HMGB1 and diabetes mellitus: Furthermore, Zhao and colleagues (2016), demonstrated that calmodulin-dependent protein kinase IV (CaMKIV), a protein kinase involved in neuropathic pain, and HMGB-1 are upregulated in the dorsal root ganglia of rats treated with STZ, a substance used to induce diabetes and neuropathic pain.109 Inhibition of phosphorylated CaMKIV (pCaMKIV) decreases HMGB-1 levels and reduces thermal hyperalgesia and mechanical allodynia in diabetic rats, confirming the role of HMGB-1 in neuropathic pain.110