phosphocreatine and Pain

The presence of abnormalities in fibromyalgia muscle using current methodological approaches is well established. The more serious abnormalities are demonstrated by histologic studies particularly on electron microscopy: disorganisation of Z bands and abnormalities in the number and shape of mitochondria. Biochemical studies and P 31 magnetic resonance spectroscopy show inconstant abnormalities of ATP and phosphocreatine levels. Mitochondrial abnormalities reduced capillary circulation and thickened capillary endothelium may result in decreased availability of oxygen and impaired oxidative phosphorylation as well as ATP synthesis. These abnormalities do not seem to be the consequences of the much-discussed deconditioning of muscles although these consequences are not well known. Further studies of energy metabolism of the muscle during exercise are needed.

Topics: Adenosine Triphosphate; Endothelium, Vascular; Energy Metabolism; Fibromyalgia; Humans; Microcirculation; Microscopy, Electron; Mitochondria, Muscle; Muscle, Skeletal; Muscular Diseases; Pain; Phosphocreatine

Widespread muscle pain and tender points are the most common complaints of fibromyalgia patients, and the underlying mechanisms responsible for these symptoms have been studied intensively during the past decade. It has been suggested that fatigue and pain may lead to decreased levels of physical activity in many patients. The resulting deconditioned state may itself contribute to muscle abnormalities. Associated symptoms such as disturbed sleep, anxiety, depression, or irritable bowel also may have a negative impact on muscle function and level of daily activities. The important interactions between the central nervous and musculoskeletal systems may involve another element, the neuroendocrine stress-response system. This review will consider both the current state of knowledge and also future studies which might be designed to answer more effectively the outstanding questions regarding the underlying pathogenesis of fibromyalgia.

Topics: Adenosine Triphosphate; Biomechanical Phenomena; Energy Metabolism; Fibromyalgia; Humans; Models, Biological; Muscle, Skeletal; Musculoskeletal Diseases; Pain; Phosphocreatine; Physical Endurance

In Sweden, several studies have been performed in patients with fibromyalgia to study muscle morphology, chemistry and physiology in order to understand the origin of the most prominent symptoms in fibromyalgia: muscle pain, muscle fatigue and muscle stiffness. These studies have shown changes indicating disturbed microcirculation, mitochondrial damage and a reduced content of high energy phosphates. Thus, there may be an energy deficiency state in the resting painful muscle in fibromyalgia. Pain analysis has supported the idea that there is a nociceptive origin of the pain. Our hypothesis is that any condition that could lead to constant muscle hypoxia, e.g., through establishment of abnormal motor patterns, might be a possible cause of fibromyalgic pain.

Topics: Adenosine Triphosphate; Biopsy; Connective Tissue; Fibromyalgia; Humans; Microcirculation; Models, Biological; Muscles; Pain; Pain Measurement; Phosphocreatine

Although non-specific pain in the upper limb muscles of workers engaged in mild repetitive tasks is a common occupational health problem, much is unknown about the associated structural and biochemical changes. In this study, we compared the muscle energy metabolism of the extrinsic finger extensor musculature in instrumentalists suffering from work-related pain with that of healthy control instrumentalists using non-invasive phosphorus magnetic resonance spectroscopy ((31)P-MRS). We hypothesize that the affected muscles will show alterations related with an impaired energy metabolism.. We studied 19 volunteer instrumentalists (11 subjects with work-related pain affecting the extrinsic finger extensor musculature and 8 healthy controls). We used (31)P-MRS to find deviations from the expected metabolic response to exercise in phosphocreatine (PCr), inorganic phosphate (Pi), Pi/PCr ratio and intracellular pH kinetics. We observed a reduced finger extensor exercise tolerance in instrumentalists with myalgia, an intracellular pH compartmentation in the form of neutral and acid compartments, as detected by Pi peak splitting in (31)P-MRS spectra, predominantly in myalgic muscles, and a strong association of this pattern with the condition.. Work-related pain in the finger extrinsic extensor muscles is associated with intracellular pH compartmentation during exercise, non-invasively detectable by (31)P-MRS and consistent with the simultaneous energy production by oxidative metabolism and glycolysis. We speculate that a deficit in energy production by oxidative pathways may exist in the affected muscles. Two possible explanations for this would be the partial and/or local reduction of blood supply and the reduction of the muscle oxidative capacity itself.

