Roles And Mechanisms Of Calcium/calmodulin-dependent Serine Protein Kinase In Dorsal Root Ganglion Of Rats With Diabetic Neuropathic Pain

Background: Calcium/Calmodulin-dependent serine protein kinase(CASK) is mainly expressed in central nervous system, which is recognized as a neuronal scaffolding protein. Whereas, the role of CASK in diabetic neuropathic pain remains unclear. The aim of this research is to explore whether CASK plays a role in hyperalgesia of rats with diabetics mellitus(DM).Methods: DM was induced by a single intraperitoneal injection of streptozocin(STZ). Di I was injected into hindpaw for retrogradely labeling the soma of hindpaw-specific dorsal root ganglion(DRG) neurons. Expression of CASK and P2 X receptors were measured by Western blot analysis. Nociceptive behaviror was assessed by quantify standards of hind paw withdrawal threshold(PWT) by means of Von Frey Filament stimulation and paw withdrawal latency(PWL) by means of heat stimulation.Results:(1) STZ treatment induced diabetic neuropathic pain in DM rats. Behavioral score of PWT and PWL is aberrant in DM group.(2) Expression of CASK and P2X2 receptor(purinergic receptor P2 X, ligand-gated ion channel, 2) are upregulated in DM group when compared with control group.(3) Intrathecal injection of CASK sh RNA suppressed CASK and P2X2 receptor expression in DM group and reduced ATP-evoked current density in hindpaw-specific DRG neurons.(4) Importantly, intrathecal injection of CASK sh RNA attenuated behavioral score of PWT and PWL in DM group with diabetic neuropathic pain.Conclusions: These results suggest that CASK/P2 X signaling pathway is likely participated in the process of diabetic neuropathic pain formation.