Progress in neurobiology
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Progress in neurobiology · Jun 1993
ReviewAntinociception induced by alpha-2-adrenoceptor agonists, with special emphasis on medetomidine studies.
Alpha-2-adrenoceptor agonists can activate varying antinociceptive mechanisms depending on the dose and the route of administration, although the main site for their antinociceptive effect in physiological pain conditions seems to be the spinal dorsal horn. In this paper the investigations on the underlying mechanisms are reviewed, with particular emphasis on novel studies using a highly selective and potent alpha-2-adrenoceptor agonist medetomidine. In behavioral studies alpha-2-adrenoceptor agonists, including medetomidine, produce antinociception following systemic administration or local application to the spinal cord. ⋯ Thus, the higher sensitivity of supraspinal neuronal responses and their behavioral correlates to the antinoceptive effect of medetomidine obviously reflects the cumulative effect of medetomidine at several areas along the polysynaptic pathway to the rostral parts of the brain. Paradoxically, the response of immediate early genes in the medial thalamic neurons is only slightly, influenced by antinociceptive doses of medetomidine. Alpha-2-adrenoceptors have significant interactions with other receptors (e.g. opioid, serotonin and muscarine) in producing antinociception at the spinal cord level.