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PubMed2003

Muscle relaxants for nonspecific low back pain: a systematic review within the framework of the cochrane collaboration.

STUDY DESIGN: A systematic review of randomized and/or double-blinded controlled trials. SUMMARY OF BACKGROUND DATA: The use of muscle relaxants in the management of nonspecific low back pain is controversial. It is not clear if they are effective, and concerns have been raised about the potential adverse effects involved. OBJECTIVES: The aim of this review was to determine if muscle relaxants are effective in the treatment of nonspecific low back pain. METHODS: A computer-assisted search of the Cochrane Library (Issue 2, 2002), MEDLINE (1966 up to October 2001), and EMBASE (1988 up to October 2001) was carried out. These databases were searched using the algorithm recommended by the Cochrane Back Review Group. References cited in the identified articles and other relevant literature were screened. Randomized and/or double-blinded controlled trials, involving patients diagnosed with nonspecific low back pain, treated with muscle relaxants as monotherapy or in combination with other therapeutic methods, were included for review. Two reviewers independently carried out the methodologic quality assessment and data extraction of the trials. The analysis comprised not only a quantitative analysis (statistical pooling) but also a qualitative analysis ("best evidence synthesis"). This involved the appraisal of the strength of evidence for various conclusions using a rating system based on the quality and outcomes of the studies included. Evidence was classified as "strong," "moderate," "limited," "conflicting," or "no" evidence. RESULTS: Thirty trials met the inclusion criteria. Twenty-three trials (77%) were of high quality; 24 trials (80%) were on acute low back pain. Four trials studied benzodiazepines, 11 nonbenzodiazepines, and 2 antispasticity muscle relaxants in comparison with placebo. Results showed that there is strong evidence that any of these muscle relaxants are more effective than placebo for patients with acute low back pain on short-term pain relief. The pooled relative risk for nonbenzodiazepines versus placebo after 2 to 4 days was 0.80 (95% confidence interval: 0.71 to 0.89) for pain relief and 0.49 (95% confidence interval: 0.25 to 0.95) for global efficacy. Adverse events, however, with a relative risk of 1.50 (95% confidence interval: 1.14 to 1.98) were significantly more prevalent in patients receiving muscle relaxants and especially the central nervous system adverse effects (relative risk 2.04; 95% confidence interval: 1.23 to 3.37). The various muscle relaxants were found to be similar in performance. CONCLUSIONS: Muscle relaxants are effective in the management of nonspecific low back pain, but the adverse effects require that they be used with caution. Trials are needed that evaluate if muscle relaxants are more effective than analgesics or nonsteroidal anti-inflammatory drugs.

Controlled Clinical Trials as Topic↗
PubMedDate not supplied

A clinical and pharmacologic review of skeletal muscle relaxants for musculoskeletal conditions.

Muscle strains and other musculoskeletal disorders (MSDs) are a leading cause of work absenteeism. Muscle pain, spasm, swelling, and inflammation are symptomatic of strains. The precise relationship between musculoskeletal pain and spasm is not well understood. The dictum that pain induces spasm, which causes more pain, is not substantiated by critical analysis. The painful muscle may not show EMG activity, and when there is, the timing and intensity often do not correlate with the pain. Clinical and physiologic studies show that pain tends to inhibit rather than facilitate reflex contractile activity. The decision to treat and choice of therapy are largely dictated by the duration, severity of symptoms, and degree of dysfunction. Trigger point injections are sometimes used with excellent results in the treatment of muscle spasm in myofacial pain and low-back pain. NSAIDs are used with much greater frequency than oral skeletal muscle relaxants (SMRs) or opioids in the treatment of acute MSDs. Unfortunately, remarkably little sound science guides the choice of drug for the treatment of acute, uncomplicated MSDs, and the evaluation of efficacy of one agent over another is complicated by numerous factors. Only a limited number of high-quality, randomized, controlled trials (RCTs) provide evidence of the effectiveness of NSAIDs or SMRs in the treatment of acute, uncomplicated MSDs. The quality of design, execution, and reporting of trials for the treatment of MSDs needs to be improved. The combination of an SMR and an NSAID or COX-2 inhibitor or the combination of SMR and tramadol/acetaminophen is superior to single agents alone.

