Formalin-induced spinal cord calcium/calmodulin-dependent protein kinase IIα expression is modulated by heme oxygenase in mice

• Published in: Neuroscience letters Vol. 360; no. 1; pp. 61 - 64
• Main Authors: Liang, De-Yong, Li, Xiangqi, Clark, J.David
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 22.04.2004; Elsevier
• Subjects: Animals; Biological and medical sciences; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases - biosynthesis; Calcium-Calmodulin-Dependent Protein Kinases - genetics; Calcium/calmodulin-dependent kinase II; Central sensitization; Formaldehyde - pharmacology; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Enzymologic - drug effects; Gene Expression Regulation, Enzymologic - physiology; Heme oxygenase; Heme Oxygenase (Decyclizing) - deficiency; Heme Oxygenase (Decyclizing) - genetics; Heme Oxygenase (Decyclizing) - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Pain Measurement - methods; Protein Subunits - biosynthesis; Protein Subunits - genetics; Spinal cord; Spinal Cord - drug effects; Spinal Cord - enzymology; Vertebrates: nervous system and sense organs; Central sensitization; Calcium/calmodulin-dependent kinase II; Spinal cord; Gene expression; Heme oxygenase; Calcium; Enzyme; Transferases; Rodentia; Central nervous system; Oxygenase; Vertebrata; Mammalia; Mouse; Kinase; Protein kinase; Animal; Heme; Oxidoreductases; Calmodulin
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2004.02.050

The injection of formalin into the hindpaws of rats and mice is widely used as a model of inflammatory pain. The allodynia observed in this model is due in part to sensitization of spinal cord dorsal horn neurons, a form of neuroplasticity similar to long-term potentiation in the hippocampus. Ca 2+/calmodulin-dependent kinase type IIα (CaMKIIα) is a key component of long-term potentiation. Here we report alterations in CaMKIIα mRNA and protein expression in spinal cord tissue from wild-type and heme oxygenase type 2 (HO-2) null mutant mice after formalin injection. Behavioral experiments demonstrated a long lived allodynia in wild-type C57Bl/6J mice after hindpaw formalin injection, but less in null mutant mice. Both CaMKIIα mRNA and protein expression were increased in a time-dependent manner in the spinal cords of wild-type mice after formalin injection. Confocal microscopy localized the increased expression to the superficial laminae of the spinal cord dorsal horn. In the HO-2 null mutant mice no significant change in CaMKIIα mRNA expression and only a small increase in protein were noted. These findings suggest that time-dependent CaMKIIα expression may underlie central sensitization and allodynia induced by hindpaw formalin injection, and that this process is modulated by HO-2.