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Activation of phosphatidylinositol 3-kinase and protein kinase B/Akt in dorsal root ganglia and spinal cord contributes to the neuropathic pain induced by spinal nerve ligation in rats.
Exp Neurol. 2007 Aug; 206(2):269-79.EN

Abstract

Several lines of evidence indicate that phosphatidylinositol 3-kinase (PI3K) and PI3K-protein kinase B/Akt (PKB/Akt) signal pathway mediate the pain hypersensitivity induced by intradermal injection of capsaicin or nerve growth factor. However, the role of PI3K and PI3K-PKB/Akt signal pathway activation in neuropathic pain is still unclear. Using L5 spinal nerve ligation (L5 SNL) and immunohistochemistry, we found that the numbers of phospho-PKB/Akt-immunoreactive (p-PKB/Akt IR) positive neurons were significantly increased in ipsilateral L5 dorsal root ganglia (DRG) and adjacent L4 DRG started at 12 h after surgery and maintained to the 3rd day. Meanwhile, L5 SNL also induced an increased expression of p-PKB/Akt in ipsilateral L5 spinal dorsal horn. Double immunofluorescence staining showed that p-PKB/Akt expressed entirely in DRG neurons, especially in IB4-positive neurons. Intrathecal injection of PI3K inhibitor wortmannin or LY294002 and PKB/Akt inhibitor Akt inhibitor IV or (-)-Deguelin, started before L5 SNL, reduced the behavioral signs of neuropathic pain. Intraperitoneal injection of wortmannin or (-)-Deguelin as above also reduced the pain hypersensitivity. Post-treatment with wortmannin, started at the 1st day or the 3rd day after L5 SNL, decreased abnormal pain behaviors. Whereas the inhibitory effect of Akt inhibitor IV on established neuropathic pain was observed only in those rats that received the drug treatment started at the 1st day. Immunohistochemistry revealed that intrathecal injection of wortmannin significantly inhibited the activation of PKB/Akt in L5 DRG and L5 spinal cord. The data suggested that PI3K and PI3K-PKB/Akt signal pathway activation might contribute to the development of neuropathic pain.

Authors+Show Affiliations

Department of Physiology and Department of Neurobiology, Medical School of Zhengzhou University, 40 Daxue Rd., Zhengzhou, 450052 PR China. jtxu@zzu.edu.cnNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17628541

Citation

Xu, Ji-Tian, et al. "Activation of Phosphatidylinositol 3-kinase and Protein Kinase B/Akt in Dorsal Root Ganglia and Spinal Cord Contributes to the Neuropathic Pain Induced By Spinal Nerve Ligation in Rats." Experimental Neurology, vol. 206, no. 2, 2007, pp. 269-79.
Xu JT, Tu HY, Xin WJ, et al. Activation of phosphatidylinositol 3-kinase and protein kinase B/Akt in dorsal root ganglia and spinal cord contributes to the neuropathic pain induced by spinal nerve ligation in rats. Exp Neurol. 2007;206(2):269-79.
Xu, J. T., Tu, H. Y., Xin, W. J., Liu, X. G., Zhang, G. H., & Zhai, C. H. (2007). Activation of phosphatidylinositol 3-kinase and protein kinase B/Akt in dorsal root ganglia and spinal cord contributes to the neuropathic pain induced by spinal nerve ligation in rats. Experimental Neurology, 206(2), 269-79.
Xu JT, et al. Activation of Phosphatidylinositol 3-kinase and Protein Kinase B/Akt in Dorsal Root Ganglia and Spinal Cord Contributes to the Neuropathic Pain Induced By Spinal Nerve Ligation in Rats. Exp Neurol. 2007;206(2):269-79. PubMed PMID: 17628541.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of phosphatidylinositol 3-kinase and protein kinase B/Akt in dorsal root ganglia and spinal cord contributes to the neuropathic pain induced by spinal nerve ligation in rats. AU - Xu,Ji-Tian, AU - Tu,Hui-Yin, AU - Xin,Wen-Jun, AU - Liu,Xian-Guo, AU - Zhang,Gui-Hong, AU - Zhai,Cai-Hong, Y1 - 2007/06/14/ PY - 2007/01/20/received PY - 2007/05/09/revised PY - 2007/05/10/accepted PY - 2007/7/14/pubmed PY - 2007/9/22/medline PY - 2007/7/14/entrez SP - 269 EP - 79 JF - Experimental neurology JO - Exp Neurol VL - 206 IS - 2 N2 - Several lines of evidence indicate that phosphatidylinositol 3-kinase (PI3K) and PI3K-protein kinase B/Akt (PKB/Akt) signal pathway mediate the pain hypersensitivity induced by intradermal injection of capsaicin or nerve growth factor. However, the role of PI3K and PI3K-PKB/Akt signal pathway activation in neuropathic pain is still unclear. Using L5 spinal nerve ligation (L5 SNL) and immunohistochemistry, we found that the numbers of phospho-PKB/Akt-immunoreactive (p-PKB/Akt IR) positive neurons were significantly increased in ipsilateral L5 dorsal root ganglia (DRG) and adjacent L4 DRG started at 12 h after surgery and maintained to the 3rd day. Meanwhile, L5 SNL also induced an increased expression of p-PKB/Akt in ipsilateral L5 spinal dorsal horn. Double immunofluorescence staining showed that p-PKB/Akt expressed entirely in DRG neurons, especially in IB4-positive neurons. Intrathecal injection of PI3K inhibitor wortmannin or LY294002 and PKB/Akt inhibitor Akt inhibitor IV or (-)-Deguelin, started before L5 SNL, reduced the behavioral signs of neuropathic pain. Intraperitoneal injection of wortmannin or (-)-Deguelin as above also reduced the pain hypersensitivity. Post-treatment with wortmannin, started at the 1st day or the 3rd day after L5 SNL, decreased abnormal pain behaviors. Whereas the inhibitory effect of Akt inhibitor IV on established neuropathic pain was observed only in those rats that received the drug treatment started at the 1st day. Immunohistochemistry revealed that intrathecal injection of wortmannin significantly inhibited the activation of PKB/Akt in L5 DRG and L5 spinal cord. The data suggested that PI3K and PI3K-PKB/Akt signal pathway activation might contribute to the development of neuropathic pain. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/17628541/Activation_of_phosphatidylinositol_3_kinase_and_protein_kinase_B/Akt_in_dorsal_root_ganglia_and_spinal_cord_contributes_to_the_neuropathic_pain_induced_by_spinal_nerve_ligation_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(07)00200-2 DB - PRIME DP - Unbound Medicine ER -