Electroacupuncture alleviates streptozotocin-induced diabetic neuropathic pain via suppressing phosphorylated CaMKII in rats

Diabetic neuropathic pain (DNP) is a frequent complication of diabetes. Calcium/calmodulin-dependent protein kinase II alpha (CaMKII alpha), a multi-functional serine/threonine kinase subunit, is mainly located in the surface layer of the spinal cord dorsal horn (SCDH) and the primary sensory neurons in dorsal root ganglion (DRG). Numerous studies have indicated electroacupuncture (EA) takes effect in various kinds of pain. In this research, we explored whether CaMKII alpha on rats' SCDH and DRG participated in DNP and further explored the mechanisms underlying the analgesic effects of EA. The DNP model in rats was successfully established by intraperitoneal injection of streptozotocin. Certain DNP rats were treated with intrathecal injections of KN93, a CaMKII antagonist, and some of the DNP rats received EA intervention. The general conditions, behaviors, the expressions of CaMKII alpha and phosphorylated CaMKII alpha (p-CaMKII alpha) were evaluated. DNP rats' paw withdrawal threshold was reduced and the expressions of p-CaMKII alpha in SCDH and DRG were upregulated compared with the Normal group, while the level of CaMKII alpha showed no significance. KN93 attenuated DNP rats' hyperalgesia and reduced the expressions of p-CaMKII alpha. We also found EA attenuated the hyperalgesia of DNP rats and reduced the expressions of p-CaMKII alpha. The above findings suggest that p-CaMKII alpha in SCDH and DRG is involved in DNP. The analgesic effect of EA in DNP might be related to the downregulation of p-CaMKII alpha expression level. Our study further supports that EA can be an effective clinical treatment for DNP.