Minor effect of loss to follow-up on outcome interpretation in the Swedish spine register.

BACKGROUND AND PURPOSE: Loss to follow-up in observational studies may skew results and hamper study reliability. We evaluated the importance of loss to follow-up in the Swedish spine register. PATIENTS: Patients operated in the lumbar spine and scheduled for a postal questionnaire follow-up during part of 2016 were identified. Out of the 351 patients, 203 had responded. After multiple attempts, 115 of the 148 non-responders were reached; 68 returned the complete questionnaire; and 47 answered a brief questionnaire by phone. Analyses were made with the Chi-square test, analysis of covariance or logistic regression. Some analyses were adjusted. RESULTS: At baseline, the non-responders were younger than the responders (55 vs 61 years, p < 0.001) and had higher Oswestry Disability Index (ODI) (54 vs 48, p = 0.003), lower SF-36 physical component summary score (PCS) (36 vs 40, p = 0.011) and lower EQ-5D (0.17 vs 0.27, p = 0.018). Mean back pain, leg pain, ODI, EQ-5D, SF-36 mental component summary score (MCS) improved significantly in both groups (all p < 0.001). SF-36 PCS did not improve in the non-responder group (p = 0.063). Non-responders perceived less improvement in back pain (global assessment back 60% vs 72%, p = 0.002). At follow-up, there were no differences in patient-reported outcome measures between the groups (all p ≥ 0.06), with the exception of a lower SF-36 MCS among the non-responders (p = 0.015). INTERPRETATION: After surgery for lumbar spine degenerative disorders, non-responders achieve similar outcome as responders in the Swedish spine register, with the exception of a lower mental health and less perceived improvement in back pain. These slides can be retrieved under Electronic Supplementary Material.

Jaw-opening accuracy is not affected by masseter muscle vibration in healthy men.

There is a functional integration between the jaw and neck regions with head extension-flexion movements during jaw-opening/closing tasks. We recently reported that trigeminal nociceptive input by injection of hypertonic saline into the masseter muscle altered this integrated jaw-neck function during jaw-opening/closing tasks. Thus, in jaw-opening to a predefined position, the head-neck component increased during pain. Previous studies have indicated that muscle spindle stimulation by vibration of the masseter muscle may influence jaw movement amplitudes, but the possible effect on the integrated jaw-neck function is unknown. The aim of this study was to investigate the effect of masseter muscle vibration on jaw-head movements during a continuous jaw-opening/closing task to a target position. Sixteen healthy men performed two trials without vibration (Control) and two trials with bilateral masseter muscle vibration (Vibration). Movements of the mandible and the head were registered with a wireless three-dimensional optoelectronic recording system. Differences in jaw-opening and head movement amplitudes between Control and Vibration, as well as achievement of the predefined jaw-opening target position, were analysed with Wilcoxon's matched pairs test. No significant group effects from vibration were found for jaw or head movement amplitudes, or in the achievement of the target jaw-opening position. A covariation between the jaw and head movement amplitudes was observed. The results imply a high stability for the jaw motor system in a target jaw-opening task and that this task was achieved with the head-neck and jaw working as an integrated system.

Comparative metabolomics of muscle interstitium fluid in human trapezius myalgia: an in vivo microdialysis study.