Acute Disease↗
PubMed1996

The medullary reticular formation is a site of muscle relaxant action of diazepam on deep back and neck muscles in the female rat.

We tested the hypothesis that the effect of systemic injections of diazepam (DZ, 125 mg/kg) to reduce the quality of the reproductive behavior, lordosis, and to reduce the EMG of lumbar back muscles involved in lordosis (Schwartz-Giblin et al., 1984) is exerted through a reticulospinal pathway with cells of origin in the nucleus gigantocellularis that excites lumbar motoneurons indirectly (Robbins et al., 1990, Robbins et al., 1992). In contrast, DZ facilitates lordosis behavior when infused into the midbrain central gray (McCarthy et al., 1995). Direct deposits of crystalline mixtures of DZ (20-80 ng) in dextrose were delivered to the medullary reticular formation (MRF) by diffusion from a cannula inserted through a guide to which a bipolar stimulating electrode was attached. The multiunit EMG response evoked by 20 (300 ms long) stimulus trains was recorded in back and neck muscles, lateral longissimus and splenius before and 5, 15, 30 and 60 min after local DZ deposits. There was a significant reduction in EMG response over this time period when stimulus intensities were within the range of 1.2-1.5 times threshold (Friedman two-way non-parametric test, P < 0.002). Large amplitude motor units that provide large tensions were the most sensitive to DZ-induced inhibition. Control deposits of dextrose had no significant effect. Systemic injections of progesterone (1 mg, i.p.) 60 min after DZ deposits, but not after dextrose deposits, further reduced the MRF-evoked EMG responses over the course of 1 h. As predicted, DZ infusions into the midbrain central gray did not reduce the reticulospinal-evoked axial muscle response, consistent with the facilitatory effect of midbrain central gray infusions of DZ on the lordosis quotient. The results suggest that benzodiazepine agonists (if endogenous) acting at sites in the MRF would be effective muscle relaxants during pregnancy, prior to the fall in progesterone that precedes labor.

Animals↗
PubMed1999

Prevalence of muscle relaxant sensitivity in a general population: implications for a preoperative screening.

BACKGROUND: Muscle relaxants (MR) are responsible for 59% of peroperative anaphylactic reactions. A major issue would be to determine whether a systematic preoperative screening in the general population should be recommended. OBJECTIVE: The purpose of the study was to evaluate the prevalence of muscle relaxant sensitivity in a sample of the general population and to assess the role of possible risk factors. METHODS: Two hundred and fifty-eight subjects, aged 20-40 years, visiting a health care centre for a check-up were evaluated. Protocol included a questionnaire (occupation, symptoms of atopy, previous surgery, history of drug allergy), skin-prick tests to four commercial muscle relaxants and measurement of specific IgE against quaternary ammonium ions. Atopy was evaluated by skin-prick tests to common inhalant allergens and by a Phadiatop test. RESULTS: Of the study group, 9.3% had either a positive skin test to one or more muscle relaxant or a presence of specific IgE to quaternary ammonium ions. No risk factor was identified in the studied group. CONCLUSION: Since the rate of MR sensitivity is much higher than the anticipated rate of peroperative reactions due to allergy, a systematic preoperative screening for MR allergy should not be recommended for adults in a general population.

Adult↗
PubMed2006

Modeling of twitch fade based on slow interaction of nondepolarizing muscle relaxants with the presynaptic receptors.

Nondepolarizing muscle relaxants (MRs) diminish the indirectly evoked single twitch due to their binding to the postsynaptic receptors. Additionally, the MRs produce progressive diminution of successive twitches upon repetitive stimulation (fade). Our study addresses the generation of fade as observed under clinical situation. The study was conducted in two phases. In the clinical part, we have evaluated the time course of twitch depression and fade following the administration of several doses of three MRs (rocuronium, pancuronium, and cisatracurium). In the second part, we have modified our model of neuromuscular transmission to simulate the time course of twitch depression and fade. The MR was assumed to bind to a single site on the presynaptic receptor to produce fade. The rates of interaction with the presynaptic receptors were characterized in terms of the arbitrarily assigned equilibrium dissociation constant and the half-life for dissociation of the presynaptic complex. A method was developed to relate the release of acetylcholine to the occupancy of the presynaptic receptors. The strength of the first and the fourth twitch was calculated from the peak concentration of the activated postsynaptic receptors, i.e., of those receptors with both sites occupied by acetylcholine. Our results indicate that, while the affinity of the MR for the presynaptic receptor plays little role in the time course of fade, the rate of dissociation of the complex between the presynaptic receptors and the muscle relaxant may be critical in determining the time course of fade. Tentative estimates of this parameter are offered.