Topics: Adolescent; Adult; Energy Metabolism; Exercise; Exercise Tolerance; Female; Fingers; Humans; Hydrogen-Ion Concentration; Intracellular Space; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Muscle, Skeletal; Music; Neuromuscular Diseases; Occupational Diseases; Pain; Phosphates; Phosphocreatine; Time Factors; Young Adult

Physiological alterations following unaccustomed eccentric exercise in an isokinetic dynamometer of the right m. quadriceps until exhaustion were studied, in order to create a model in which the physiological responses to physiotherapy could be measured. In experiment I (exp. I), seven selected parameters were measured bilaterally in 7 healthy subjects at day 0 as a control value. Then after a standardized bout of eccentric exercise the same parameters were measured daily for the following 7 d (test values). The measured parameters were: the ratio of phosphocreatine to inorganic phosphate (PCr/Pi), the ratio of inorganic phosphate to adenosintriphosphate (Pi/ATP), the ratio of phosphocreatine to adenosintriphosphate (PCr/ATP) (all three ratios measured with 31P-nuclear magnetic resonance spectroscopy), dynamic muscle strength, plasma creatine kinase (CK), degree of pain and "muscle" blood flow rate (133Xenon washout technique). This was repeated in experiment II (exp. II) 6-12 months later in order to study reproducibility. In experiment III (exp. III), the normal fluctuations over 8 d of the seven parameters were measured, without intervention with eccentric exercise in 6 other subjects. All subjects experienced pain, reaching a maximum 48 h after eccentric exercise in both exp. I and II. A systematic effect over time for CK (increasing 278% resp. 308%), muscle strength (decreasing more than 10%), PCr/Pi (decreasing 31% resp. 43%) and Pi/ATP (increasing 55% resp. 99%) was found in both exp. I and II (P < 0.05), but not in exp. III. No significant difference was observed between exp. I and II for CK, blood-flow rate, concentric muscle strength, PCr/Pi, Pi/ATP and PCr/ATP. It is concluded that pathophysiological alterations in m. quadriceps following eccentric exercise can be induced and can be reproduced after an interval of 6 months. Thus, this model can be used to study the effects of physiotherapy.

Topics: Adenosine Triphosphate; Adult; Creatine Kinase; Exercise; Female; Humans; Middle Aged; Muscle, Skeletal; Pain; Phosphates; Phosphocreatine; Time Factors

The aim of this study was to measure if passive stretching would influence delayed onset muscle soreness (DOMS), dynamic muscle strength, plasma creatine kinase concentration (CK) and the ratio of phosphocreatine to inorganic phosphate (PCr/P(i)) following eccentric exercise. Seven healthy untrained women, 28-46 years old, performed eccentric exercise with the right m. quadriceps in an isokinetic dynamometer (Biodex, angle velocity: 60 degrees.s-1) until exhaustion, in two different experiments, with an interval of 13-23 months. In both experiments the PCr/P(i) ratio, dynamic muscle strength, CK and muscle pain were measured before the eccentric exercise (day 0) and the following 7 d. In the second experiment daily passive stretching (3 times of 30 s duration, with a pause of 30 s in between) of m. quadriceps was included in the protocol. The stretching was performed before and immediately after the eccentric exercise at day 0, and before measurements of the dependent variables daily for the following 7 d. The eccentric exercise alone led to significant decreases in PCr/P(i) ratio (P < 0.001) and muscle strength (P < 0.001), and an increase in CK concentration (P < 0.01). All subjects reported pain in the right m. quadriceps with a peak 48 h after exercise. There was no difference in the reported variables between experiments one and two. It is concluded that passive stretching did not have any significant influence on increased plasma-CK, muscle pain, muscle strength and the PCr/P(i) ratio, indicating that passive stretching after eccentric exercise cannot prevent secondary pathological alterations.

