Joanne Phoenix

In vivo model of muscle pain: Quantification of intramuscular chemical, electrical, and pressure changes associated with saline-induced muscle pain in humans

Abstract Intramuscular injection of hypertonic saline is a good model to study human muscle pain (Kellgren 1938). The present study concerns the intramuscular (i.m.) pain mediators in saline‐induced muscle pain. In experiment 1, the diffusion of infused hypertonic and isotonic saline (0.5 ml) in m. tibialis anterior was illustrated by magnetic resonance imaging (MRI) in one subject. In experiment 2, six volunteers received four sequential infusions (0.5 ml given at 5 min intervals) of isotonic saline and thereafter four sequential infusions (0.5 ml given at 5 min intervals) of hypertonic saline into m. tibialis anterior. The isotonic and hypertonic saline infusions were computer‐controlled and separated by 20 min. The muscle pain intensity was assessed by continuous recordings on a visual analogue scale (VAS). One microdialysis probe was inserted 1 cm from the infusion needle in m. tibialis anterior and another probe in the other m. tibialis anterior. Concentrations of the i.m. sodium, potassium, magnesium, and prostaglandin E2 (PGE2) were assessed from the dialysates. Intramuscular electromyography (EMG) and pressure were assessed in the area of the infused saline. In experiment 1, the infusion of hypertonic and isotonic saline created a visible saline‐pool on the MRI scans. These saline‐pool volumes were stable and not correlated to the pain scores. In experiment 2, infusion of isotonic saline produced little pain compared to infusion of hypertonic saline. Maximal pain was reported after the first infusion of hypertonic saline and thereafter the pain gradually decreased with subsequent infusions of hypertonic saline. During infusion of hypertonic saline the i.m. sodium and potassium concentrations increased significantly, i.m. magnesium concentration tended to be increased, and the i.m. PGE2 concentration tended to be decreased although these changes were not significant. The i.m. EMG was smaller during and after infusions of hypertonic saline compared with isotonic saline. The i.m. pressure was not different during the infusions of hypertonic and isotonic saline but was increased between the infusions of hypertonic saline. This study has shown that i.m. infusion of hypertonic saline produced a saline‐pool, causing the i.m. pressure to increase. Possibly, pain activation and cessation are related to increased intramuscular sodium and potassium content respectively.

Objective quantification of muscle and fat in human dystrophic muscle by magnetic resonance image analysis

Information about changes in muscle composition has to date been primarily restricted to histological examination of biopsy samples or qualitative assessment of images obtained using a variety of techniques (e.g., ultrasound, CT, and MRI). We describe the development of a quantitative method for the analysis of muscle composition using MR T2 relaxation time mapping and image analysis. This approach provides an objective means of studying muscle and, when used in conjunction with force production measurements, may provide an accurate measure of response to muscle therapy.

Effect of vitamin B6 supplementation in McArdle's disease: a strategic case study

A patient-blind study into the effect of a 10-week cessation of long-term vitamin B6 supplementation on B6 status and performance in McArdles disease is reported. Muscle performance was assessed both subjectively and objectively by an ischaemic fatiguing protocol of the adductor pollicis muscle. Nine weeks after withdrawal of supplementation, vitamin B6 status had changed from adequacy to inadequacy and the force loss during the ischaemic fatiguing protocol had increased at all frequencies studied. The patient reported decreased exercise tolerance after 7 weeks and by the tenth week was experiencing an increase in muscle cramps. Vitamin B6 status and muscle performance may be linked in McArdles disease and there is potential for enhancement of performance by B6 supplementation.

Estimation of body composition in muscular dystrophy by MRI and stereology

We have applied the Cavalieri method of modern design stereology with magnetic resonance imaging for estimating the volume of whole‐body muscle and fat compartments in four patients with muscular dystrophy, a patient with myopathy, five controls, an anorexic subject, and a body builder. Detailed systematic series (ie, 50) of axial MR images (T1‐weighted, TR/TE 400/10 msec) were obtained throughout the whole body of each subject. The results showed that 15, 20, and 35 axial sections through the body are sufficient to secure coefficients of error (CEs) on the estimates of total muscle and fat volume of around 10%, 5%, and 3% respectively in muscular dystrophy patients and controls. The mean normalized volumes of muscle in four muscular dystrophy patients were decreased by 27% (t‐test: P < 0.05), and those of total fat were increased by 12% (t‐test: P > 0.05) relative to controls. The Cavalieri method provides a direct, efficient, and mathematically unbiased approach for studying human body compartments and may have application in assessing treatment efficacy in patients with muscular dystrophy. J. Magn. Reson. Imaging 2000;12:467–475.

The effect of vitamin E analogues and long hydrocarbon chain compounds on calcium-induced muscle damage. A novel role for α-tocopherol?

