Background: Abnormalities in peripheral nerves and dorsal root ganglia are noticed in the early stage of experimentally provoked diabetic neuropathy. Enzyme calcium/calmodulin-dependent protein kinase II (CaMKII) may have a modulating role in diabetic neuropathy because of its role in calcium homeostasis.
Methods: A model of type 1 diabetes mellitus (DM1) was induced with 55 mg/kg of the streptozotocin and for DM2 induction a combination of high-fat diet and low-dose streptozotocin (35 mg/kg) was used. Pain-related behavior was analyzed using thermal and mechanical stimuli. Two weeks and 2 months after induction of diabetes rats were euthanized, and the expression of CaMKII and its isoforms in the dorsal root ganglia were analyzed using immunofluorescence.
Results: Both types of diabetes were successfully induced, as confirmed by hyperglycemia. Increased pain-related behavior became evident in DM1 rats in 2 weeks after diabetes induction, but not in DM2 rats. The expression of total CaMKII and the phosphorylated α isoform of CaMKII increased in DM1 animals concurrently with pain-related behavior. Expression of α, β, γ, and δ isoforms in DM1 animals and expression of total CaMKII and all of its analyzed isoforms in DM2 animals remained unchanged.
Conclusions: Our findings may indicate involvement of CaMKII in transmission of nociceptive input early in DM1, but not in DM2. CaMKII may be a suitable pharmacological target for diabetic neuropathy.