丝裂原活化蛋白激酶在糖尿病神经病理性疼痛中枢敏化和外周敏化中作用的研究进展
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摘要
丝裂原活化蛋白激酶(MAPKs)是一组包括细胞外信号调节激酶1/2、c-Jun氨基端激酶1/2/3、p38亚型(α,β,γ和δ)和细胞外信号调节激酶5的丝/苏氨酸蛋白激酶,能够介导增殖、分化、凋亡、免疫、炎症等一系列细胞活动。痛觉敏化是一种中枢和外周伤害性感受器的重塑机制。大量研究显示,MAPKs在糖尿病动物模型的脊髓和背根神经节中广泛激活,在糖尿病神经病理性疼痛(DNP)中枢敏化和外周敏化中发挥了重要的作用。此外,一些药物也可通过抑制中枢和外周神经系统中MAPKs的激活来缓解DNP。本文主要总结了MAPKs在DNP中枢和外周敏化中作用的研究进展。
Mitogen-activated protein kinases( MAPKs) are Ser/Thr kinases consisting of extracellular regulated protein kinases( ERK) 1/2,c-Jun N-terminal kinase 1/2/3,p38 isoforms( α,β,γ,and δ),and ERK5,which mediate a range of cellular activities including proliferation,differentiation,apoptosis,immunity,and inflammation. Pain sensitization is a remodeling mechanism of central and peripheral nociceptor. A growing number of evidences have indicated that MAPKs are extensively activated in the spinal dorsal cord and dorsal root ganglions in the animal models of diabetic neuropathic pain( DNP) and play an important role in the central and peripheral sensitization of DNP. In addition,some drugs can alleviate DNP by suppressing MAPKs activation of central and peripheral nervous system. This article summarizes the research progress of MAPKs in central and peripheral sensitization of DNP.
Mitogen-activated protein kinases( MAPKs) are Ser/Thr kinases consisting of extracellular regulated protein kinases( ERK) 1/2,c-Jun N-terminal kinase 1/2/3,p38 isoforms( α,β,γ,and δ),and ERK5,which mediate a range of cellular activities including proliferation,differentiation,apoptosis,immunity,and inflammation. Pain sensitization is a remodeling mechanism of central and peripheral nociceptor. A growing number of evidences have indicated that MAPKs are extensively activated in the spinal dorsal cord and dorsal root ganglions in the animal models of diabetic neuropathic pain( DNP) and play an important role in the central and peripheral sensitization of DNP. In addition,some drugs can alleviate DNP by suppressing MAPKs activation of central and peripheral nervous system. This article summarizes the research progress of MAPKs in central and peripheral sensitization of DNP.
引文
[1]中华医学会糖尿病学分会.中国2型糖尿病防治指南(2017年版)[J].中华糖尿病杂志,2018,10(1):4-67. DOI:10. 3760/cma. j. issn. 1674-5809. 2018. 01. 003.
[2]申帮利,曹红,李军.丝裂原活化蛋白激酶与糖尿病性神经病理性疼痛[J].国际麻醉学与复苏杂志,2008,29(3):228-231.
[3] Tomlinson DR,Gardiner NJ. Diabetic neuropathies:compo-nents of etiology[J]. J Peripher Nerv Syst,2008,13(2):112-121. DOI:10. 1111/j. 1529-8027. 2008. 00167. x.
[4] Kim EK,Choi EJ. Pathological roles of MAPK signaling path-ways in human diseases[J]. Biochim Biophys Acta,2010,1802(4):396-405. DOI:10. 1016/j. bbadis. 2009. 12. 009.
[5] Peti W,Page R. Molecular basis of MAP kinase regulation[J]. Protein Sci,2013,22(12):1698-1710. DOI:10. 1002/pro. 2374.
[6] Arthur JS,Ley SC. Mitogen-activated protein kinases in in-nate immunity[J]. Nat Rev Immunol,2013,13(9):679-692. DOI:10. 1038/nri3495.
[7] D’Mello R,Dickenson AH. Spinal cord mechanisms of pain[J]. Br J Anaesth,2008,101(1):8-16. DOI:10. 1093/bja/aen088.
