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A randomized clinical trial comparing chiropractic adjustments to muscle relaxants for subacute low back pain.

BACKGROUND: The adult lifetime incidence for low back pain is 75% to 85% in the United States. Investigating appropriate care has proven difficult, since, in general, acute pain subsides spontaneously and chronic pain is resistant to intervention. Subacute back pain has been rarely studied. OBJECTIVE: To compare the relative efficacy of chiropractic adjustments with muscle relaxants and placebo/sham for subacute low back pain. DESIGN: A randomized, double-blind clinical trial. METHODS: Subjects (N = 192) experiencing low back pain of 2 to 6 weeks' duration were randomly allocated to 3 groups with interventions applied over 2 weeks. Interventions were either chiropractic adjustments with placebo medicine, muscle relaxants with sham adjustments, or placebo medicine with sham adjustments. Visual Analog Scale for Pain, Oswestry Disability Questionnaire, and Modified Zung Depression Scale were assessed at baseline, 2 weeks, and 4 weeks. Schober's flexibility test, acetaminophen usage, and Global Impression of Severity Scale (GIS), a physician's clinical impression used as a secondary outcome, were assessed at baseline and 2 weeks. RESULTS: Baseline values, except GIS, were similar for all groups. When all subjects completing the protocol were combined (N = 146), the data revealed pain, disability, depression, and GIS decreased significantly (P <.0001); lumbar flexibility did not change. Statistical differences across groups were seen for pain, a primary outcome, (chiropractic group improved more than control group) and GIS (chiropractic group improved more than other groups). No significant differences were seen for disability, depression, flexibility, or acetaminophen usage across groups. CONCLUSION: Chiropractic was more beneficial than placebo in reducing pain and more beneficial than either placebo or muscle relaxants in reducing GIS.

Acetaminophen↗

Commonly used muscle relaxant therapies for acute low back pain: a review of carisoprodol, cyclobenzaprine hydrochloride, and metaxalone.

BACKGROUND: Low back pain is a leading reason for primary care visits. Many treatment options are available, but some lack scientific support. OBJECTIVE: The aim of this review was to discuss the etiology of low back pain and the relative risks and benefits of muscle relaxants commonly prescribed for the management of back pain. METHODS: We searched Intercontinental Marketing Services data for January 2003 through January 2004 to determine the most commonly prescribed agents for the management of musculoskeletal pain. Carisoprodol, cyclobenzaprine hydrochloride, and metaxalone represented >45% of all such prescriptions. Cochrane Library, MEDLINE, and EMBASE databases were searched (time frame: 1960 through January 2004; search terms: back pain, carisoprodol, cyclobenzaprine, metaxalone, muscle relaxants, and pharmacotherapy) and reference lists of identified articles were hand-searched. RESULTS: Three trials of carisoprodol (N = 197) were located in the Cochrane Library database. Two double-blind, randomized, placebo-controlled trials evaluating the safety and efficacy of cyclobenzaprine hydrochloride (N = 1405) were identified in the literature. Three double-blind, placebo-controlled trials were identified for metaxalone (N = 428) in 2 reports. The types of adverse events seen with these agents involved the central nervous system, including drowsiness/sedation, fatigue, and dizziness. However, the efficacy of cyclobenzaprine hydrochloride was shown to be independent of its sedative effects, which were dose related. The potential for abuse with carisoprodol is of growing concern. CONCLUSIONS: Analgesic pain management for low back pain due to muscle spasm may be combined with a muscle relaxant. Cyclobenzaprine hydrochloride has the most recent and largest clinical trials demonstrating its benefit, but carisoprodol and metaxalone also appear to be effective. However, carisoprodol's usefulness is mitigated by its potential for abuse.

Amitriptyline↗

Developmental toxicity of nondepolarizing muscle relaxants in cultured rat embryos.

Evidence of developmental toxicity of clinically used nondepolarizing muscle relaxants was sought in rat embryos grown in culture. Embryos were explanted at 8 AM on day 9 of gestation (presomite stage, plug day = day 0), and were cultured in rotating bottles with medium containing various concentrations of d-tubocurarine, pancuronium, atracurium, and vecuronium. At 10 AM on day 11 of gestation (forelimb bud stage), culture was terminated and embryos were examined for general morphology. Treatment with tested agents resulted in dose-dependent developmental toxicity; namely, growth retardation seen as decreased crown-rump length, decreased number of somite pairs, and morphologic abnormalities. However, the concentrations that caused toxicity were at least 30-fold greater than serum concentrations clinically achieved in the mother. We conclude that these muscle relaxants have a low potential for causing developmental toxicity during organogenesis.

