-square, range, and maximum force in correlation with the increase of the time window. Greater synchronization index values resulted in higher root-mean-square, range, and maximum of force outcomes for all MU types as well as for the whole muscle output; however, the mean spectral frequency of the forces decreased, whereas the mean force remained nearly unchanged. The range of variability and the root-mean-square of forces were higher for fast MUs than for slow MUs; meanwhile, the relative values of these parameters were highest for slow MUs, indicating their important contribution to muscle tremor, especially during weak contractions.

Is there hope that transpinal direct current stimulation corrects motoneuron excitability and provides neuroprotection in amyotrophic lateral sclerosis?

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of largely unknown pathophysiology, characterized by the progressive loss of motoneurons (MNs). We review data showing that in presymptomatic ALS mice, MNs display reduced intrinsic excitability and impaired level of excitatory inputs. The loss of repetitive firing specifically affects the large MNs innervating fast contracting muscle fibers, which are the most vulnerable MNs in ALS. Interventions that aimed at restoring either the intrinsic excitability or the synaptic excitation result in a decrease of disease markers in MNs and delayed neuromuscular junction denervation. We then focus on trans-spinal direct current stimulation (tsDCS), a noninvasive tool, since it modulates the activity of spinal neurons and networks. Effects of tsDCS depend on the polarity of applied current. Recent work shows that anodal tsDCS induces long-lasting enhancement of MN excitability and synaptic excitation of spinal MNs. Moreover, we show preliminary results indicating that anodal tsDCS enhances the excitatory synaptic inputs to MNs in ALS mice. In conclusion, we suggest that chronic application of anodal tsDCS might be useful as a complementary method in the management of ALS patients.

Effects of an Indoor Cycling Program on Cardiometabolic Factors in Women with Obesity vs. Normal Body Weight.

The study aimed to provide evidence on the impact of indoor cycling (IC) in reducing cardiometabolic risk factors. The study compares the effects of a 3 month IC program involving three 55 min sessions per week on women aged 40-60 years, with obesity (OW, n = 18) vs. women with normal body weight (NW, n = 8). At baseline and at the end of the study, anthropometric parameters, oxygen uptake (VO2 peak), and serum parameters: glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), insulin, human anti-oxidized low-density lipoprotein antibody (OLAb), total blood antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS), endothelial nitric oxide synthase (eNOS), C-reactive protein (CRP), lipid accumulation product (LAP), and homeostasis model assessment of insulin resistance index (HOMA IR) were determined. Before the intervention, VO2 peak and HDL-C levels were significantly lower and levels of TG, LAP, insulin, HOMA-IR, and CRP were significantly higher in the OW group compared to those in the NW group. After the intervention, only the OW group saw a decrease in body mass, total cholesterol, OLAb, TBARS, and CRP concentration and an increase in total body skeletal muscle mass and HDL-C concentration. In response to the IC training, measured indicators in the OW group were seen to approach the recommended values, but all between-group differences remained significant. Our results demonstrate that IC shows promise for reducing cardiometabolic risk factors, especially dyslipidemia. After 12 weeks of regular IC, the metabolic function of the OW group adapted in many aspects to be more like that of the NW group.

Polarity-dependent adaptations of motoneuron electrophysiological properties after 5-wk transcutaneous spinal direct current stimulation in rats.

Recently, it has been shown that spinal cord polarization considerably modulates motoneuron activity, with certain observed changes in motoneuron membrane and firing properties outlasting the duration of polarization. The purpose of this study was to determine whether repeated sessions of transcutaneous transspinal direct current stimulation (tsDCS) induce adaptive changes in motoneuron properties. In this study, adult male Wistar rats under isoflurane anesthesia were subjected to anodal (n = 6) or cathodal (n = 6) tsDCS (100 µA, 15 min) 5 days per week for 5 wk. Sham control group rats (n = 6) served as a reference. Intracellular recordings from lumbar spinal motoneurons were performed under pentobarbital anesthesia 1 day after the final tsDCS session to analyze membrane and firing properties. Anodal polarization appeared to be effective in evoking significant adaptive changes toward the facilitation of motoneuron firing. When compared with the sham polarization group, these adaptations were expressed by the increased input resistance (P = 0.0077), decreased voltage threshold for spike generation (P = 0.0248) and doublet threshold (P = 0.0311), and increased maximum steady-state firing (SSF) frequency (P = 0.0073), SSF frequency range (P = 0.0075) and slope of the frequency-current relationship (P = 0.0111). However, the effects of cathodal polarization were modest and generally not significant in regard to the sham control. These novel findings support the existing knowledge on alterations in spinal neuronal network excitability in response to polarization and provide the direct evidence of adaptive neuroplasticity of spinal motoneurons in response to chronically applied tsDCS.NEW & NOTEWORTHY Transcutaneous spinal direct current stimulation applied systematically for 5 wk evoked polarity-dependent adaptations in the electrophysiological properties of rat spinal motoneurons. After anodal polarization sessions, motoneurons became more excitable and could evoke higher maximum discharge frequencies during repetitive firing than motoneurons in the sham polarization group. However, no significant adaptive changes of motoneuron properties were observed after repeated cathodal polarization in comparison with the sham control group.

