Abstract
BackgroundPostoperative 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.MethodsA 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.ResultsPost-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.ConclusionsWe 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.
Highlights
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
Post‐surgical inhibition of Phosphatidylinositol 3-kinase (PI3K) significantly attenuated mechanical allodynia, thermal hyperalgesia, and cumulative pain scores induced by plantar incision in male mice Plantar incision activated PI3K pathway, and pre-surgical treatment with PI3K inhibitor wortmannin or LY294002 prevented pain behavior induced by plantar incision [5]
Post‐surgical inhibition of PI3K mildly attenuated mechanical allodynia, thermal hyperalgesia, and cumulative pain scores induced by plantar incision in female mice Sex differences have been identified in clinical pain conditions, and influences of these differences on pain and analgesia have become a topic of preclinical and clinical interest
Summary
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. Our previous research revealed that pre-surgical inhibition of spinal PI3K alleviated the pain behavior induced by plantar incision in mice. We have previously shown that pre-surgical inhibition of spinal PI3K alleviated the pain behavior induced by plantar incision in mice [5]. Post-operative analgesia is more critical than pre-operative analgesia; whether post-surgical inhibition of PI3K could attenuate the POP is unknown, and the plausible mechanisms involved remain elusive. To verify these possibilities, we explored the analgesic effect of post-surgical inhibition of PI3K and the underlying mechanism by combining behavioral and molecular biological methods
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