Topics: Adult; Creatine Kinase; Exercise; Female; Humans; Middle Aged; Muscle, Skeletal; Pain; Phosphates; Phosphocreatine; Time Factors

We used ³¹P-magnetic resonance spectroscopy to test the hypothesis that exercise-induced muscle damage (EIMD) alters the muscle metabolic response to dynamic exercise, and that this contributes to the observed reduction in exercise tolerance following EIMD in humans. Ten healthy, physically active men performed incremental knee extensor exercise inside the bore of a whole body 1.5-T superconducting magnet before (pre) and 48 h after (post) performing 100 squats with a load corresponding to 70% of body mass. There were significant changes in all markers of muscle damage [perceived muscle soreness, creatine kinase activity (434% increase at 24 h), and isokinetic peak torque (16% decrease at 24 h)] following eccentric exercise. Muscle phosphocreatine concentration ([PCr]) and pH values during incremental exercise were not different pre- and post-EIMD (P > 0.05). However, resting inorganic phosphate concentration ([P(i)]; pre: 4.7 ± 0.8; post: 6.7 ± 1.7 mM; P < 0.01) and, consequently, [P(i)]/[PCr] values (pre: 0.12 ± 0.02; post: 0.18 ± 0.05; P < 0.01) were significantly elevated following EIMD. These mean differences were maintained during incremental exercise (P < 0.05). Time to exhaustion was significantly reduced following EIMD (519 ± 56 and 459 ± 63 s, pre- and post-EIMD, respectively, P < 0.001). End-exercise pH (pre: 6.75 ± 0.04; post: 6.83 ± 0.04; P < 0.05) and [PCr] (pre: 7.2 ± 1.7; post: 14.5 ± 2.1 mM; P < 0.01) were higher, but end-exercise [P(i)] was not significantly different (pre: 19.7 ± 1.9; post: 21.1 ± 2.6 mM, P > 0.05) following EIMD. The results indicate that alterations in phosphate metabolism, specifically the elevated [P(i)] at rest and throughout exercise, may contribute to the reduced exercise tolerance observed following EIMD.

Topics: Adolescent; Adult; Analysis of Variance; Biomarkers; Biomechanical Phenomena; Creatine Kinase, MM Form; Energy Metabolism; Exercise; Exercise Tolerance; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Muscle Contraction; Muscle Fatigue; Muscle, Skeletal; Muscular Diseases; Pain; Pain Measurement; Phosphates; Phosphocreatine; Phosphorus Isotopes; Time Factors; Torque; Young Adult

In this study, we examined muscle metabolic and acid-base status during incremental wrist extension exercise in the forearm of individuals with work-related myalgia (WRM). Eighteen women employed in full-time occupations involving repetitive forearm labor were recruited in this cross-sectional study. Nine of these women were diagnosed with WRM, while the other nine had no previous WRM history and were used as age-matched controls (Con). Phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) was used to noninvasively monitor the intracellular concentrations of phosphocreatine ([PCr]) and inorganic phosphate ([P(i)]) as well as intracellular pH (pH(i)) status during exercise in WRM and Con. We observed a 38% decreased work capacity in WRM compared with Con [0.18 W (SD 0.03) vs. 0.28 W (SD 0.10); P = 0.007]. Piecewise linear regression of the incremental exercise data revealed that the onset of a faster decrease in pH(i) (i.e., the pH threshold, pHT) and the onset of a faster increase in log([P(i)]/[PCr]) (i.e., the phosphorylation threshold, PT) occurred at a 14% relatively lower power output in WRM [pHT: 45.2% (SD 5.3) vs. 59.0% (SD 4.6), P < 0.001; PT: 44.8% (SD 4.3) vs. 57.8% (SD 3.1), P < 0.001; % of peak power output, Con vs. WRM, respectively]. Monoexponential modeling of the kinetics of [PCr] and pH(i) recovery following exercise demonstrated a slower (P = 0.005) time constant (tau) for [PCr] in WRM [113 s (SD 25)] vs. Con [77 s (SD 23)] and a slower (P = 0.007) tau for pH(i) in WRM [370 s (SD 178)] vs. Con [179 s (SD 52)]. In conclusion, our results suggest that WRM is associated with an increased reliance on nonoxidative metabolism. Possible mechanisms include a reduction in local muscle blood flow and perfusion, an increased ATP cost of force production, or both.

