Reversal of morphine antinociceptive tolerance by acute spinal inhibition of Ca(2+)/calmodulin-dependent protein kinase II

Zaijie Jim Wang; Lei Tang; Lili Xin

doi:10.1016/s0014-2999(03)01484-5

Reversal of morphine antinociceptive tolerance by acute spinal inhibition of Ca(2+)/calmodulin-dependent protein kinase II

Eur J Pharmacol. 2003 Mar 28;465(1-2):199-200. doi: 10.1016/s0014-2999(03)01484-5.

Authors

Zaijie Jim Wang¹, Lei Tang, Lili Xin

Affiliation

¹ Department of Biopharmaceutical Sciences, University of Illinois, 833 South Woods Street, Chicago, IL 60612, USA. zjwang@uic.edu

PMID: 12650850
DOI: 10.1016/s0014-2999(03)01484-5

Abstract

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.

MeSH terms

Analgesics, Opioid / pharmacology*
Animals
Benzylamines / pharmacology*
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
Calcium-Calmodulin-Dependent Protein Kinases / metabolism
Drug Tolerance
Enzyme Inhibitors / pharmacology*
Injections, Spinal
Male
Morphine / pharmacology*
Nociceptors / drug effects
Pain / prevention & control
Pain Measurement / methods
Rats
Rats, Sprague-Dawley
Spinal Cord / enzymology
Sulfonamides / pharmacology*

Substances

Analgesics, Opioid
Benzylamines
Enzyme Inhibitors
KN 92
Sulfonamides
KN 93
Morphine
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases