Casein kinase 2 (CK2) is a widely expressed
protein kinase. Over the last several years a long list of
protein substrates has evolved, many of which have proven or hypothesized roles in nociceptive signal transmission. However, CK2 has not itself been demonstrated to participate in nociception prior to this time. We set out to test the hypothesis that spinal CK2 regulates nociception using several
pain models. Our first studies focused on the ability of the selective CK2 inhibitors
4,5,6,7-tetrabromobenzotriazole (TBBT) and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (
DRB) to reduce
formalin-stimulated
pain behaviors in mice. Both phases of the response to subcutaneous
formalin were strongly inhibited by intrathecal administration of TBBT or
DRB in dose-dependent fashion. Likewise, using the complete
Freund's adjuvant (CFA) model of chronic inflammatory
pain, TBBT was observed to strongly reduce
mechanical allodynia. The inhibition of spinal CK2 with either inhibitor did not, however, alter withdrawal latencies in the hotplate thermal
pain model while intrathecal
morphine was very effective. Immunohistochemical studies demonstrated all three known CK2 subunits, alpha, alpha' and beta to be expressed in spinal cord tissue as did real-time PCR experiments. While
mRNA levels for each of the subunits was transiently enhanced after
formalin or CFA hindpaw injection, overall spinal cord
protein levels were not elevated in a sustained fashion. Our results indicate that CK2 participates in inflammatory nociception both in the acute and chronic phases. Simple changes in the abundance of spinal CK2 subunits do not likely underlie these phenomena, however.