Involvement of Protein Kinase B/Akt in Analgesic Effect of Dexmedetomidine on Neuropathic Pain

Li, Shuangshuang; Zhang, Wei-Shi; Yang, Jiale; Xiong, Yang; Zhang, Yu‐Qiu; Xu, Hua

doi:10.1111/cns.12100

Cited by 9 publications

(9 citation statements)

References 12 publications

(19 reference statements)

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“…Only four articles involved this outcome, and the subjectivity of different patients and the type of surgery may cause the significant heterogeneity. The mechanism of the analgesic effect of dexmedetomidine remains unclear and may be related to the involvement of Protein Kinase B/Akt .…”

Section: Discussionmentioning

confidence: 99%

Effects of Intravenous and Intrathecal Dexmedetomidine in Spinal Anesthesia: A Meta‐Analysis

et al. 2013

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Section: Discussionmentioning

confidence: 99%

Effects of Intravenous and Intrathecal Dexmedetomidine in Spinal Anesthesia: A Meta‐Analysis

et al. 2013

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“…These valid analgesic properties were also found in varied pain conditions, such as chronic constrictive injury (CCI) of the sciatic nerve-induced neuropathic pain [25], [56] and pH 5.0 PBS-induced acute inflammatory pain in mice [31], as well as bone cancer induced-pain in rats [57].…”

Section: Discussionmentioning

confidence: 99%

Inhibiting Spinal Neuron-Astrocytic Activation Correlates with Synergistic Analgesia of Dexmedetomidine and Ropivacaine

Yin

Zhang

et al. 2014

PLoS ONE

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BackgroundThis study aims to identify that intrathecal (i.t.) injection of dexmedetomidine (Dex) and ropivacaine (Ropi) induces synergistic analgesia on chronic inflammatory pain and is accompanied with corresponding “neuron-astrocytic” alterations.MethodsMale, adult Sprague-Dawley rats were randomly divided into sham, control and i.t. medication groups. The analgesia profiles of i.t. Dex, Ropi, and their combination detected by Hargreaves heat test were investigated on the subcutaneous (s.c.) injection of complete Freund adjuvant (CFA) induced chronic pain in rat and their synergistic analgesia was confirmed by using isobolographic analysis. During consecutive daily administration, pain behavior was daily recorded, and immunohistochemical staining was applied to investigate the number of Fos-immunoreactive (Fos-ir) neurons on hour 2 and day 1, 3 and 7, and the expression of glial fibrillary acidic protein (GFAP) within the spinal dorsal horn (SDH) on day 1, 3, 5 and 7 after s.c. injection of CFA, respectively, and then Western blot to examine spinal GFAP and β-actin levels on day 3 and 7.Resultsi.t. Dex or Ropi displayed a short-term analgesia in a dose-dependent manner, and consecutive daily administrations of their combination showed synergistic analgesia and remarkably down-regulated neuronal and astrocytic activations indicated by decreases in the number of Fos-ir neurons and the GFAP expression within the SDH, respectively.Conclusioni.t. co-delivery of Dex and Ropi shows synergistic analgesia on the chronic inflammatory pain, in which spinal “neuron-astrocytic activation” mechanism may play an important role.

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“…Akt was discovered as a major regulator of cell cycle in the 1990s ( Brazil et al, 2004 ). Spinal cord expression of Akt and its downstream effectors suggests their involvement in the transmission and modulation of noxious information ( Sun et al, 2006 , 2007 ; Xu et al, 2007 , 2011 ; Guedes et al, 2008 ; Choi et al, 2012 ; Duan et al, 2012 ; Kay et al, 2013 ; Li et al, 2013 ; Hung et al, 2014 ; Xu J.T. et al, 2014 ; Zhang et al, 2014 , 2019 ; Guan et al, 2015 ; Kondo et al, 2018 ; Liu et al, 2019 ; Xing et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies indicate that activation of the serine/threonine protein kinase, Akt (also known as PKB), contributes to pain-related behaviors induced by various kinds of stimuli, including capsaicin, BDNF, and chronic nerve constriction ( Sun et al, 2006 , 2007 ; Xu et al, 2007 , 2011 ; Guedes et al, 2008 ; Choi et al, 2012 ; Duan et al, 2012 ; Kay et al, 2013 ; Li et al, 2013 ; Hung et al, 2014 ; Xu B. et al, 2014 ; Zhang et al, 2014 ). Akt plays an important role in various key biological functions such as cell cycle processes, apoptosis, proliferation, survival, and growth in response to cytokines or growth factors ( Manning and Cantley, 2007 ; Yang et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

“…Akt plays an important role in various key biological functions such as cell cycle processes, apoptosis, proliferation, survival, and growth in response to cytokines or growth factors ( Manning and Cantley, 2007 ; Yang et al, 2011 ). Importantly, Akt is widely expressed in the spinal cord, particularly in the dorsal root ganglia (DRG) and laminae I-IV of the spinal dorsal horn, a key site for processing nociceptive information ( Sun et al, 2006 , 2007 ; Xu et al, 2007 , 2011 ; Guedes et al, 2008 ; Choi et al, 2012 ; Duan et al, 2012 ; Kim et al, 2012 ; Li et al, 2013 ; Kay et al, 2013 ; Hung et al, 2014 ; Xu J.T. et al, 2014 ; Zhang et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

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Role of Spinal Cord Akt-mTOR Signaling Pathways in Postoperative Hyperalgesia Induced by Plantar Incision in Mice

Liu

Wei

et al. 2020

Front. Neurosci.

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Poor postoperative pain (POP) control increases perioperative morbidity, prolongs hospitalization days, and causes chronic pain. However, the specific mechanism(s) underlying POP is unclear and the identification of optimal perioperative treatment remains elusive. Akt and mammalian target of rapamycin (mTOR) are expressed in the spinal cord, dorsal root ganglion, and sensory axons. In this study, we explored the role of Akt and mTOR in pain-related behaviors induced by plantar incision in mice. Plantar incision activated spinal Akt and mTOR in a dose-dependent manner. Pre-treatment with Akt inhibitors intrathecally prevented the activation of mTOR dose-dependently. In addition, blocking the Akt-mTOR signaling cascade attenuated pain-related behaviors and spinal Fos protein expression induced by plantar incision. Our observations demonstrate that Akt-mTOR might be a potential therapeutic target for the treatment of POP.

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Involvement of Protein Kinase B/Akt in Analgesic Effect of Dexmedetomidine on Neuropathic Pain

Cited by 9 publications

References 12 publications

Effects of Intravenous and Intrathecal Dexmedetomidine in Spinal Anesthesia: A Meta‐Analysis

Effects of Intravenous and Intrathecal Dexmedetomidine in Spinal Anesthesia: A Meta‐Analysis

Inhibiting Spinal Neuron-Astrocytic Activation Correlates with Synergistic Analgesia of Dexmedetomidine and Ropivacaine

Role of Spinal Cord Akt-mTOR Signaling Pathways in Postoperative Hyperalgesia Induced by Plantar Incision in Mice

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