Animals↗

Gravity cavernosometry and assessment of complete smooth muscle relaxation: helpful in the differential diagnosis of cavernous leakage?

OBJECTIVE: To establish whether the relationship between cavernosal pressures and gravitational pressures of infused liquid during gravity cavernosometry is linear when complete smooth muscle relaxation is achieved and whether the determination of this relationship could be helpful in the differential diagnosis between organic and functional cavernous leakage. METHODS: Gravity cavernosometry was performed in 50 impotent patients. The cavernosal pressure was measured at at least four different gravitational pressures of the infused liquid. RESULTS: A linear relationship was obtained in all patients with normal maximal cavernosal pressure at gravity cavernosometry. A flat or nonlinear relationship was found in those with abnormal maximal pressure, whatever the cause of cavernous leakage. CONCLUSIONS: A linear relationship between cavernosal and gravitational pressures characterizes complete smooth muscle relaxation during gravity cavernosometry. However, the usefulness of the determination of this relationship is not yet established.

Adult↗

Use of the muscle relaxant atracurium in anephric patients: preliminary communication.

Atracurium is a new, non-depolarizing muscle relaxant which rapidly breaks down in vivo and appears to require neither renal nor hepatic function for its elimination. As the commonly used non-depolarizing muscle relaxants carry the risk of prolonged effect when used in anephric patients, atracurium appears to have special promise in this situation. A preliminary account of the successful use of the relaxant in 20 anephric patients is recorded and evidence presented that atracurium is, indeed, a suitable agent for use in patients with renal failure.

Adjuvants, Anesthesia↗

Cardiac troponin I phosphorylation increases the rate of cardiac muscle relaxation.

Cardiac troponin (Tn) I (CTnI), compared with skeletal TnI, contains extra amino acids (32 to 33) at its amino terminus, including two adjacent serine residues. These two serine residues are believed to be phosphorylated by protein kinase A (PKA) upon stimulation of the heart by beta-agonists. In this study, we found that phosphorylation of a cardiac skinned muscle preparation by PKA, mainly at CTnI, results in a decrease in the Ca2+ sensitivity of muscle contraction. The pCa50 decreased by approximately 0.27 +/- 0.06 pCa units upon phosphorylation. To study cardiac muscle relaxation, we used diazo-2, a photolabile Ca2+ chelator with a low Ca2+ affinity in its intact form that is converted to a high-affinity form after photolysis. We found that the rate of cardiac muscle relaxation increased from a time of half-relaxation (t1/2) = 110 +/- 10 milliseconds to t1/2 = 70 +/- 8 milliseconds after CTnI phosphorylation. This result demonstrates that CTnI phosphorylation can be linked with the increased rate of muscle relaxation in a relatively intact muscle preparation. Since CTnI phosphorylation has been shown previously to affect the Ca2+ affinity and Ca2+ off-rate of CTnC in vitro, it is likely that the faster relaxation seen here reflects faster dissociation of Ca2+ from cardiac TnC (CTnC). Model calculations show that increased dissociation of Ca2+ from CTnC, coupled with the faster uptake of Ca2+ by the sarcoplasmic reticulum stimulated by PKA phosphorylation of phospholamban, can account for the faster relaxation seen in the inotropic response of the heart to catecholamines.

Adenosine Triphosphatases↗

Facilitation of isoproterenol induced airway smooth muscle relaxation by nifedipine.

The facilitating effect of nifedipine on isoproterenol induced airway smooth muscle relaxation was studied in guinea pig tracheas. For isometric force measurement, 4 mm tracheal cylinders were suspended in incubation chambers in oxygenated physiologic medium. After 90 minutes of equilibration under 2 grams resting tension, at a temperature of 37 degrees C and pH of 7.4, concentration response curves for isoproterenol were performed with and without the addition of a 1 X 10(-5)M nifedipine dose. The experiments were then repeated using tissues precontracted with histamine. Our data show that in the nifedipine pretreated tissues, the EC50 of isoproterenol is shifted to the left (p less than 0.05) probably due to further reduction in cytosolic calcium by nifedipine. Our findings suggest that nifedipine might have a role in the treatment of asthma and obstructive airway disease.

Animals↗

The nature of the muscle-relaxing factor. II. Some physicochemical properties.

