Electroacupuncture inhibits phosphorylation of spinal phosphatidylinositol 3-kinase/Akt in a carrageenan-induced inflammatory rat model

We investigated the changes of pain-related spinal signaling pathway after electroacupuncture (EA) stimulation in a carrageenan-induced rat model. EA stimulation (2 Hz, 1 mA) was needle-delivered for 30 min at acupoints corresponding to Zusanli and Sanyinjiao 3 h after carrageenan injection. Thermal and mechanical sensitivity of the hindpaw induced by carrageenan was strongly inhibited by EA stimulation. Phosphorylation of extracellular signal-regulated kinase, phosphatidylinositol 3-kinase (PI3K), Akt, and cAMP response element-binding protein (CREB) were examined in the L4-5 segments of the spinal cord by Western blot analysis 4 h and 5 h after carrageenan injection. Phosphorylation of Akt and especially PI3K were significantly induced by carrageenan-induction, but these expressions were markedly inhibited by EA stimulation. CREB phosphorylation showed a similar, but insignificant, pattern as like PI3k/Akt. Immunohistochemical analyses confirmed that phosphorylation of PI3K and Akt showed a similar pattern as Western blotting and were observed in most neurons and a few astrocytes. EA and PI3K inhibitor synergistically inhibited carrageenan-induced hyperalgesia. These results reveal that both neuronal PI3K and Akt may play an important role in EA-induced antinociception via inactivation in an inflammatory pain model.

► Hyperalgesia induced by carrageenan was strongly inhibited by EA treatment.
► PI3K/Akt activation were significantly induced by carrageenan injection.
► Carrageenan-induced PI3K/Akt activations were markedly inhibited by EA treatment.
► EA and PI3K inhibitor showed a synergistic effect of antinociception.
► Neuronal PI3K/Akt play an important role in EA-induced antinociception.