Topics: Acid-Base Equilibrium; Adult; Cross-Sectional Studies; Exercise; Exercise Tolerance; Female; Forearm; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Middle Aged; Muscle Fatigue; Muscle Strength; Muscle, Skeletal; Occupations; Pain; Phosphates; Phosphocreatine; Phosphorylation

To investigate the metabolic and functional status of muscles of fibromyalgia (FM) patients, using P-31 magnetic resonance spectroscopy (MRS).. Twelve patients with FM and 11 healthy subjects were studied. Clinical status was assessed by questionnaire. Biochemical status of muscle was evaluated with P-31 MRS by determining concentrations of inorganic phosphate (Pi), phosphocreatine (PCr), ATP, and phosphodiesters during rest and exercise. Functional status was evaluated from the PCr/Pi ratio, phosphorylation potential (PP), and total oxidative capacity (Vmax).. Patients with FM reported greater difficulty in performing activities of daily living as well as increased pain, fatigue, and weakness compared with controls. MRS measurements showed that patients had significantly lower than normal PCr and ATP levels (P < 0.004) and PCr/Pi ratios (P < 0.04) in the quadriceps muscles during rest. Values for PP and Vmax also were significantly reduced during rest and exercise.. P-31 MRS provides objective evidence for metabolic abnormalities consistent with weakness and fatigue in patients with FM. Noninvasive P-31 MRS may be useful in assessing clinical status and evaluating the effectiveness of treatment regimens in FM.

Topics: Adenosine Triphosphate; Adult; Fatigue; Female; Fibromyalgia; Health Status; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle Weakness; Muscle, Skeletal; Pain; Phosphates; Phosphocreatine; Phosphorus; Physical Exertion; Self-Assessment; Thigh

The purpose of this study was to evaluate changes in muscle soreness and serum enzyme activity following consecutive drop jumps. Seven male subjects (mean age 30.6 years) performed drop jumps from a 80-cm box height every 7 s until exhaustion (mean = 114 drop jumps). A questionnaire was used to assess muscle soreness (0 = no pain, 7 = unbearable painful) both pre- and post-exercise (0, 12, 24, 36 and 48 h, and 3, 4 and 5 days after the exercise). Blood samples were also taken from three subjects at each of these times. For the other four subjects, blood samples were taken pre-exercise and 0, 12 and 36 h and 5 days post-exercise only. Although there was large inter-subject variability in the development of muscle soreness, all the subjects reported muscle soreness in their lower extremity muscles, especially in the quadriceps femoris. Muscle soreness developed significantly (P less than 0.01) over time, its peak (mean +/- S.E. = 3.7 +/- 0.7) occurring 12-48 h post-exercise. Serum enzyme activity changed significantly over time (P less than 0.05), but the changes were small. Not one subject showed a large increase in creatine kinase, and the average increase was less than 1.3 times as much as the pre-exercise level throughout the period of study. These results suggest that the muscle damage that occurs after drop jumping is not associated with a large release of muscle enzymes into the blood, and muscle soreness is not necessarily related to enzyme elevation following drop jumps.

Topics: Adult; Aspartate Aminotransferases; Exercise; Humans; L-Lactate Dehydrogenase; Male; Muscles; Pain; Phosphocreatine; Sports