[8] Woolf CJ,Ma Q. Nociceptors-noxious stimulus detectors[J].Neuron,2007,55(3):353-364. DOI:10. 1016/j. neuron. 2007.07. 016.
[9] Chen WH,Chang YT,Chen YC,et al. Spinal protein ki-nase C/extracellular signal-regulated kinase signal pathwaymediates hyperalgesia priming[J]. Pain,2018,159(5):907-918. DOI:10. 1097/j. pain. 0000000000001162.
[10] Sanna MD,Galeotti N. The HDAC1/c-JUN complex is es-sential in the promotion of nerve injury-induced neuropathicpain through JNK signaling[J]. Eur J Pharmacol,2018,825:99-106. DOI:10. 1016/j. ejphar. 2018. 02. 034.
[11]朱春燕,何超杰,姚明,等.骨癌痛大鼠脊髓趋化因子受体2与P38丝裂原活化蛋白激酶信号通路的关系[J].中华医学杂志,2018,98(4):289-293. DOI:10. 3760/cma. j. issn. 0376-2491. 2018. 04. 010.
[12] Meng XW,Gao JL,Zuo JL,et al. Toll-like receptor-4/p38MAPK signaling in the dorsal horn contributes to P2X4 recep-tor activation and BDNF over-secretion in cancer inducedbone pain[J]. Neurosci Res,2017,125:37-45. DOI:10.1016/j. neures. 2017. 06. 006.
[13] Ciruela A,Dixon AK,Bramwell S,et al. Identification ofMEK1 as a novel target for the treatment of neuropathic pain[J]. Br J Pharmacol,2003,138(5):751-756. DOI:10.1038/sj. bjp. 0705103.
[14] Daulhac L,Mallet C,Courteix C,et al. Diabetes-inducedmechanical hyperalgesia involves spinal mitogen-activated pro-tein kinase activation in neurons and microglia via N-methyl-D-aspartate-dependent mechanisms[J]. Mol Pharmacol,2006,70(4):1246-1254. DOI:10. 1124/mol. 106. 025478.
[15] Tsuda M,Ueno H,Kataoka A,et al. Activation of dorsalhorn microglia contributes to diabetes-induced tactile allodyniavia extracellular signal-regulated protein kinase signaling[J].Glia,2008,56(4):378-386. DOI:10. 1002/glia. 20623.
[16] Xu X,Chen H,Ling BY,et al. Extracellular signal-regula-ted protein kinase activation in spinal cord contributes to painhypersensitivity in a mouse model of type 2 diabetes[J].Neurosci Bull,2013,30(1):53-66. DOI:10. 1007/s12264-013-1387-y.
[17] Daulhacl L,Maffrel V,Malletl C,et al. Phosphorylation ofspinal N-methyl-d-aspartate receptor NR1 subunits by extra-cellular signal-regulated kinase in dorsal horn neurons and mi-croglia contributes to diabetes-induced painful neuropathy[J].Eur J Pain,2011,15(2):169-161. DOI:10. 1016/j. ejpain.2010. 06. 003.
[18] Dang JK,Wu Y,Cao H,et al. Establishment of a rat mod-el of type II diabetic neuropathic pain[J]. Pain Med,2014,15(4):637-646. DOI:10. 1111/pme. 12387_1.
[19]胡涵,赵佳伊,曹红,等.脊髓MCP-1-ERK-KIF17/NR2B信号通路在大鼠2型糖尿病神经痛维持中的作用[J].中华麻醉学杂志,2015,35(5):563-566. DOI:10. 3760/cma. j. issn. 0254-1416. 2015. 05. 011.
[20]周林,袁超,史小婷,等.姜黄素对2型糖尿病神经病理性痛大鼠脊髓背角及背根神经节p-ERK和p-CREB表达的影响[J].中华麻醉学杂志,2013,33(8):928-931.DOI:10. 3760/cma. j. issn. 0254-1416. 2013. 08. 006.
[21] Ogata Y,Nemoto W,Nakagawasai O,et al. Involvement ofspinal angiotensinⅡsystem in streptozotocin-induced diabeticneuropathic pain in mice[J]. Mol Pharmacol,2016,90(3):205-213. DOI:10. 1124/mol. 116. 104133.