PURPOSE: The mechanisms behind trapezius myalgia are unclear. Many hypotheses have been presented suggesting an altered metabolism in the muscle. Here, muscle microdialysate from healthy and myalgic muscle is analysed using metabolomics. Metabolomics analyse a vast number of metabolites, enabling a comprehensive explorative screening of the cellular processes in the muscle. METHODS: Microdialysate samples were obtained from the shoulder muscle of healthy and myalgic subjects that performed a work and stress test. Samples from the baseline period and from the recovery period were analysed using gas chromatography­mass spectrometry (GC­MS) together with multivariate analysis to detect differences in extracellular content of metabolites between groups. Systematic differences in metabolites between groups were identified using multivariate analysis and orthogonal partial least square discriminate analysis (OPLS-DA). A complementary Mann­Whitney U test of group difference in individual metabolites was also performed. RESULTS: A large number of metabolites were detected and identified in this screening study. At baseline, no systematic differences between groups were observed according to the OPLS-DA. However, two metabolites, l-leucine and pyroglutamic acid, were significantly more abundant in the myalgic muscle compared to the healthy muscle. In the recovery period, systematic difference in metabolites between the groups was observed according to the OPLS-DA. The groups differed in amino acids, fatty acids and carbohydrates. Myristic acid and putrescine were significantly more abundant and beta-d-glucopyranose was significantly less abundant in the myalgic muscle. CONCLUSION: This study provides important information regarding the metabolite content, thereby presenting new clues regarding the pathophysiology of the myalgic muscle.

Systemic differences in serum metabolome: a cross sectional comparison of women with localised and widespread pain and controls.

Chronic musculoskeletal pain exists either as localised to a single region or as widespread to multiple sites in several quadrants of the body. Prospective studies indicate that widespread pain could act as a far end of a continuum of musculoskeletal pain that started with chronic localised pain. The mechanism by which the transition from localised pain to widespread occurs is not clear, although many studies suggest it to be an altered metabolism. In this study, systemic metabolic differences between women with chronic localised neck-shoulder pain (NP), women with chronic widespread pain (CWP) and women who were healthy (CON) were assessed. Blood samples were analysed taking a metabolomics approach using gas chromatography mass spectrometry (GC-MS) and orthogonal partial least square discriminant analysis (OPLS-DA). The metabolomics analysis showed a clear systematic difference in the metabolic profiles between the subjects with NP and the CON but only a weak systematic difference between the subjects with CWP and the CON. This most likely reflects a difference in the portion of the metabolome influenced by the two pain conditions. In the NP group, the overall metabolic profile suggests that processes related to energy utilisation and lipid metabolism could be central aspects of mechanisms maintaining disorder.

Influences on the fusimotor-muscle spindle system from chemosensitive nerve endings in cervical facet joints in the cat: possible implications for whiplash induced disorders.

The aim of the present study was to establish if there exists reflex connections from ligamentous structures in cervical facet joints and the fusimotor system of dorsal neck muscles. In seven cats, anaesthetized with alpha-chloralose, bradykinin (BK) of concentrations between 12 and 50 microg was injected into the facet joint between C1 and C2. Recordings were made from single muscle spindle afferents (MSA) originating in contralateral trapezius and splenius muscles (TrSp). Fusimotor induced changes in the sensitivity of the muscle spindle afferents were assessed by recording the responses to sinusoidal stretches of the TrSp muscles. The mean rate of discharge and the depth of modulation of a fitted sine were taken as quantitative estimates of the response. A total of 25 MSAs were recorded, and 21 of these showed clear-cut alterations in their responses to the sinusoidal stretches following Bk. injections into contralateral facet joint. The majority of the responding afferents (13/21) showed changes in their responses indicating an increased activity of static fusimotoneurones, although responses of dynamic and mixed static and dynamic nature were also seen. Local anaesthetics applied to the intraarticular receptors abolished the effects. Injection (i.v.) of a general anaesthetic (pentobarbital) abolished the effects. The results show that there exist reflex connections between receptors in cervical facet joints and fusimotoneurones of dorsal neck muscles, and this might be of importance in the pathophysiology behind whiplash associated disorders (WAD).

Fatigue effects in the cat gastrocnemius during frequency-modulated efferent stimulation.

