Correlation Engine 2.0
Clear Search sequence regions


Alpha(2A)-Adrenoceptors mediate the antinociceptive effects of alpha(2)-adrenoceptor agonists in mice, and analgesic synergism between noradrenergic and opioidergic mechanisms has been reported to be lacking in mice devoid of functional alpha(2A)-adrenoceptors. We investigated whether the antinociceptive actions of opioid agonists with different efficacy would be altered in mice with targeted inactivation of the alpha(2A)-adrenoceptor gene (alpha(2A)-KO mice). The antinociceptive effects of fentanyl, morphine, buprenorphine and tramadol were assessed using conventional tail-flick and hot-plate assays. Antinociceptive responses to fentanyl were unaltered in the alpha(2A)-KO animals. Morphine analgesia was slightly accentuated in the tail-flick test. The naloxone-sensitive antinociceptive responses to both tested weak partial agonists were very markedly accentuated in both tests. For example, after 40 mg/kg tramadol administration, the tramadol-induced prolongation of tail-flick latency was 86+/-6% of the maximal possible effect (MPE) in alpha(2A)-KO and 22+/-2% of MPE in control mice; prolongation of hot-plate latency was 93+/-5% of MPE in alpha(2A)-KO mice and 8+/-2% of MPE in the controls (P<0.001 for both). The effects of alpha(2A)-KO were mimicked by pretreatment of wild-type control mice with the alpha(2)-adrenoceptor antagonists, atipamezole and yohimbine; the apparent efficacy of tramadol and buprenorphine now approached that of morphine and fentanyl. Other behavioural effects of the tested opioid agonists were not similarly influenced by alpha(2A)-KO. Antagonists of alpha(2A)-adrenoceptors may offer a novel mechanism to augment the antinociceptive actions of partial opioid agonists.

Citation

Umit Kazim Ozdoğan, Janne Lähdesmäki, Mika Scheinin. The analgesic efficacy of partial opioid agonists is increased in mice with targeted inactivation of the alpha2A-adrenoceptor gene. European journal of pharmacology. 2006 Jan 4;529(1-3):105-13

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 16325800

View Full Text