[22] Sweitzer SM,Medicherla S,Almirez R,et al. Antinocicep-tive action of a p38alpha MAPK inhibitor,SD-282,in a dia-betic neuropathy model[J]. Pain,2004,109(3):409-419.DOI:10. 1016/j. pain. 2004. 02. 016.
[23] Cheng KI,Wang HC,Chuang YT,et al. Persistent me-chanical allodynia positively correlates with an increase in ac-tivated microglia and increased P-p38 mitogen-activated pro-tein kinase activation in streptozotocin-induced diabetic rats[J]. Eur J Pain,2013,18(2):162-173. DOI:10. 1002/j.1532-2149. 2013. 00356. x.
[24]柯昌斌,罗向红,全守波,等. MK-801在大鼠糖尿病神经病理性疼痛中的作用及其对p38MAPK的影响[J].广东医学,2009,30(12):1792-1794. DOI:10. 13820/j. cnki.gdyx. 2009. 12. 034.
[25]柯昌斌,黄晓霞,李元涛,等.氯胺酮对糖尿病神经痛大鼠p38丝裂原活化蛋白激酶表达的影响[J].郧阳医学院学报,2008(5):395-397.
[26] Suzuki N,Hasegawa-Moriyama M,Takahashi Y,et al. Li-docaine attenuates the development of diabetic-induced tactileallodynia by inhibiting microglial activation[J]. Anesth Analg,2011,113(4):941-946. DOI:10. 1213/ANE. 0b013e31822827a2.
[27] Toth CC,Jedrzejewski NM,Ellis CL,et al. Cannabinoid-mediated modulation of neuropathic pain and microglial accu-mulation in a model of murine typeⅠdiabetic peripheral neuro-pathic pain[J]. Mol Pain,2010,6:16. DOI:10. 1186/1744-8069-6-16.
[28] Sun JS,Yang YJ,Zhang YZ,et al. Minocycline attenuatespain by inhibiting spinal microglia activation in diabetic rats[J]. Mol Med Rep,2015,12(2):2677-2682. DOI:10. 3892/mmr. 2015. 3735.
[29]马长华,杨欢,罗振中.电针对糖尿病神经病理性疼痛大鼠痛阈及脊髓p38MAPK表达的影响[J].现代医院,2016,16(10):1432-1433,1436. DOI:10. 3969/j. issn. 1671-332X. 2016. 10. 008.
[30]杨欢,郑小兰,罗振中.电针刺激对糖尿病神经病理性疼痛大鼠脊髓p38MAPK的影响[J].广东医学,2016,37(17):2555-2557. DOI:10. 13820/j. cnki. gdyx. 20160923.001.
[31] Ortmann KL,Chattopadhyay M. Decrease in neuroimmuneactivation by HSV-mediated gene transfer of TNFαsoluble re-ceptor alleviates pain in rats with diabetic neuropathy[J].Brain Behav Immun,2014,41:144-151. DOI:10. 1016/j.bbi. 2014. 05. 009.
[32] Ton BH,Chen Q,Gaina G,et al. Activation profile of dor-sal root ganglia Iba-1(+)macrophages varies with the typeof lesion in rats[J]. Acta Histochem,2013,115(8):840-850. DOI:10. 1016/j. acthis. 2013. 04. 007.
[33] Cheng HT,Dauch JR,Oh SS,et al. p38 mediates me-chanical allodynia in a mouse model of type 2 diabetes[J].Mol Pain,2010,6:28. DOI:10. 1186/1744-8069-6-28.
[34] Pabbidi RM,Cao DS,Parihar A,et al. Direct role of strep-tozotocin in inducing thermal hyperalgesia by enhanced ex-pression of transient receptor potential vanilloid 1 in sensoryneurons[J]. Mol Pharmacol,2008,73(3):995-1004. DOI:10. 1124/mol. 107. 041707.
[35] Chattopadhyay M,Mata M,Fink DJ. Continuous-opioid re-ceptor activation reduces neuronal voltage-gated sodium chan-nel(NaV1. 7)levels through activation of protein kinase Cin painful diabetic neuropathy[J]. J Neurosci,2008,28(26):6652-6658. DOI:10. 1523/jneurosci. 5530-07. 2008.