Effects of low- and high-frequency fatigue were studied on muscle dynamics in isometric conditions of the cat gastrocnemius. Fatiguing sessions consisted of 25-28 repetitions of the standard tests that included an 18-s interval of continuous frequency-modulated stimulation preceded and followed by single stimuli evoking twitch contractions. The rate of the continuous part was changed in accordance with a symmetrical double-trapezoidal signal, including three successive phases of constant rate at 10, 40 and 10s(-1); between these phases, each lasting for 4s, the rate changed linearly within a 2-s interval. The following modes of muscle activation were applied: (i) stimulation of single filaments constituting approximately one-fifth to one-seventh of the total cross-section of the L(7) and S(1) ventral roots; (ii) the distributed stimulation of five similar filaments; and (iii) direct stimulation of muscle through bipolar wire electrodes. A relative drop in tension, the fatigue index, expressed as the ratio at the end of a fatigue session over its value at the beginning of the test, was used to quantify fatigue effects. The fatigue indices during low-rate stimulation were 0.56+/-0.03 (mean+/-S.D.) at the first phase and 0. 64+/-0.02 at the third phase, while during high-rate stimulation this parameter was only 0.32+/-0.02. The high-rate stimulation noticeably increased the mean tension during low-rate stimulation; the ratio between the reactions at the third and the first phases could be as much as two to three times greater than that at the beginning of the fatigue session. It was demonstrated that the potentiation was connected with after-effects of the rate-tension hysteresis. The hysteresis decreased with fatigue, the fatigue index for the rate-tension loop areas ranging from 0.39 to 0.52 (0.45+/-0. 05, mean+/-S.D.). The fatigue processes developed more quickly and intensively in the previously fatigued muscles: the obtained fatigue indices were 0.73+/-0.05 and 0.70+/-0.10 at the first and third phases, and 0.62+/-0.06 (mean+/-S.D.) at the second phase of stimulation, respectively. In the cases of distributed and direct stimulation applied to muscles in a fresh state, fatigue dynamics did not differ significantly from those observed during single-filament stimulation. In experiments with distributed stimulation applied to previously fatigued muscles, a powerful depression of the high-rate components was registered in several cases, which seemed to be connected with depressive effects at the level of nerve-muscle synaptic transmission. The effects of low- and high-frequency fatigue were studied in isometric conditions of muscle contraction. In addition to the well-known differentiation between low- and high-frequency fatigue effects, the complex pattern of efferent stimulation used allowed us to identify additional fatigue-related changes in the rate-tension hysteresis. This hysteresis seems to be one of the possible mechanisms directed to compensate for low-frequency fatigue in the muscle contraction.

Fatigue-related changes in electomyogram activity of the cat gastrocnemius during frequency-modulated efferent stimulation.

Changes in the compound muscle action potentials of cat gastrocnemius muscle were studied during low- and high-frequency fatigue. Fatiguing session consisted of 25-28 repetitions of the standard single fatigue tests (1.5min interval between the tests) that included the part of continuous frequency-modulated stimulation preceded and followed by single stimuli evoking twitch contractions in the muscle. The rate of the continuous part was changed in accordance with symmetrical double-trapezoidal signal, including three successive phases of constant rate at 10, 40 and 10s(-1); between these phases of 4s duration the rate changed linearly within a 2s interval. During fatigue relative changes in compound muscle action potential waves were usually smaller than changes in tension. Within the same fatigue procedure applied to a fresh muscle, the drop in tension was as much as 35% for high-rate stimulation and 59-71% for low-rate stimulation, whereas the decrease of the peak-to-peak compound muscle action potential waves amplitudes did not exceed 10-20%. Compound muscle action potential waves underwent the most pronounced depression during high-rate stimulation, the decrease proceeding during the following phase of low-rate stimulation. The tension changes during long-lasting activation were different for low- and high-frequency fatigue, with more pronounced depression during low-rate stimulation. As a rule, compound muscle action potential waves changes followed opposite patterns. Compound muscle action potential waves progressively split up, which was probably associated with a continuous slowing of the action potentials in the most fatigable motor units and the subsequent disappearance of the reactions at least in part of the motor units. Hysteresis effects in muscle contraction seem to be able, at least in part, to compensate for some of the depressive effects appearing during conduction of action potentials in muscle fibres. Changes in the compound muscle action potentials were studied during development of the muscle fatigue. These changes showed pronounced dependency on stimulation rate allowing differentiating effects of low- and high-frequency stimulation of the efferents supplying muscle under study. At the same time the fatigue-related changes in the action potentials were noticeably smaller than changes in tension, thus supporting existing concepts in the field arguing that fatigue effects are mainly connected with corresponding activity-dependent changes in muscle contraction machinery.