Acetylcholine↗
PubMed2004

Prescription of nonsteroidal anti-inflammatory drugs and muscle relaxants for back pain in the United States.

STUDY DESIGN: Secondary analysis of the 2000 Medical Expenditure Panel Survey (MEPS). OBJECTIVE.: To examine national prescription patterns of nonsteroidal anti-inflammatory drugs (NSAIDs) and muscle relaxants among individuals with back pain in the United States. SUMMARY OF BACKGROUND DATA: There is a lack of information on national prescription patterns of NSAIDs and muscle relaxants among individuals with back pain in the United States. METHODS: Traditional NSAIDs, cyclooxygenase-2-specific (COX-2) inhibitors, and muscle relaxants were investigated. Individuals with back pain were stratified by socio-demographic characteristics and geographic regions. For each medication category, overall prescribing frequency was compared across different strata and individual drug prescription was analyzed. RESULTS: Traditional NSAIDs, COX-2 inhibitors, and muscle relaxants, respectively, accounted for 16.3%, 10%, and 18.5% of total prescriptions for back pain in 2000. Among individual drugs, ibuprofen and naproxen accounted for most of the prescriptions for traditional NSAIDs (60%), whereas two thirds of the prescriptions for muscle relaxants were attributable to cyclobenzaprine, carisoprodol, and methocarbamol. Prescription of COX-2 inhibitors or muscle relaxants demonstrated wide variations across different regions. Several individual characteristics including age, race, and educational level were associated with the prescription of some of the medications. CONCLUSIONS: Neither traditional NSAIDs, nor COX-2 inhibitors, nor muscle relaxants dominated prescriptions for back pain. However, a small number of individual drugs were attributable to most of the prescriptions for traditional NSAIDs or muscle relaxants. The prescription of some of the medications demonstrated wide variations across different regions or different racial and educational groups. More studies are needed to understand the source of the variations and what constitutes optimal prescribing.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1984

Treatment of mild hypertension with progressive muscle relaxation. Predictive value of indexes of sympathetic tone.

Effects of progressive muscle relaxation (PMR) and of attention control were investigated in a prospective randomized trial of borderline or mild hypertensive patients. Both groups received placebo and had the same number of clinic return visits. After 22 weeks the average mean home BP in PMR decreased 3 mm Hg, whereas in controls BP increased 2 mm Hg. Progressive muscle relaxation had no significant effect on the clinic BP. The response to PMR was not uniform. Responders were characterized by faster heart rates and higher plasma norepinephrine levels. The responders also showed a decrease of anxiety scores during the trial. Progressive muscle relaxation is a time-consuming procedure. Blood pressure responses do not substantially exceed the placebo effects in unselected patients. However, relaxation may be suitable for young, anxious patients with mild hypertension who have a high resting sympathetic tone.

Adolescent↗
PubMed1981

The site of action of muscle relaxant purine nucleosides.

The effects of a series of purine nucleosides, including the novel marine natural product 1-methylisoguanosine, have been examined on muscle relaxation in conscious animals and on spinal reflexes and neuromuscular transmission in mice anaesthetized with sodium pentobarbitone. 1-Methylisoguanosine (5--15 mumol kg--1) and 2-chloroadenosine (1--5 mumol kg--1), both of which cause muscle relaxation in conscious animals, depressed both mono- and polysynaptic spinal reflexes but did not affect neuromuscular transmission. At much higher doses (300 mumol kg--1) both compounds did depress neuromuscular transmission. Adenosine and 1-methyladenosine did not produce muscle relaxation in conscious animals and only slightly depressed polysynaptic reflexes at the highest doses tested (300 mumol kg--1). Theophylline 50 mumol kg--1 enhanced polysynaptic reflexes and antagonized the depression of these reflexes by 1-methylisoguanosine. Neither adenosine nor 1-methylisoguanosine affected the development of tension by isolated diaphragm muscles in vitro. It is concluded that the muscle relaxant purine nucleosides 2-chloroadenosine and 1-methylisoguanosine produce their effects primarily by depressing activity in the central nervous system. Transmission at the neuromuscular junction is not affected at doses in the range of those producing muscle relaxation.