[36] Khan S,Choi RJ,Lee J,et al. Attenuation of neuropathicpain and neuroinflammatory responses by a pyranocoumarinderivative,anomalin in animal and cellular models[J]. EurJ Pharmacol,2016,774:95-104. DOI:10. 1016/j. ejphar.2016. 02. 008.
[37] Thakur V,Gonzalez M,Pennington K,et al. Viral vectormediated continuous expression of interleukin-10 in DRG alle-viates pain in type 1 diabetic animals[J]. Mol Cell Neuros-ci,2016,72:46-53. DOI:10. 1016/j. mcn. 2016. 01. 006.
[38]闫哲,周小丽,王汉兵,等.糖尿病周围神经痛大鼠脊髓背角JNK水平的变化[J].中国现代医学杂志,2010,20(14):2150-2152+2157.
[39]郑昌健,胡涵,曹红,等. JNK/MCP-1信号通路在姜黄素抗糖尿病神经病理性疼痛中的作用[J].中国病理生理杂志,2014,30(11):1941-1945. DOI:10. 3969/j. issn. 1000-4718. 2014. 11. 004.
[40]申帮利,余相地,曹红,等.姜黄素对大鼠糖尿病神经病理性痛的效应[J].中华麻醉学杂志,2009,29(7):626-629. DOI:10. 3760/cma. j. issn. 0254-1416. 2009. 07. 013.
[41] Middlemas AB,Agthong S,Tomlinson DR. Phosphorylationof c-Jun N-terminal kinase(JNK)in sensory neurones of di-abetic rats, with possible effects on nerve conduction andneuropathic pain:prevention with an aldose reductase inhibi-tor[J]. Diabetologia,2006,49(3):580-587. DOI:10. 1007/s00125-005-0133-z.
[42]冯荧娣,倪桂莲,汪利琼,等.加巴喷丁对糖尿病性神经痛大鼠机械痛敏和背根神经节神经元JNK及p-JNK表达的影响[J].医学研究杂志,2013,42(10):68-72.
[2]申帮利,曹红,李军.丝裂原活化蛋白激酶与糖尿病性神经病理性疼痛[J].国际麻醉学与复苏杂志,2008,29(3):228-231.
[3] Tomlinson DR,Gardiner NJ. Diabetic neuropathies:compo-nents of etiology[J]. J Peripher Nerv Syst,2008,13(2):112-121. DOI:10. 1111/j. 1529-8027. 2008. 00167. x.
[4] Kim EK,Choi EJ. Pathological roles of MAPK signaling path-ways in human diseases[J]. Biochim Biophys Acta,2010,1802(4):396-405. DOI:10. 1016/j. bbadis. 2009. 12. 009.
[5] Peti W,Page R. Molecular basis of MAP kinase regulation[J]. Protein Sci,2013,22(12):1698-1710. DOI:10. 1002/pro. 2374.
[6] Arthur JS,Ley SC. Mitogen-activated protein kinases in in-nate immunity[J]. Nat Rev Immunol,2013,13(9):679-692. DOI:10. 1038/nri3495.
[7] D’Mello R,Dickenson AH. Spinal cord mechanisms of pain[J]. Br J Anaesth,2008,101(1):8-16. DOI:10. 1093/bja/aen088.
[8] Woolf CJ,Ma Q. Nociceptors-noxious stimulus detectors[J].Neuron,2007,55(3):353-364. DOI:10. 1016/j. neuron. 2007.07. 016.
[9] Chen WH,Chang YT,Chen YC,et al. Spinal protein ki-nase C/extracellular signal-regulated kinase signal pathwaymediates hyperalgesia priming[J]. Pain,2018,159(5):907-918. DOI:10. 1097/j. pain. 0000000000001162.
[10] Sanna MD,Galeotti N. The HDAC1/c-JUN complex is es-sential in the promotion of nerve injury-induced neuropathicpain through JNK signaling[J]. Eur J Pharmacol,2018,825:99-106. DOI:10. 1016/j. ejphar. 2018. 02. 034.
