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

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

BMC Neuroscience

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

• Bing Xu, 
• Cheng Mo, 
• Chengmei Lv, 
• Susu Liu, 
• Jun Li, 
• Jieying Chen, 
• Yanhong Wei, 
• Hongwei An, 
• Li Ma & 
• Xuehai Guan 

BMC Neurosciencevolume 20, Article number: 36 (2019) | Download Citation

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.