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

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.