Sex Differences in Maintaining the Requested Handgrip Force Enhanced by Auditory or Visual Feedback.

Thus far, the differences in effect of auditory or visual feedback in motor learning have presented results derived from mixed groups and sex differences have not been considered. However, perception and processing of auditory stimuli and performance of visual motor tasks appear to be sex-related. The purpose of this study was to investigate the learning of the simple motor task of maintaining a requested handgrip force in separate male and female groups. A total of 31 volunteers (15 males, 16 females) were randomly assigned to one of four experimental groups with defined sex and training conditions (audio or visual feedback). Participants performed training sessions over a period of six days, for which auditory or visual feedback was provided, and the effectiveness of both types of signals was compared. The evident learning effect was found in all groups, and the main effect of sex was significant among visual groups in favor of the males (p < 0.05). On the other hand, the main effect of feedback conditions was found to be significant among females, beneficially in the case of auditory displays (p < 0.05). The results lead to the conclusion that an equal number of males and females in mixed experimental groups may be supportive to obtain reliable results. Moreover, in motor-learning studies conducted on females only, a design including auditory feedback would be more suitable.

In Vivo Intracellular Recording of Type-Identified Rat Spinal Motoneurons During Trans-Spinal Direct Current Stimulation.

Intracellular recording of spinal motoneurons in vivo provides a "gold standard" for determining the cells' electrophysiological characteristics in the intact spinal network and holds significant advantages relative to classical in vitro or extracellular recording techniques. An advantage of in vivo intracellular recordings is that this method can be performed on adult animals with a fully mature nervous system, and therefore many observed physiological mechanisms can be translated to practical applications. In this methodological paper, we describe this procedure combined with externally applied constant current stimulation, which mimics polarization processes occurring within spinal neuronal networks. Trans-spinal direct current stimulation (tsDCS) is an innovative method increasingly used as a neuromodulatory intervention in rehabilitation after various neurological injuries as well as in sports. The influence of tsDCS on the nervous system remains poorly understood and the physiological mechanisms behind its actions are largely unknown. The application of the tsDCS simultaneously with intracellular recordings enables us to directly observe changes of motoneuron membrane properties and characteristics of rhythmic firing in response to the polarization of the spinal neuronal network, which is crucial for the understanding of tsDCS actions. Moreover, when the presented protocol includes the identification of the motoneuron with respect to an innervated muscle and its function (flexor versus extensor) as well as the physiological type (fast versus slow) it provides an opportunity to selectively investigate the influence of tsDCS on identified components of spinal circuitry, which seem to be differently affected by polarization. The presented procedure focuses on surgical preparation for intracellular recordings and stimulation with an emphasis on the steps which are necessary to achieve preparation stability and reproducibility of results. The details of the methodology of the anodal or cathodal tsDCS application are discussed while paying attention to practical and safety issues.

Long-lasting modifications of motoneuron firing properties by trans-spinal direct current stimulation in rats.

Trans-spinal direct current stimulation (tsDCS) is a novel neuromodulatory technique that has been used during neurological rehabilitation and sports to modulate muscle activation. However, the physiological mechanisms that underly the long-lasting functional effects of polarization are not yet fully understood, nor are their relationships with specific neuronal populations. The acute facilitatory and depressive effects of anodal and cathodal polarization on motoneurons have been recently demonstrated, and the aim of this study was to determine whether tsDCS-evoked modulations of motoneuron properties are able to persist over several hours. Intracellular recordings from multiple antidromically identified rat motoneurons were performed both before and after the application of tsDCS (0.1 mA for 15 min), at various time points up to 180 min after the offset of anodal or cathodal tsDCS. The examined effects of anodal polarization included decreased rheobase, voltage threshold, the minimum and maximum currents necessary for rhythmic firing, increased rhythmic firing frequencies and the slope of the f-I relationship. The majority of these facilitatory changes to threshold and firing properties were sustained for 30-60 min after polarization. In contrast, the significant effects of cathodal polarization were absent, except the short-lasting decreased ability for motoneurons to induce rhythmic activity. This study provides direct evidence that a single polarization session can alter the electrophysiological properties of motoneurons for at least one hour and provides a basis for the further use of tsDCS techniques under conditions where the sustained modification of motoneuron firing is desired.

