Activation of spinal phosphatidylinositol 3-kinase/protein kinase B mediates pain behavior induced by plantar incision in mice

Abstract

The etiology of postoperative pain may be different from antigen-induced inflammatory pain and neuropathic pain. However, central neural plasticity plays a key role in incision pain. It is also known that phosphatidylinositol 3-kinase (PI3K) and protein kinase B/Akt (PKB/Akt) are widely expressed in laminae I-IV of the spinal horn and play a critical role in spinal central sensitization. In the present study, we explored the role of PI3K and Akt in incision pain behaviors. Plantar incision induced a time-dependent activation of spinal PI3K-p110γ and Akt, while activated Akt and PI3K-p110γ were localized in spinal neurons or microglias, but not in astrocytes. Pre-treatment with PI3K inhibitors, wortmannin or LY294002 prevented the activation of Akt brought on by plantar incision in a dose-dependent manner. In addition, inhibition of spinal PI3K signaling pathway prevented pain behaviors (dose-dependent) and spinal Fos protein expression caused by plantar incision. These data demonstrated that PI3K signaling mediated pain behaviors caused by plantar incision in mice.

Keywords: Center sensitization; Fos; Incisional pain; Phosphatidylinositol 3-kinase; Protein kinase B.