Animals↗
PubMed1986

Muscle relaxant action of phenobarbitone in genetically spastic rats: an electromyographic study.

The muscle relaxant effect of phenobarbitone was studied in genetically spastic rats which exhibit spontaneous tonic activity in the electromyogram (EMG) of the gastrocnemius muscle. Phenobarbitone, 10-30 mg/kg i.p., reduced the tonic activity in the EMG of the gastrocnemius muscle of such rats in a dose- and time-dependent manner. The GABA antagonists bicuculline, 2 mg/kg i.p., and picrotoxin, 2 and 3 mg/kg i.p., reduced the muscle relaxant effect of phenobarbitone, 20 and 30 mg/kg. The benzodiazepine receptor antagonists, Ro 15-1788, 5 mg/kg, and CGS 8216, 5 mg/kg (doses which do not affect tonic activity in the EMG), failed to alter the depressant effect of phenobarbitone 30 mg/kg, in the EMG. Beta-Carboline-3-carboxylic acid methylester (beta-CCM), 2 mg/kg i.p., while not affecting the tonic activity in the EMG, reversed the depressant effect of phenobarbitone, 30 mg/kg. Both Ro 15-1788, 5 mg/kg, and CGS 8216, 5 mg/kg, prevented the reversal of the depressant action of phenobarbitone, 30 mg/kg, produced by beta-CCM, 2 mg/kg. The results indicate that the muscle relaxant action of phenobarbitone in genetically spastic rats is mediated via GABA-related mechanisms and add further support to the hypothesis that both Ro 15-1788 and CGS 8216 are specific antagonists at benzodiazepine receptors, devoid of intrinsic activity at moderate doses. The results also suggest that reversal of the muscle relaxant action of phenobarbitone by beta-CCM is mediated via a GABA/benzodiazepine receptor/chloride ionophore complex.

Animals↗
PubMed2006

Control of muscle relaxation during anesthesia: a novel approach for clinical routine.

During general anesthesia drugs are administered to provide hypnosis, ensure analgesia, and skeletal muscle relaxation. In this paper, the main components of a newly developed controller for skeletal muscle relaxation are described. Muscle relaxation is controlled by administration of neuromuscular blocking agents. The degree of relaxation is assessed by supramaximal train-of-four stimulation of the ulnar nerve and measuring the electromyogram response of the adductor pollicis muscle. For closed-loop control purposes, a physiologically based pharmacokinetic and pharmacodynamic model of the neuromuscular blocking agent mivacurium is derived. The model is used to design an observer-based state feedback controller. Contrary to similar automatic systems described in the literature this controller makes use of two different measures obtained in the train-of-four measurement to maintain the desired level of relaxation. The controller is validated in a clinical study comparing the performance of the controller to the performance of the anesthesiologist. As presented, the controller was able to maintain a preselected degree of muscle relaxation with excellent precision while minimizing drug administration. The controller performed at least equally well as the anesthesiologist.

Anesthetics, General↗
PubMed1975

Etonitazine-induced rigidity and its antagonism by centrally acting muscle relaxants.

Some narcotic drugs have been reported to produce increases in muscle tone in rats. In our laboratory we have found that etonitazine produces a 'lead-pipe' rigidity of the trunk and limb musculature. The reported studies were conducted to characterize etonitazine-induced rigidity more fully, to compare the degree of rigidity with that produced by morphine, codeine and methadone, and to assess the sensitivity of this rigidity to centrally acting muscle relaxants. Of the 4 narcotics tested, etonitazine was far more potent than methadone or morphine for producing rigidity; codeine did not produce peak rigidity comparable to the other 3 narcotics. Etonitazine-induced rigidity occurs at a supraspinal level since the effect was prevented by spinal transsection. Etonitazine-induced rigidity was prevented by the narcotic antagonists cyclazocine, pentazocine and naloxone but not by the serotonin depletor, p-chlorophenylalanine. Etonitazine-induced rigidity was antagonized by centrally acting muscle relaxants, including diazepam, methocarbamol, carisoprodol and zoxazolamine; in agreement with their relative clinical muscle relaxant potencies, diazepam is the most potent antagonist of etonitazine-induced rigidity.