Adaptation of motor unit contractile properties in rat medial gastrocnemius to treadmill endurance training: Relationship to muscle mitochondrial biogenesis.

This study aimed at investigating the effects of 2, 4 and 8 weeks of endurance training on the contractile properties of slow (S), fast fatigue resistant (FR) and fast fatigable (FF) motor units (MUs) in rat medial gastrocnemius (MG) in relation to the changes in muscle mitochondrial biogenesis. The properties of functionally isolated MUs were examined in vivo. Mitochondrial biogenesis was judged based on the changes in mitochondrial DNA copy number (mtDNA), the content of the electron transport chain (ETC) proteins and PGC-1α in the MG. Moreover, the markers of mitochondria remodeling mitofusins (Mfn1, Mfn2) and dynamin-like protein (Opa1) were studied using qPCR. A proportion of FR MUs increased from 37.9% to 50.8% and a proportion of FF units decreased from 44.7% to 26.6% after 8 weeks of training. The increased fatigue resistance, shortened twitch duration, and increased ability to potentiate force were found as early as after 2 weeks of endurance training, predominantly in FR MUs. Moreover, just after 2 weeks of the training an enhancement of the mitochondrial network remodeling was present as judged by an increase in expression of Mfn1, Opa1 and an increase in PGC-1α in the slow part of MG. Interestingly, no signs of intensification of mitochondrial biogenesis assessed by ETC proteins content and mtDNA in slow and fast parts of gastrocnemius were found at this stage of the training. Nevertheless, after 8 weeks of training an increase in the ETC protein content was observed, but mainly in the slow part of gastrocnemius. Concluding, the functional changes in MUs' contractile properties leading to the enhancement of muscle performance accompanied by an activation of signalling that controls the muscle mitochondrial network reorganisation and mitochondrial biogenesis belong to an early muscle adaptive responses that precede an increase in mitochondrial ETC protein content.

Adaptations of motoneuron properties after weight-lifting training in rats.

Resistance training, with repeated short-term and high-intensity exercises, is responsible for an increase in muscle mass and force. The aim of this study was to determine whether such training induces adaptations in the electrophysiological properties of motoneurons innervating the trained muscles and to relate these adaptive changes to previous observations made on motor unit contractile properties. The study was performed on adult male Wistar rats. Animals from the training group were subjected to a 5-wk voluntary progressive weight-lifting program, whereas control rats were restricted to standard cage activity. Intracellular recordings from lumbar spinal motoneurons were made under pentobarbital anesthesia. Membrane properties were measured, and rhythmic firing of motoneurons was analyzed. Strength training evoked adaptive changes in both slow- and fast-type motoneurons, indicating their increased excitability. A shorter spike duration, a higher input resistance, a lower rheobase, a decrease in the minimum current required to evoke rhythmic firing, an increase in the maximum frequencies of the early-state firing (ESF) and the steady-state firing (SSF), and an increase in the respective slopes of the frequency-current (f/I) relationship were observed in fast motoneurons of the trained group. The increase in the maximum ESF and SSF frequencies and an increase in the SSF f/I slope were also present in slow motoneurons. Higher maximum firing rates of motoneurons as well as higher discharge frequencies evoked at the same level of intracellular depolarization current imply higher levels of tetanic forces developed by motor units over the operating range of force production after strength training.NEW & NOTEWORTHY Neuronal responses to weight-lifting training can be observed in altered properties of both slow and fast motoneurons. Motoneurons of trained animals are more excitable, require lower intracellular currents to evoke rhythmic firing, and have the ability to evoke higher maximum discharge frequencies during repetitive firing.

A General Mathematical Algorithm for Predicting the Course of Unfused Tetanic Contractions of Motor Units in Rat Muscle.