A technique for estimating activity in whole nerve trunks applied to the cervical sympathetic trunk, in the rabbit.

The changes in sympathetic outflow may be evaluated from the amplitude of the antidromic compound action potential (ACAP) according to the collision technique described by Douglas and Ritchie (Douglas, W.W. and Ritchie J.M., A technique for recording functional activity in specific groups of medullated and non-medullated fibers in whole nerve trunks. J. Physiol., 138(1957) 19-30). This technique was revised, taking into account the depressant action exerted by antidromic stimulation on sympathetic preganglionic neurones (SPNs). Cervical sympathetic nerve (CSN) of rabbits was used as experimental model. Stimulation frequencies of 0.2-0.5 Hz were found to be sufficiently low to avoid depressant actions on CSN spontaneous activity; they were employed to test the sensitivity of the technique during different experimental manoeuvres, such as changes in pulmonary-ventilation, baroreceptor unloading and arousal stimuli. In addition a procedure was devised to calibrate the ACAP amplitude: high frequency antidromic stimulation was used to induce a complete and transient inhibition of SPNs which allows to record the ACAP maximum amplitude. ACAPs recorded in various experimental conditions can then be expressed as percentage of this value.

Elevated intramuscular concentration of bradykinin in jaw muscle increases the fusimotor drive to neck muscles in the cat.

Patients suffering from temporomandibular dysfunction exhibit clinical findings such as fatigue, painful muscles, and muscles that are tender to palpation, not only in the temporomandibular area, but also in the neck/shoulder region. The mechanisms behind this are not known, although previous studies of similar spreading phenomena have revealed a possible involvement of the fusimotor system. In the present study, we evaluated the activity of this system by recording the activity of muscle spindle afferents from dorsal neck muscles after intramuscular injections of 6 microg to 25 microg bradykinin in the ipsilateral masseter muscle. A total of 23 muscle spindle afferents from the trapezius and splenius muscles was recorded at the C3-C4 level in 7 adult cats anesthetized with alpha-chloralose. Of these 23 afferents, 17 (74%) showed significantly different responses to bradykinin injections compared with control injections (dissolving agent, Tyrode), and the majority of the effects were compatible with an increased static fusimotor drive to the muscle spindle system. Thus, the results demonstrate potent reflex connections from groups III and IV masseter muscle afferents to fusimotor neurones on the C3-C4 level. It is concluded that the fusimotor system might play a significant role in the mechanisms behind the spread of muscle pain and tension from the temporomandibular region to the neck.

Localized muscle fatigue decreases the acuity of the movement sense in the human shoulder.

PURPOSE: The purpose of this study was to investigate alterations in the movement sense acuity during localized muscle fatigue in the human dominant shoulder. METHODS: Fourteen healthy volunteers (8 males and 6 females) with a mean age 23 +/- 2 yr participated in the study. The subjects' ability to discriminate movement velocity relative to a reference velocity imposed over the dominant shoulder was tested following two experimental conditions: 1) Light exercise (LE), repetitive isokinetic horizontal flexion/extensions at the shoulder, ranging from 85 degrees to 20 degrees relative to the frontal plane, at 10% of maximal voluntary contraction (MVC) and 2) Hard exercise (HE), same movements as in LE, but performing MVC to fatigue. RESULTS: The results showed that subjects had a lower probability of distinguishing between different movement velocities following HE as compared with those during the LE condition (P < 0.001). When genders were compared, female subjects had a lower probability of distinguishing correctly than male subjects (P < 0.001). CONCLUSIONS: The acuity of the movement sense in the dominant shoulder is reduced in the presence of shoulder muscle fatigue. The possible influence of muscle fatigue via peripheral muscle receptors on movement sense is discussed.

