![]() The protocol was approved by the local ethical committee and written informed consent was obtained from the subjects. is the structure of sleep modified in the night after tramadol application)? Materials and methods Subjects is the structure of sleep modified in the night of tramadol application)? Second, what are the medium-term effects of tramadol on sleep structure (i.e. First, what are the short-term effects of tramadol on sleep structure (i.e. The aim of this study was to establish a model to investigate the relative impact of analgesics on sleep structure in man, using standardized and validated methods of polysomnography, and to investigate the effects of tramadol on sleep structure in healthy volunteers without pain. The effect of tramadol on sleep has never been investigated. Norepinephrine and 5-hydroxytryptamine neurons play an important role in inhibiting paradoxical sleep, as was found with antidepressant drugs. It has also been suggested that sleep could be disturbed by inhibiting norepinephrine and 5-hydroxytryptamine neuronal re-uptake. Uncontrolled observations in patients undergoing surgery receiving morphine to treat acute postoperative pain indicated that there may be a rebound in paradoxical sleep some days after the end of morphine administration. These authors postulated that morphine via the mu opioid receptor may inhibit the release of acetylcholine in the reticular formation and that this may inhibit paradoxical sleep. For instance, in cats, microinjection of morphine (an opioid with a high affinity to mu receptors) into the medial pontine reticular formation, a structure playing a key role in regulating paradoxical sleep, significantly inhibited paradoxical sleep and increased the number of apnoeic episodes. There are some data on the effects of opioids on sleep structure from experiments in animals and studies in patients undergoing surgery (i.e. It may be difficult in these patients to differentiate between sleep disturbance caused by pain, by the underlying disease, or by the analgesic treatment. Patients with pain often suffer from sleep disturbances. Compared with morphine it is thought to cause less tolerance, addiction and respiratory depression. Tramadol is used in the treatment of acute and chronic pain. It is a racemic mixture of two enantiomers, (+)tramadol and (–)tramadol and it has been found in vivo and in vitro to have a low but preferential activity at mu opioid receptors, and it also inhibits both norepinephrine and 5-hydroxytryptamine neuronal re-uptake. Tramadol (Tramal ®, Grünenthal) is a centrally acting analgesic drug. With 100 mg, sleep is disturbed in both the night of drug application and in the subsequent night. In healthy volunteers, a single dose of tramadol 50 mg disturbs sleep in the night of drug application. In the placebo-night after tramadol 100 mg (but not after 50 mg) duration of stage 2 sleep was significantly shorter, and duration of stage 4 sleep was significantly longer compared with the predrug placebo-night. Tramadol 100 mg but not 50 mg significantly decreased the duration of paradoxical (rapid eye movement) sleep. Resultsĭuring drug-nights both doses of tramadol significantly increased the duration of stage 2 sleep, and significantly decreased the duration of slow-wave sleep (stage 4). Standardized polysomnography (electroencephalogram, electrooculogram, submental electromyogram) was continuously recorded during placebo- and drug-nights. MethodsĮight healthy volunteers received a placebo (predrug placebo-night), then, in a randomized, double-blind, cross-over fashion a single oral dose of tramadol 50 mg or 100 mg (drug-night), and finally, again a placebo (postdrug placebo-night). We investigated short- and medium-term effects of tramadol on sleep structure. The effects of analgesic drugs on sleep are poorly understood.
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