[Which way for the administration of alpha 2-adrenergic agents to obtain the best analgesia?]

Abstract

Mechanisms of the analgesic actions of alpha 2-adrenergic agonists are likely related to various modulating systems of nociceptive neurotransmission, especially those dependent on opiate receptors. Analgesic action of alpha 2-adrenergic agonists implies alpha 2-adrenergic receptors, strategically located on the dorsal horn neurones of the spinal cord to inhibit the release of substance P in response to peripheral stimuli. However, these receptors are included in the control that supraspinal sites exert via the descending medullospinal noradrenergic pathway. Because of its high lipophilic structure, alpha 2-adrenergic agonist can easily penetrate into the central nervous system, reproducing the effects of activation of medullospinal noradrenergic pathway. Alpha 2-adrenergic agonists have been found to be efficient in human pain treatment after systemic, spinal or troncular administration, but there were few randomized clinical studies comparing analgesia potency and adverse effects of either systemic or regional administrations. Clonidine added to local anaesthetic agents increases the analgesic effects in a greater extent than systemic administration of similar dose, probably because this effect depends on the local clonidine concentration. Extradural administration of clonidine is also more efficient than systemic administration, at least when high doses are injected. This superiority is questionable when low-dose clonidine is used. Adverse effects are quite similar in both systemic and spinal routes. Invasiveness of extradural route may be considered in regard to the gain which may be expected in analgesia efficiency.