[11]朱春燕,何超杰,姚明,等.骨癌痛大鼠脊髓趋化因子受体2与P38丝裂原活化蛋白激酶信号通路的关系[J].中华医学杂志,2018,98(4):289-293. DOI:10. 3760/cma. j. issn. 0376-2491. 2018. 04. 010.
[12] Meng XW,Gao JL,Zuo JL,et al. Toll-like receptor-4/p38MAPK signaling in the dorsal horn contributes to P2X4 recep-tor activation and BDNF over-secretion in cancer inducedbone pain[J]. Neurosci Res,2017,125:37-45. DOI:10.1016/j. neures. 2017. 06. 006.
[13] Ciruela A,Dixon AK,Bramwell S,et al. Identification ofMEK1 as a novel target for the treatment of neuropathic pain[J]. Br J Pharmacol,2003,138(5):751-756. DOI:10.1038/sj. bjp. 0705103.
[14] Daulhac L,Mallet C,Courteix C,et al. Diabetes-inducedmechanical hyperalgesia involves spinal mitogen-activated pro-tein kinase activation in neurons and microglia via N-methyl-D-aspartate-dependent mechanisms[J]. Mol Pharmacol,2006,70(4):1246-1254. DOI:10. 1124/mol. 106. 025478.
[15] Tsuda M,Ueno H,Kataoka A,et al. Activation of dorsalhorn microglia contributes to diabetes-induced tactile allodyniavia extracellular signal-regulated protein kinase signaling[J].Glia,2008,56(4):378-386. DOI:10. 1002/glia. 20623.
[16] Xu X,Chen H,Ling BY,et al. Extracellular signal-regula-ted protein kinase activation in spinal cord contributes to painhypersensitivity in a mouse model of type 2 diabetes[J].Neurosci Bull,2013,30(1):53-66. DOI:10. 1007/s12264-013-1387-y.
[17] Daulhacl L,Maffrel V,Malletl C,et al. Phosphorylation ofspinal N-methyl-d-aspartate receptor NR1 subunits by extra-cellular signal-regulated kinase in dorsal horn neurons and mi-croglia contributes to diabetes-induced painful neuropathy[J].Eur J Pain,2011,15(2):169-161. DOI:10. 1016/j. ejpain.2010. 06. 003.
[18] Dang JK,Wu Y,Cao H,et al. Establishment of a rat mod-el of type II diabetic neuropathic pain[J]. Pain Med,2014,15(4):637-646. DOI:10. 1111/pme. 12387_1.
[19]胡涵,赵佳伊,曹红,等.脊髓MCP-1-ERK-KIF17/NR2B信号通路在大鼠2型糖尿病神经痛维持中的作用[J].中华麻醉学杂志,2015,35(5):563-566. DOI:10. 3760/cma. j. issn. 0254-1416. 2015. 05. 011.
[20]周林,袁超,史小婷,等.姜黄素对2型糖尿病神经病理性痛大鼠脊髓背角及背根神经节p-ERK和p-CREB表达的影响[J].中华麻醉学杂志,2013,33(8):928-931.DOI:10. 3760/cma. j. issn. 0254-1416. 2013. 08. 006.
[21] Ogata Y,Nemoto W,Nakagawasai O,et al. Involvement ofspinal angiotensinⅡsystem in streptozotocin-induced diabeticneuropathic pain in mice[J]. Mol Pharmacol,2016,90(3):205-213. DOI:10. 1124/mol. 116. 104133.
[22] Sweitzer SM,Medicherla S,Almirez R,et al. Antinocicep-tive action of a p38alpha MAPK inhibitor,SD-282,in a dia-betic neuropathy model[J]. Pain,2004,109(3):409-419.DOI:10. 1016/j. pain. 2004. 02. 016.
[23] Cheng KI,Wang HC,Chuang YT,et al. Persistent me-chanical allodynia positively correlates with an increase in ac-tivated microglia and increased P-p38 mitogen-activated pro-tein kinase activation in streptozotocin-induced diabetic rats[J]. Eur J Pain,2013,18(2):162-173. DOI:10. 1002/j.1532-2149. 2013. 00356. x.
