Post-surgical inhibition of phosphatidylinositol 3-kinase attenuates the plantar incision-induced postoperative pain behavior via spinal Akt activation in male mice

• Main Authors: Bing Xu, Cheng Mo, Chengmei Lv, Susu Liu, Jun Li, Jieying Chen, Yanhong Wei, Hongwei An, Li Ma, Xuehai Guan
• Format: Article
• Language: English
• Published: BMC 2019-07-01
• Series: BMC Neuroscience
• Subjects: Postoperative pain; Plantar incision; Phosphatidylinositol 3-kinase; Akt; Spinal dorsal horn
• Online Access: http://link.springer.com/article/10.1186/s12868-019-0521-9

Abstract Background Postoperative pain (POP) is a severe acute pain encountered in patients suffering from an operation, and is less than adequately controlled by the currently available analgesics. Phosphatidylinositol 3-kinase (PI3K) has been reported to have an important role in neuropathic and inflammatory pain. Our previous research revealed that pre-surgical inhibition of spinal PI3K alleviated the pain behavior induced by plantar incision in mice. The aim of this study was to clarify whether post-surgical inhibition of PI3K would attenuate the POP and the underlying mechanisms. Methods A POP model was established by plantar incision in Kunming mice. A behavioral test was performed to determine mechanical allodynia, thermal hyperalgesia, and cumulative pain scores. The spinal Fos was detected by immunohistochemistry. The spinal expression of protein kinase B (Akt) or phosphorylated Akt (pAkt) was explored using western blot. The cellular location of pAkt was determined by immunofluorescence. Results Post-surgical inhibition of PI3K attenuated mechanical allodynia, thermal hyperalgesia, and cumulative pain scores induced by plantar incision significantly in male mice, and mildly in female mice. Post-surgical inhibition of PI3K attenuated the expression of spinal Fos in male mice. Plantar incision induced a time-dependent expression of spinal pAkt in male mice, which was primarily expressed in the spinal dorsal horn, and localized with the neuron and microglia’s marker. Post-surgical inhibition of PI3K attenuated the activation of Akt induced by plantar incision in male mice as well. Conclusions We concluded that post-surgical inhibition of PI3K could attenuate the pain-related behaviors induced by plantar incision, by suppressing the activation of spinal Akt in male mice. This finding might be used in clinical studies to reach a better understanding of POP mechanisms and optimal treatment.