Abstract Previous studies have demonstrated that supplemental α-tocopherol inhibited calcium-induced cytosolic enzyme efflux from normal rat skeletal muscles incubated in vitro and suggested that the protective action was mediated by the phytyl chain of α-tocopherol [1]. In order to investigate this further a number of hydrocarbon chain analogues of tocopherol (7.8-dimethyl tocol, 5,7-dimethyl tocol, tocol, α-tocotrienol, α-tocopherol [10], vitamin K1, vitamin K1 [10], vitamin K1 diacetate, vitamin K2 [20], phytyl ubiquinone and retinol) were tested for any ability to inhibit calcium ionophore, A23187, induced creatine kinase (CK) enzyme efflux. Some compounds were found to be very effective inhibitors and comparison of their structures and ability and to inhibit TBARS production in muscle homogenates revealed that the effects did not appear related to antioxidant capacity or chromanol methyl groups, but rather the length and structure of the hydrocarbon chain was the important mediator of the effects seen.

Effects of calcium ionophore on vitamin E-deficient rat muscle

Damage to skeletal muscles may be mediated via free radicals or intracellular calcium overload. To look for inter-relationships between these pathways we have examined the effect of intracellular Ca overload on muscles from rats fed on either a vitamin E-deficient or vitamin E-sufficient diet and assessed the non-enzymic lipid peroxidation in these muscles by examining the production of thiobarbituric acid reactive substances by homogenates. Vitamin E-deficient muscles were more susceptible to Ca-induced intracellular enzyme efflux and this was acutely corrected by supplementation of the external medium with 230 mumol alpha-tocopherol/l. Vitamin E-deficient muscles showed increased levels of basal lipid peroxides and were more susceptible to iron-catalysed lipid peroxidation. Addition of the Ca ionophore A23187 increased lipid peroxidation in vitamin E-deficient muscle homogenates, but had the opposite effect in vitamin E-sufficient muscles. These results demonstrate that vitamin E-deficient muscle has an increased susceptibility to intracellular Ca overload, but that this effect cannot be explained by a direct stimulatory effect of the ionophore on non-enzymic lipid peroxidation.

The effect of motor learning in facioscapulohumeral muscular dystrophy patients.

Abstract Two models of motor learning (ML) practice (complex and simple) were used to investigate upper limb function in individuals with facioscapulohumeral dystrophy (FSHD). The effect of ML practice was studied by examining changes in the ability to undertake a simulated drinking task. In the complex model, seven FSHD patients and seven age- and gender-matched healthy volunteers were studied. Performance was assessed by measurement of the electromyographic (EMG) activity of the biceps brachii and brachioradialis, elbow joint flexion, shoulder joint flexion and abduction, maximum acceleration at the onset of movement, movement time and reaction time, both before and after a 30-min complex ML task. In the simple model, a second group of six FSHD patients and six age- and gender-matched healthy subjects were studied. The same parameters were measured as for the complex ML task, except that the EMG activity of the triceps and deltoid muscles (anterior part) were measured instead of that of the brachioradialis. In both studies, the FSHD patients showed significantly larger values for all parameters except the flexion of shoulder joint and reaction time, compared with controls before the ML task. In the FSHD group, while the complex ML resulted in decreases in the brachioradialis EMG activity (P < 0.005) and reaction time (P < 0.0001), the simple ML model resulted in significant changes towards the normal value in all parameters measured except shoulder flexion. The change in the measured variables towards normal values indicates that ML may help to improve performance in FSHD.

Interrelationships between metabolism of glycogen phosphorylase and pyridoxal phosphate - implications in McArdle's Disease

This chapter discusses the interrelationships between metabolism of glycogen phosphorylase and pyridoxal phosphate-implications in Mcardles disease. Glycogen phosphorylase is the key regulator of glycogenolysis, catalyzing the phosphorolysis of glycogen to produce glucose-1-phosphate. The rate of degradation of phosphorylase measured by cofactor labeling is same as that measured by continuous infusion of radiolabeled amino acids. The principle of using radiolabeled vitamin B6 as a label for phosphorylase degradation is straightforward and takes the form of a classical pulse chase protocol. The chapter studies muscle-wasting processes in a mouse, and the role of degradation in muscle growth on the chicken. In McArdles disease, the whole body phosphorylase-derived pool acts as a “buffer” to compensate for day-to-day variation in vitamin B6 intake. Analysis of the kinetics in McArdles patients defines the role of muscle phosphorylase in the compartmentalization of vitamin B6.

The Effect of Motor Learning on Upper Limb Performance in Fascioscapulohumeral Muscular Dystrophy Patients

Muscular dystrophy (MD) patients suffer from progressive weakness resulting in disability. The effect of exercise to overcome weakness in MD patients is doubtful and there is some evidence that showed overloading on dystrophic muscle may increase the progress of disease (Johnson and Braddom, 1971). Motor learning (ML) therapy could be another possibility to improve muscle performance, as it may programme the central nervous system to drive weak muscles more effectively. Although ML may be used to improve performance in patients with central nervous system dysfunction (Carr and Shepherd, 1987) there has been no investigation of the benefits of such therapy in MD. We therefore investigated the effect of a ML protocol on upper limb function in fascioscapulohumeral MD (FSHD) patients.