Der Schmerz
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Spinal clonidine interacts with pre- and postsynaptic alpha(2)-adrenoceptors on afferent neurons in the superficial dorsal horn of the spinal cord: it causes analgesia by inhibition of the synaptic and electrotonic neurotransmission of nociceptive impulses. Epidural doses higher than 4 microg/kg have an analgesic onset time of less than 30 min, reduce pain by more than 70 %; these effects last for 4-5 h. ⋯ The haemodynamic side effects mean close supervision is needed during the first hour after epidural application and limit the use of epidural clonidine to patients who are refractory to the analgesic effects of epidural opioid or local anaesthetics. In these patients excellent results can be achieved either with clonidine alone or with a combination of clonidine and an opioid or a local anaesthetic to exploit the additive or supra-additive interactions of these drugs.
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The antinociceptive effect of alpha(2)-adrenoceptor agonists is mediated by activation of descending inhibiting noradrenergic systems, which modulates 'wide-dynamic-range' neurones. Furthermore, they inhibit the liberation of substance P and endorphines and activate serotoninergic neurones. Despite this variety of antinociceptive actions, there is still little experience with alpha(2)-adrenoceptor agonists as therapeutic agents for use in chronic pain syndromes. ⋯ In isolated cases clonidine has been administered epidurally at a dose of 1500 microg/day for almost 5 months without evidence for any histotoxic property of clonidine. Side effects often observed during administration of alpha(2)-adrenoceptor agonists are dry mouth, sedation, hypotension and bradycardia. Therapeutic interventions are usually not required.