High speed centrifugal fractionation of homogenates of rabbit skeletal muscle has led to the discovery of a soluble muscle-relaxing factor in the homogenate. Assay of the relaxing activity with deoxycholate-treated myofibrils and reconstituted actomyosin systems has established that the activity is not produced by the presence of contaminants. Relaxing activity could be removed or destroyed by charcoal, dialysis, prolonged heating, and treatment with the chelating resin, chelex-100, making it improbable that the effect is due simply to calcium deficiency. Many of the characteristics of this muscle-relaxing factor suggest that it is very similar to or the same as the factor formed by the incubation of muscle granule fractions and ATP. Evidence is presented that some soluble protein component is involved in the stabilization of the factor. The relaxing activity could be separated from the high molecular weight material in the supernatant by the technique of gel filtration. On the basis of the gel used, the molecular weight of the active agent should be less than 4000.

Actomyosin↗

Fasciculation frequency changes at different length of relaxed muscle.

We have studied, in chronically denervated muscles, fasciculation potentials (FPs) which were clearly identified when the muscles were either relaxed or passively stretched. The frequency of 10 FPs was determined in both positions in seven patients. In stretched muscles, two FPs were no longer recorded, and the mean FP frequency decreased significantly (P < .01). There was also a decrease of the FP amplitude. As FPs are frequently associated with ordinary muscle cramps, stretching of the muscle may lessen the frequency of FPs by the same mechanism which stops cramps.

Adult↗

Synthesis and skeletal muscle relaxant activity of quaternary ammonium salts of dantrolene and clodanolene.

A series of quaternary ammonium salts of dantrolene and clodanolene was prepared and evaluated for skeletal muscle relaxant activity. The quaternary ammonium salts exhibit greater aqueous solubility and, therefore, facilitate intravenous administration. One member of this series, although less effective orally, exhibited greater aqueous solubility than the sodium salt. When administered intravenously, it was a more potent antagonist of skeletal muscle contraction and yielded comparable therapeutic and muscle relaxant efficacy indexes.

Animals↗

Muscle relaxant properties of the identified metabolites of dantrolene.

Identified metabolites of dantrolene, a skeletal muscle relaxant, were studied for inhibition of skeletal muscle contractions. Inhibition of muscle contractions were studied in vivo in the rat gastrocnemius muscle preparation, and in vitro using isolated rat diaphragm strips. Dantrolene (D) and 5-hydroxydantrolene (5-HD) inhibited muscle contraction responses in a dose dependent manner, both in vivo and in vitro. 5-HD was less potent than D.

Animals↗

Effects of smooth muscle relaxant (aspaminol) on Ca-uptake by mitochondrial and microsomal fractions from rat uterus.

A smooth muscle relaxant, Aspaminol (1,1-diphenyl-3-piperidinobutanol hydrochloride) relaxed a KCl-depolarized rat uterus and shifted a dose response curve of CaCl2 towards higher doses. Asparminol, a teritary amine, may penetrate into the KCl-depolarized muscle cells. In order to study mechanisms for relaxation of the KCl-depolarized rat uterus by Aspaminol, effects of Aspaminol on Ca-uptake by mitochondrial and microsomal fractions from the rat uterus were studied. Aspaminol inhibited Ca-uptake by both fractions. Inhibition of Ca-uptake by the mitochondrial fraction seems to increase intracellular Ca2+. Therefore, inhibition of Ca-uptake by the mitochondrial fraction is considered to be not associated with relaxation of uterus induced by Aspaminol. Since the microsomal fraction is known to form microsacs, the microsomal fraction was used as smooth muscle models. Inhibitory effect of Aspaminol on Ca-uptake by the microsomal fraction suggest a decrease in the intracellular concentration of Ca2+ of the uterine smooth muscle relaxed under the influence of Aspaminol.

Animals↗

Mechanisms of depressant action of muscle relaxants on spinal reflexes: participation of membrane stabilizing action.

The participation of local anesthetic action in spinal reflex inhibition produced by mephenesin-type muscle relaxants was examined by comparing the local anesthetic effects (in vitro), the depressant effects on muscle afferent discharges (in situ) and the depressant effects on spinal reflexes (in situ) of the drugs in rats. At doses producing depression of spinal reflexes, mephenesin, tolperisone (mephenesin-type) and lidocaine (local anesthetic) reduced the frequency of afferent discharges from the muscle. The order of reducing afferent discharges by these drugs corresponded to that of their conduction blocking activities in the isolated sciatic nerve of rats. These results suggest the participation of a membrane stabilizing action in spinal reflex inhibition produced by mephenesin-type muscle relaxants. Baclofen (non-mephenesin-type) did not show any local anesthetic action.