Experimental masseter muscle pain alters jaw-neck motor strategy.

BACKGROUND: A functional integration between the jaw and neck regions has been demonstrated during normal jaw function. The effect of masseter muscle pain on this integrated motor behaviour in man is unknown. The aim of this study was to investigate the effect of induced masseter muscle pain on jaw-neck movements during a continuous jaw opening-closing task. METHODS: Sixteen healthy men performed continuous jaw opening-closing movements to a target position, defined as 75% of the maximum jaw opening. Each subject performed two trials without pain (controls) and two trials with masseter muscle pain, induced with hypertonic saline as a single injection. Simultaneous movements of the mandible and the head were registered with a wireless optoelectronic three-dimensional recording system. Differences in movement amplitudes between trials were analysed with Friedman's test and corrected Wilcoxon matched pairs test. RESULTS: The head movement amplitudes were significantly larger during masseter muscle pain trials compared with control. Jaw movement amplitudes did not differ significantly between any of the trials after corrected Wilcoxon tests. The ratio between head and jaw movement amplitudes was significantly larger during the first pain trial compared with control. CONCLUSIONS: Experimental masseter muscle pain in humans affected integrated jaw-neck movements by increasing the neck component during continuous jaw opening-closing tasks. The findings indicate that pain can alter the strategy for jaw-neck motor control, which further underlines the functional integration between the jaw and neck regions. This altered strategy may have consequences for development of musculoskeletal pain in the jaw and neck regions.

Effects of 30 versus 60 min of low-load work on intramuscular lactate, pyruvate, glutamate, prostaglandin E(2) and oxygenation in the trapezius muscle of healthy females.

The aim of this study was to investigate the effects of duration of low-load repetitive work on intramuscular lactate, pyruvate, glutamate and prostaglandin E(2) (PGE(2)), and oxygen saturation in the trapezius muscle. Twenty healthy females were studied during baseline rest, during low-load repetitive work for either 30 (REP 30) or 60 min (REP 60) and 60 min recovery. Intramuscular microdialysate (IMMD) samples were obtained, and local muscle tissue oxygenation (%StO(2)) assessed with near-infrared spectroscopy (NIRS). Subjects rated their perceived exertion (Borg CR-10 scale) and capillary blood was sampled for lactate analysis. The results showed a significant increase in IMMD lactate in response to both REP 30 and REP 60 (P < 0.05 and P < 0.01, respectively) and glutamate (P < 0.0001), but no progressive increase with increasing work duration. Both IMMD pyruvate and lactate tended to be significantly increased during the recovery period. No corresponding increase in blood lactate was found. Local muscle %StO(2) did not change significantly in response to work and was not correlated to the IMMD lactate concentration. The ratings of perceived exertion increased in response to work, and remained increased after recovery for REP 60. In conclusion, the results of this study show significantly increased IMMD lactate and, glutamate concentrations in the trapezius muscle of healthy females in response to low-load work, but no progressive increase with increased work duration. Further, they do not indicate that the increased IMMD lactate concentration was caused by a locally decreased or insufficient muscle tissue oxygenation.

Responses of muscle spindles in feline dorsal neck muscles to electrical stimulation of the cervical sympathetic nerve.

