Ca2+/calmodulin-dependent protein kinase II alpha is required for the initiation and maintenance of opioid-induced hyperalgesia
Language: 
English
Abstract: 

Repeated administration of opioids not only leads to tolerance and dependence, but also results in nociceptive enhancement called opioid-induced hyperalgesia (OIH). Nociceptive mediators involved in OIH generation remain poorly understood. In the present study, we tested the hypothesis that Ca(2+)/calmodulin-depent protein kinase II (CaMKIIalpha) is critical for OIH. Opioid-induced hyperalgesia was produced by repeated morphine administration or pellet implantation in mice. Correlating with the development of tactile allodynia and thermal hyperalgesia, spinal CaMKIIalpha activity was significantly increased in OIH. KN93, a CaMKII inhibitor, dose- and time-dependently reversed OIH and CaMKII activation without impairing locomotor coordination. To elucidate the specific CaMKII isoform involved, we targeted CaMKIIalpha by using small interfering RNA and demonstrated that knockdown of spinal CaMKIIalpha attenuated OIH. Furthermore, morphine failed to induce OIH in CaMKIIalpha(T286A) point mutant mice, although wild-type littermate mice developed robust OIH after repeated treatments with morphine. These data implicate, for the first time, an essential role of CaMKIIalpha as a cellular mechanism leading to and maintaining opioid-induced hyperalgesia.

Author(s): 
Chen, Yan
Yang, Cheng
Wang, Zaijie Jim
Item Type: 
Journal Article
Publication Title: 
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience
Journal Abbreviation: 
J. Neurosci.
Publication Date: 
Jan 6, 2010
Publication Year: 
2010
Pages: 
38-46
Volume: 
30
Issue: 
1
ISSN: 
1529-2401
DOI: 
10.1523/JNEUROSCI.4346-09.2010
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 20053885 PMCID: PMC2821163

Turabian/Chicago Citation

Yan Chen, Cheng Yang and Zaijie Jim Wang. Jan 6, 2010. "Ca2+/calmodulin-dependent protein kinase II alpha is required for the initiation and maintenance of opioid-induced hyperalgesia." The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 30: 1: 38-46. 10.1523/JNEUROSCI.4346-09.2010.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1523/JNEUROSCI.4346-09.2010 | issn = 1529-2401 | volume = 30 | pages = 38-46 | last = Chen | first = Yan | coauthors = Yang, Cheng, Wang, Zaijie Jim | title = Ca2+/calmodulin-dependent protein kinase II alpha is required for the initiation and maintenance of opioid-induced hyperalgesia | journal = The Journal of Neuroscience: The Official Journal of the Society for Neuroscience | date = Jan 6, 2010 | pmid = | pmc = }} </ref>