Analgesics, Opioid↗
PubMed2006

Neurosedative and muscle-relaxant activities of ethyl acetate extract of Baphia nitida AFZEL.

The sedative, anxiolytic and muscle-relaxant effects of the ethyl acetate leaf extract of Baphia nitida (BN) was investigated in intact mice, using the hole-board head-dip test for exploratory behavioural effect, elevated plus maze (EPM) and Y-maze (YM) models of anxiety; chimney, inclined screen, traction and climbing tests for muscle-relaxant effects. In each of these tests, BN (100-400mg/kg, p.o.), diazepam (1mg/kg, i.p.) or distilled water (10ml/kg, p.o.) was administered, 30 or 60min before performing the tests in mice. For exploratory behavioural test, number of head-dip within 15min was counted. For EPM and YM tests, the cumulative time spent in open and closed arms was recorded within 5min. In the muscle-relaxant tests, mice were subjected to modified models such as chimney, inclined screen, traction and climbing tests. BN produced a significant (P<0.05) dose-related decrease in exploratory behaviour in the head-dip test and prolongation of cumulative time spent in open arms of both EPM and YM. BN did not show any significant effect in the chimney and traction tests, but produced significant, dose-dependent muscle relaxation in the inclined screen and climbing tests. Furthermore, BN (200-1200microg/ml) non-competitively shifted the curves of acetylcholine contractions of the toad Rectus abdominis muscle to the right. Oral doses of BN (0.1-20g/kg) did not produce mortality, but the LD(50) when given intraperitoneally, was 645.65mg/kg. Results suggest that the leaf extract of Baphia nitida has sedative, anxiolytic and skeletal muscle-relaxant effects and support its neurosedative use in traditional African medicine.

Animals↗
PubMed1986

Age-related decrease in beta adrenergic receptor-mediated vascular smooth muscle relaxation.

Beta adrenergic receptor-mediated vascular smooth muscle relaxation decreases with increasing age. We have examined the mechanism responsible for this phenomenon using rat mesenteric arteries from young (5-6 weeks) and older (10-12 months) rats. The beta adrenergic agonist isoproterenol produced a dose-dependent relaxation of serotonin-constricted mesenteric artery rings from young rats, whereas the maximal ability of isoproterenol to relax arterial rings from the older rats was found to be reduced markedly (92.7 vs. 27.6%, P less than .0001). The relaxation responses caused by acetylcholine and nitroglycerin, which appear to act independently of cyclic AMP (cAMP), are similar in the two groups. The loss in responsiveness of the mesenteric artery to isoproterenol was not explained by a change in beta receptor number in the vessels (29 +/- 4 in young rats vs. 31 +/- 7 fmol/mg of protein in the older rats). The maximal stimulation of cAMP accumulation by isoproterenol was lower in the older vessels; forskolin activated cAMP accumulation equally in the two groups. However, the vessels from the older rats were less sensitive to forskolin-induced vascular relaxation. Also, the ability of dibutyryl cAMP to promote vascular relaxation was diminished in the older vessels. These data suggest that the diminished cAMP accumulation in older vessels in response to isoproterenol might not necessarily in itself explain completely the reduced physiological response and that an additional defect in the beta adrenergic-mediated relaxation in the vascular smooth muscle of older rats may lie at the level of cAMP-dependent protein kinase activation or more distally.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Long-lasting muscle relaxant activity of eperisone hydrochloride after percutaneous administration in rats.

Potency and duration of muscle relaxant activity of eperisone hydrochloride were examined after percutaneous administration in the intercollicular decerebrated rat rigidity model and compared to those of eperisone after intravenous injection. A continuous movement was loaded on the hindlimb of the rat model to maintain stable rigidity. The tonus of the hindlimb was recorded by EMG from the triceps surae and was quantified by using the public domain NIH Image program. Eperisone ointment administered percutaneously showed significant muscle relaxant activity at 8.4 cm2 (4.2 mg of eperisone)/rat. The effect was dose-dependent and lasted over 60 min. Intravenously injected eperisone showed significant activity at 1.25 mg/kg, but the decrease of tone was lost within 30 min after injection. Plasma eperisone levels were monitored in the same model, and they were well correlated to the dosage. These results suggest that percutaneously administered eperisone is absorbed efficiently and shows potent and long-lasting muscle relaxant activity.

Administration, Cutaneous↗
PubMed2000

Influence of heme oxygenase inhibitors on the basal tissue enzymatic activity and smooth muscle relaxation of internal anal sphincter.

We examined the actions of different heme oxygenase (HO) inhibitors on the basal HO activity in the opossum internal anal sphincter (IAS), rectum, and liver tissues and the IAS smooth muscle relaxation in response to nonadrenergic noncholinergic (NANC) nerve stimulation and different agonists. All the tissues examined were found to have significant levels of basal HO activity. Among different HO inhibitors, tin protoporphyrin IX (SnPP IX) was found to be most selective in inhibiting the HO activity in the IAS smooth muscle. Conversely, in the liver, all the HO inhibitors except SnPP IX caused significant inhibition of HO activity. Consistent with HO activity inhibition, the IAS smooth muscle relaxations caused by NANC nerve stimulation and vasoactive intestinal polypeptide also were inhibited by zinc protoporphyrin IX and SnPP IX. Zinc protoporphyrin IX also caused a significant attenuation of the IAS smooth muscle relaxation caused by isoproterenol. The IAS smooth muscle relaxation caused by nitric oxide was not significantly modified by any of the HO inhibitors. The data show the presence of HO activity in the IAS and other gastrointestinal tissues. The differential attenuation of HO activity by different HO inhibitors in the IAS smooth muscle and liver confirms the presence of different isozymes of HO in different tissues. Suppression of basal HO activity and the IAS smooth muscle relaxation induced by NANC nerve stimulation or VIP but not NO suggest that some of the stimuli that cause IAS smooth muscle relaxation may involve HO activity.

Anal Canal↗
PubMed1983

Role of cyclic AMP in adrenergically-induced tracheal muscle relaxation.

Studies were performed on the isolated bovine tracheal muscle preparation to assess the possible role of adenosine 3',5'-cyclic monophosphate (cyclic AMP) in adrenergically-induced smooth muscle relaxation. Isoproterenol, epinephrine, terbutaline and soterenol were found to relax the tracheal muscle and to increase its cyclic AMP content. The two events generally paralleled one another when analyzed in terms of dose-response and time-response relationships. Propranolol antagonized the relaxation and the increase in cyclic AMP produced by isoproterenol. However, other findings suggested that there may not be a cause and effect relationship between the biochemical and mechanical responses. Thus, salbutamol and carbuterol failed to increase muscle cyclic AMP even in concentrations which produced maximum relaxation. Additionally, butoxamine and H35/25 antagonized the biochemical response but had additive effects (instead of antagonistic effects) on the mechanical response to isoproterenol. Furthermore, it was observed that low concentrations of H35/25 produced tracheal muscle relaxation associated with an increase in tissue cyclic AMP; however, use of a high concentration of H35/25 paradoxically resulted in autoblockade of the increase in cyclic AMP but not the smooth muscle relaxation.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

[Autocontrol of muscle relaxation with vecuronium].

The optimal conditions for maintaining desired levels of muscle relaxation with vecuronium are obtained by means of the continuous infusion (I.V.) technique. A frequent correction of the infusion flow is required, since it is impossible to predict the exact amount for the muscle relaxant in single case. In order to overcome such limits the authors propose a very feasible infusion system for the self-control of muscle relaxation; furthermore they positively consider its possible daily clinical application.

Aged↗
PubMed2000

Evaluating the effectiveness of progressive muscle relaxation in reducing the aggressive behaviors of mentally handicapped patients.

This article reports the results of a study on the evaluation of the effectiveness of muscle relaxation training in reducing aggressive behavior in mentally handicapped patients (MHPs). A pretest and posttest study design was used. Findings showed that there was a reduction of 14.7% of aggressive behavior in the subjects after the muscle relaxation training. Muscle relaxation training appeared to be effective in reducing the frequency of some aggressive behaviors. The strengths and limitations of using muscle relaxation training in reducing aggressive behaviors are discussed.

Adolescent↗