Action Potentials↗

[The effect of EMG level by EMG biofeedback with progressive muscle relaxation training on tension headache].

The purpose of this study is to assess if EMG biofeedback training with progressive muscle relaxation training is effective in reducing the EMG level in patients with tension headaches. This study which lasted from 23 October to 30 December 1989, was conducted on 10 females who were diagnosed as patients with tension headaches and selected from among volunteers at C. University in Seoul. The process of the study was as follows: First, before the treatment, the baseline was measured for two weeks and the level of EMG was measured five times in five minutes. And then EMG biofeedback training was used for six weeks, 12 sessions in all, and progressive muscle relaxation was done at home by audio tape over eight weeks. Each session was composed of a 5-minute baseline, two 5-minute EMG biofeedback training periods and a 5-minute self-control stage. Each stage was followed by a five minute rest period. So each session took a total of 40 minutes. The EMG level was measured by EMG biofeedback (Autogenic-Cyborg: M 130 EMG module). The results were as follows: 1. The average age of the subjects was 44.1 years and the average history of headache was 10.6 years (range: 6 months-20 years). 2. The level of EMG was lowest between the third and the fourth week of the training except in Cases I and IV. 3. The patients began to show a nonconciliatory attitude at the first session of the fifth week of the training.

Biofeedback, Psychology↗

Skeletal muscle relaxant action of an aqueous extract of Portulaca oleracea in the rat.

The aqueous extract of Portulaca oleracea produced skeletal muscle relaxation in rats following i.p. or oral administration, as assessed by the prolongation of pull-up time. The i.p. route of administration was more effective. When compared with chlordiazepoxide (20 mg/kg, i.p.), diazepam (40 mg/kg, i.p.) and dantrolene sodium (30 mg/kg, oral), the extract (200-1000 mg/kg, i.p.) proved a more effective skeletal muscle relaxant. With 1000 mg/kg i.p., 80% lethality was seen. The LD50 in an acute toxicity test in mice was 1040 mg/kg i.p.

Animals↗

New roles for cysteine and transsulfuration enzymes: production of H2S, a neuromodulator and smooth muscle relaxant.

The enzymes of the transsulfuration pathway also have the capacity to catalyze the desulfhydration of cysteine. Recent studies demonstrate a role of the transsulfuration enzymes, cystathionine gamma-lyase and cystathionine beta-synthase, in catalyzing the desulfhydration of cysteine in brain and smooth muscle. The H2S produced from cysteine functions as a neuromodulator and smooth muscle relaxant. In glutamatergic neurons, the production of H2S by cystathionine beta-synthase enhances N-methyl-D-aspartate (NMDA) receptor-mediated currents. In smooth muscle cells, H2S produced by cystathionine gamma-lyase enhances the outward flux of potassium by opening potassium channels, leading to hyperpolarization of membrane potential and smooth muscle relaxation.

Animals↗

Mechanism of smooth muscle relaxation by rociverine.

Experiments were carried out in vitro on a new antispasmodic drug, 2-(diethylamino)-1-methylethyl-cis-1-hydroxy[bicyclohexyl] -2-carboxylate (rociverine), to elucidate further the mechanism of its smooth-muscle relaxation. On the furtrethonium contractions of rat jejunum rociverine exerts both a competitive antagonism, about 3000 times less than that of atropine, and a noncompetitive antagonism equal to that of papaverine. Both on rat vas deferens and on rabbit aorta rociverine at low doses slightly potentiates the response to norepinephrine (unrelated to any inhibition of uptakes), whereas at higher doses it depresses the maximum effect, 10 times more on the vas deferens than on the aorta. Against calcium in the same preparations rociverine behaves as a competitive antagonist with 10 times less potency than verapamil on the vas deferens and 300 times less on the aorta. In negative inotropic and chronotropic action on guinea-pig atria rociverine is 300 and 100 times, respectively, less potent than verapamil and in negative inotropic action on KCl-depolarized guinea-pig ventricular strips, whose contractility is restored by histamine, it is 70 times less potent than verapamil. In sum, the smooth-muscle relaxant action of rociverine depends on a modest antimuscarinic action and a direct myolytic action, the latter probably being due to an inhibitory action on the transmembrane fluxes of Ca2+. The potency ratio relative to verapamil indicates that the anti-Ca2+ action of rociverine is greater on the visceral smooth muscle than on cardiac and vascular muscle.

Animals↗