An unfused tetanus of a motor unit (MU) evoked by a train of pulses at variable interpulse intervals is the sum of non-equal twitch-like responses to these stimuli. A tool for a precise prediction of these successive contractions for MUs of different physiological types with different contractile properties is crucial for modeling the whole muscle behavior during various types of activity. The aim of this paper is to develop such a general mathematical algorithm for the MUs of the medial gastrocnemius muscle of rats. For this purpose, tetanic curves recorded for 30 MUs (10 slow, 10 fast fatigue-resistant and 10 fast fatigable) were mathematically decomposed into twitch-like contractions. Each contraction was modeled by the previously proposed 6-parameter analytical function, and the analysis of these six parameters allowed us to develop a prediction algorithm based on the following input data: parameters of the initial twitch, the maximum force of a MU and the series of pulses. Linear relationship was found between the normalized amplitudes of the successive contractions and the remainder between the actual force levels at which the contraction started and the maximum tetanic force. The normalization was made according to the amplitude of the first decomposed twitch. However, the respective approximation lines had different specific angles with respect to the ordinate. These angles had different and non-overlapping ranges for slow and fast MUs. A sensitivity analysis concerning this slope was performed and the dependence between the angles and the maximal fused tetanic force normalized to the amplitude of the first contraction was approximated by a power function. The normalized MU contraction and half-relaxation times were approximated by linear functions depending on the normalized actual force levels at which each contraction starts. The normalization was made according to the contraction time of the first contraction. The actual force levels were calculated initially from the recorded tetanic curves and subsequently from the modeled curves obtained from the summation of all models of the preceding contractions (the so called "full prediction"). The preciseness of the prediction was verified by two coefficients estimating the error between the modeled and the experimentally recorded curves. The proposed approach was tested for 30 MUs from the database and for three additional MUs, not included in the initial set. It was concluded that this general algorithm can be successfully used for modeling of a unfused tetanus course of a single MU of fast and slow type.

Prolonged activity evokes potentiation and the "sag" phenomenon in slow motor units of rat soleus.

Slow motor units (MUs) have no sag in their unfused tetani. This study in anesthetized rats shows that the sag can be observed in slow soleus MUs after prolonged activity. Twitches and unfused tetanic contractions were recorded from male (n=35) and female (n=39) MUs before and after the four minutes of the fatigue test (trains of 13 pulses at 40 Hz repeated every second). After this activity twitch contractions potentiated and a shift in the steep part of the force-frequency curve towards lower frequencies was observed in both sexes. Initially no sag was visible in unfused tetani, but after the fatigue test the phenomenon was observed in 77% of male, while in 13% of female MUs, the result consistent with the previously reported higher content of IIa myosin and faster contraction of MUs in male soleus. The decomposition of tetani with sag into trains of twitch-shape responses to consecutive stimuli revealed higher forces of initial decomposed twitches than later. The revealed alterations the force development due to long-lasting activation of slow MUs were sex-related and more pronounced in male soleus.

Summation of slow motor unit forces at constant and variable interpulse intervals in rat soleus muscle.

Effects of the summation of forces generated by functionally isolated slow-twitch motor units (MU) of the rat soleus muscle were examined in this study. Initially, the twitch, fused tetanic and unfused tetanic contractions evoked by trains of stimuli at variable interpulse intervals were recorded for each MU. Then, two, three or four MUs were co-activated, and the recorded forces were compared to the algebraic sum of the forces of individual MUs. The mean cumulative force of twitches and the mean cumulative force of fused tetani were not statistically different from the respective algebraic sums of forces, which revealed a high degree of linearity in the summation. However, relaxation of the recorded tetanic contractions (either fused or unfused) was faster than that predicted by the linear summation of individual contractions. Moreover, for twitch and tetanic contractions, a tendency to shorten relaxation with an increasing number of co-active MUs was noted. The results indicate that forces of rat soleus slow MUs sum up more linearly than in the respective cat muscle as well as more linearly than for fast MUs in the medial gastrocnemius muscle.

Force regulation and electrical properties of motor units in overloaded muscle.

INTRODUCTION: The influence of long-term muscle overload on force regulation and electrical properties of motor units (MUs) was investigated in rats. METHODS: Compensatory overload of the medial gastrocnemius was induced by tenotomy of its synergists. Electrophysiological experiments were performed on functionally isolated MUs 3 months after the surgery. RESULTS: Force-frequency curves for overloaded MUs were shifted rightward compared with control, thus MUs developed the same relative tetanic forces at higher frequencies. Higher force increase was achieved in response to an increase in stimulation frequency in overloaded fast MUs compared with control. The optimal tetanic contraction, characterized by the highest force-time area per pulse, was evoked at higher stimulation frequencies for all overloaded MUs except FF. Only minor adaptive changes in MU action potentials occurred. CONCLUSIONS: Compensatory muscle overload leads to substantial modifications in MU force development mechanisms, which are MU-type-specific and influence whole muscle force regulation.