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

Xu, Bing; Guan, Xue-Hai; Yu, Jianchun; Lv, Jing; Zhang, Hongxing; Fu, Qiaochu; Xiang, Hongyu; Bu, Huilian; Shi, Dai; Shu, Bin; Qin, Li-Sheng; Manyande, Anne; Tian, Yuan

doi:10.1016/j.expneurol.2014.02.019

Cited by 40 publications

(37 citation statements)

References 82 publications

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“…It was shown that plantar incision (the animal model of post-operative pain) induced a time-dependent activation of PI3K/Akt pathway in spinal cord and DRG. At the spinal cord level this activation was colocalized with the neuronal and microglial markers, but not with astrocytes [202]. …”

Section: Phosphoinositide 3-kinase (Pi3k)/aktmentioning

confidence: 99%

Targeting the Microglial Signaling Pathways: New Insights in the Modulation of Neuropathic Pain

Popiołek-Barczyk¹,

Mika

2016

CMC

145

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The microglia, once thought only to be supporting cells of the central nervous system (CNS), are now recognized to play essential roles in many pathologies. Many studies within the last decades indicated that the neuro-immune interaction underlies the generation and maintenance of neuropathic pain. Through a large number of receptors and signaling pathways, the microglial cells communicate with neurons, astrocytes and other cells, including those of the immune system. A disturbance or loss of CNS homeostasis causes rapid responses of the microglia, which undergo a multistage activation process. The activated microglia change their cell shapes and gene expression profiles, which induce proliferation, migration, and the production of pro- or antinociceptive factors. The cells release a large number of mediators that can act in a manner detrimental or beneficial to the surrounding cells and can indirectly alter the nociceptive signals. This review discusses the most important microglial intracellular signaling cascades (MAPKs, NF-κB, JAK/STAT, PI3K/Akt) that are essential for neuropathic pain development and maintenance. Our objective was to identify new molecular targets that may result in the development of powerful tools to control the signaling associated with neuropathic pain.

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Section: Phosphoinositide 3-kinase (Pi3k)/aktmentioning

confidence: 99%

Targeting the Microglial Signaling Pathways: New Insights in the Modulation of Neuropathic Pain

Popiołek-Barczyk¹,

Mika

2016

CMC

145

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“…Phosphoinositide 3-kinase (PI3K) has been demonstrated to be essential in the development and maintenance of chronic pain [11,12]. It is a lipid kinase that phosphorylates the D3 position of the inositol ring of phosphoinositide and thereby generates intracellular signaling molecules such as phosphorylation of Akt (pAkt) at Thr308 and Ser473 [13]. The mammalian PI3K signaling family is categorized into three classes (I, II, III) according to their structure and substrate specificity [14,15].…”

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confidence: 99%

PI3K/Akt Pathway: A Potential Therapeutic Target for Chronic Pain

Chen

Zhou

Liu

et al. 2017

CPD

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Chronic pain is among the most disabling and costly disorders, with prevalence ranging from 10% to 55%. However, current therapeutic strategies for chronic pain are unsatisfactory due to our poor understanding of its mechanisms. Thus, novel therapeutic targets need to be found in order to improve these patients' quality of life. PI3K and its downstream Akt are widely expressed in the spinal cord, particularly in the laminae I-IV of the dorsal horn, where nociceptive C and Aδ fibers of primary afferents principally terminate. Recent studies have demonstrated their critical roles in the development and maintenance of chronic pain. In this review, we summarized the roles and mechanisms of PI3K/Akt pathway in the progression of chronic pain through sciatic nerve injury, diabetic neuropathy, spinal cord injury, bone cancer, opioid tolerance, or opioid-induced hyperalgesia.

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“…Animals were placed in individual plastic boxes with a metal mesh floor and allowed to habituate for 30 min prior to tests. Mechanical paw withdrawal threshold was measured by an ascending series of von Frey filaments (0.6, 1.0, 1.4, 2.0, 4.0, 6.0, 8.0, 10.0 and 15.0 g; Stoelting, Wood Dale, IL, USA) as previously reported (14,17,18). The filaments were applied perpendicular to mid-plantar surface of the left hind paw.…”

Section: Methodsmentioning

confidence: 99%

Anti-rheumatic drug iguratimod protects against cancer-induced bone pain and bone destruction in a rat model

Sun

Zhang

et al. 2017

Oncology Letters

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The bone is one of the most common sites of metastasis in patients with cancer. Current treatments for bone metastases include bisphosphonates, denosumab, non-steroidal anti-inflammatory drugs and analgesics, but each of them has certain limitations. Cytokines and mediators released from various cells in the bone microenvironment may drive a vicious cycle of osteolytic bone metastases. Iguratimod (T-614), a novel disease-modifying anti-rheumatic drug, has demonstrated therapeutic effects by suppressing the production of inflammatory cytokines in rats and patients with rheumatoid arthritis. Therefore, the current study evaluated the hypothesis that iguratimod may protect against cancer-induced bone pain and bone metastasis in a rat model. For this purpose, rats inoculated with Walker 256 cells were treated with iguratimod from days 11–17 post-surgery. Mechanical paw withdrawal thresholds and expression levels of phosphorylated extracellular signal-related kinase (pERK) and c-Fos in the spinal cord were investigated to detect changes in bone pain. Bone destruction levels were detected using X-rays, hematoxylin and eosin and tartrate-resistant acid phosphatase staining. The results revealed that mechanical paw withdrawal thresholds and the expression levels of pERK and c-Fos declined in a dose-dependent manner in rats treated with iguratimod, and bone destruction severity was also reduced. These findings may provide important new insights into the treatment of bone metastasis symptoms.

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

Cited by 40 publications

References 82 publications

Targeting the Microglial Signaling Pathways: New Insights in the Modulation of Neuropathic Pain

Targeting the Microglial Signaling Pathways: New Insights in the Modulation of Neuropathic Pain

PI3K/Akt Pathway: A Potential Therapeutic Target for Chronic Pain

Anti-rheumatic drug iguratimod protects against cancer-induced bone pain and bone destruction in a rat model

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