Reversal of morphine antinociceptive tolerance by acute spinal inhibition of Ca(2+)/calmodulin-dependent protein kinase II.
It has been reported that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) can modulate opioid tolerance via its action on learning and memory. In this study, we examine if CaMKII can directly affect opioid tolerance. We found that spinal CaMKII activity was increased in rats tolerant to morphine. In these rats, acute spinal administration of 2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine) (KN93), a CaMKII inhibitor, was able to reverse the already-established antinociceptive tolerance. These results suggest that CaMKII may directly promote opioid tolerance.
Wang
Zaijie Jim
ZJ
Department of Biopharmaceutical Sciences, University of Illinois, 833 South Woods Street, Chicago, IL 60612, USA. zjwang@uic.edu
Tang
Lei
L
Xin
Lili
L
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004361:Drug Tolerance; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000201:enzymology; D013449:Sulfonamides / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D000701:Analgesics, Opioid; D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D009020:Morphine; D013449:Sulfonamides; C425780:KN 92; C072105:KN 93; D000096926:Benzenesulfonamides