Previous studies performed in jaw muscles of rabbits and rats have demonstrated that sympathetic outflow may affect the activity of muscle spindle afferents (MSAs). The resulting impairment of MSA information has been suggested to be involved in the genesis and spread of chronic muscle pain. The present study was designed to investigate sympathetic influences on muscle spindles in feline trapezius and splenius muscles (TrSp), as these muscles are commonly affected by chronic pain in humans. Experiments were carried out in cats anesthetized with alpha-chloralose. The effect of electrical stimulation (10 Hz for 90 s or 3 Hz for 5 min) of the peripheral stump of the cervical sympathetic nerve (CSN) was investigated on the discharge of TrSp MSAs (units classified as Ia-like and II-like) and on their responses to sinusoidal stretching of these muscles. In some of the experiments, the local microcirculation of the muscles was monitored by laser Doppler flowmetry. In total, 46 MSAs were recorded. Stimulation of the CSN at 10 Hz powerfully depressed the mean discharge rate of the majority of the tested MSAs (73%) and also affected the sensitivity of MSAs to sinusoidal changes of muscle length, which were evaluated in terms of amplitude and phase of the sinusoidal fitting of unitary activity. The amplitude was significantly reduced in Ia-like units and variably affected in II-like units, while in general the phase was affected little and not changed significantly in either group. The discharge of a smaller percentage of tested units was also modulated by 3-Hz CSN stimulation. Blockade of the neuromuscular junctions by pancuronium did not induce any changes in MSA responses to CSN stimulation, showing that these responses were not secondary to changes in extrafusal or fusimotor activity. Further data showed that the sympathetically induced modulation of MSA discharge was not secondary to the concomitant reduction of muscle blood flow induced by the stimulation. Hence, changes in sympathetic outflow can modulate the afferent signals from muscle spindles through an action exerted directly on the spindles, independent of changes in blood flow. It is suggested that such an action may be one of the mechanisms mediating the onset of chronic muscle pain in these muscles in humans.

Effects of time pressure and precision demands during computer mouse work on muscle oxygenation and position sense.

The present study investigated the effects of time pressure and precision demands during computer mouse work on muscle oxygenation and position sense in the upper extremity. Twenty-four healthy subjects (12 males and 12 females) performed a 45-min standardized mouse-operated computer task on two occasions. The task consisted of painting rectangles that were presented on the screen. On one occasion, time pressure and precision demands were imposed (more demanding task, MDT), whereas, on the other occasion, no such restraints were added (less demanding task, LDT). The order of the two task versions was randomized. Tissue oxygen saturation in the trapezius and extensor carpi radialis muscles was recorded throughout, and the position-matching ability of the wrist was measured before and after the tasks. In addition, measurements of autonomic nervous system reactivity and subjective ratings of tenseness and physical fatigue were obtained. Performance was measured in terms of the number of rectangles that were painted during the task. During MDT, oxygen saturation in extensor carpi radialis decreased (P < 0.05) compared to LDT. These data were paralleled by increased electrodermal activity (P < 0.05), skin blood flow (P < 0.05), ratings of tenseness and fatigue (P < 0.01), and increased performance (P < 0.01) during MDT. Females exhibited lower oxygen saturation than males, during rest as well as during the computer tasks (P < 0.01). Wrist repositioning error increased following LDT as compared to MDT (P < 0.05). In conclusion, computer mouse work under time pressure and precision demands caused a decrease in forearm muscle oxygenation, but did not affect wrist position sense accuracy. We attribute our changes in oxygenation more to increased oxygen consumption as a result of enhanced performance, than to vasoconstriction.

Folic acid blinded trial in identical twins with fragile X syndrome.

Monozygous twin 14-year-old mentally retarded boys with the fragile X syndrome were treated either with 10 mg folic acid by mouth daily or with a placebo for three test periods of 3-month duration each in a blind study. For each twin, tests of cognitive functioning, reading, spelling, and math skills, and linguistic and perceptual skills were compared. Although there was considerable variation in performance on these tests during the two baseline periods, there were no observable beneficial effects of therapy. The routine use of folic acid in patients with established mental retardation and the fragile X syndrome is not indicated.