title: Formalin-induced spinal cord calcium/calmodulin-dependent protein kinase II alpha expression is modulated by heme oxygenase in mice.
abstract: 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 IIalpha (CaMKIIalpha) is a key component of long-term potentiation. Here we report alterations in CaMKIIalpha 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 CaMKIIalpha 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 CaMKIIalpha mRNA expression and only a small increase in protein were noted. These findings suggest that time-dependent CaMKIIalpha expression may underlie central sensitization and allodynia induced by hindpaw formalin injection, and that this process is modulated by HO-2.
authors.affiliation: Department of Anesthesiology, Stanford University and Veterans Affairs Palo Alto Health Care System, 112A, 3801 Miranda Avenue, Palo Alto, CA 94304, USA.
authors.forename: De-Yong
authors.initials: DY
authors.lastname: Liang
authors.forename: Xiangqi
authors.initials: X
authors.lastname: Li
authors.forename: J David
authors.initials: JD
authors.lastname: Clark
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D005557:Formaldehyde / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010147:Pain Measurement / Q000379:methods; D021122:Protein Subunits / Q000096:biosynthesis* / Q000235:genetics; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology*
chemical_list: D021122:Protein Subunits; D005557:Formaldehyde; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517671:Camk2a protein, mouse