[24]柯昌斌,罗向红,全守波,等. MK-801在大鼠糖尿病神经病理性疼痛中的作用及其对p38MAPK的影响[J].广东医学,2009,30(12):1792-1794. DOI:10. 13820/j. cnki.gdyx. 2009. 12. 034.
[25]柯昌斌,黄晓霞,李元涛,等.氯胺酮对糖尿病神经痛大鼠p38丝裂原活化蛋白激酶表达的影响[J].郧阳医学院学报,2008(5):395-397.
[26] Suzuki N,Hasegawa-Moriyama M,Takahashi Y,et al. Li-docaine attenuates the development of diabetic-induced tactileallodynia by inhibiting microglial activation[J]. Anesth Analg,2011,113(4):941-946. DOI:10. 1213/ANE. 0b013e31822827a2.
[27] Toth CC,Jedrzejewski NM,Ellis CL,et al. Cannabinoid-mediated modulation of neuropathic pain and microglial accu-mulation in a model of murine typeⅠdiabetic peripheral neuro-pathic pain[J]. Mol Pain,2010,6:16. DOI:10. 1186/1744-8069-6-16.
[28] Sun JS,Yang YJ,Zhang YZ,et al. Minocycline attenuatespain by inhibiting spinal microglia activation in diabetic rats[J]. Mol Med Rep,2015,12(2):2677-2682. DOI:10. 3892/mmr. 2015. 3735.
[29]马长华,杨欢,罗振中.电针对糖尿病神经病理性疼痛大鼠痛阈及脊髓p38MAPK表达的影响[J].现代医院,2016,16(10):1432-1433,1436. DOI:10. 3969/j. issn. 1671-332X. 2016. 10. 008.
[30]杨欢,郑小兰,罗振中.电针刺激对糖尿病神经病理性疼痛大鼠脊髓p38MAPK的影响[J].广东医学,2016,37(17):2555-2557. DOI:10. 13820/j. cnki. gdyx. 20160923.001.
[31] Ortmann KL,Chattopadhyay M. Decrease in neuroimmuneactivation by HSV-mediated gene transfer of TNFαsoluble re-ceptor alleviates pain in rats with diabetic neuropathy[J].Brain Behav Immun,2014,41:144-151. DOI:10. 1016/j.bbi. 2014. 05. 009.
[32] Ton BH,Chen Q,Gaina G,et al. Activation profile of dor-sal root ganglia Iba-1(+)macrophages varies with the typeof lesion in rats[J]. Acta Histochem,2013,115(8):840-850. DOI:10. 1016/j. acthis. 2013. 04. 007.
[33] Cheng HT,Dauch JR,Oh SS,et al. p38 mediates me-chanical allodynia in a mouse model of type 2 diabetes[J].Mol Pain,2010,6:28. DOI:10. 1186/1744-8069-6-28.
[34] Pabbidi RM,Cao DS,Parihar A,et al. Direct role of strep-tozotocin in inducing thermal hyperalgesia by enhanced ex-pression of transient receptor potential vanilloid 1 in sensoryneurons[J]. Mol Pharmacol,2008,73(3):995-1004. DOI:10. 1124/mol. 107. 041707.
[35] Chattopadhyay M,Mata M,Fink DJ. Continuous-opioid re-ceptor activation reduces neuronal voltage-gated sodium chan-nel(NaV1. 7)levels through activation of protein kinase Cin painful diabetic neuropathy[J]. J Neurosci,2008,28(26):6652-6658. DOI:10. 1523/jneurosci. 5530-07. 2008.
[36] Khan S,Choi RJ,Lee J,et al. Attenuation of neuropathicpain and neuroinflammatory responses by a pyranocoumarinderivative,anomalin in animal and cellular models[J]. EurJ Pharmacol,2016,774:95-104. DOI:10. 1016/j. ejphar.2016. 02. 008.
[37] Thakur V,Gonzalez M,Pennington K,et al. Viral vectormediated continuous expression of interleukin-10 in DRG alle-viates pain in type 1 diabetic animals[J]. Mol Cell Neuros-ci,2016,72:46-53. DOI:10. 1016/j. mcn. 2016. 01. 006.
[38]闫哲,周小丽,王汉兵,等.糖尿病周围神经痛大鼠脊髓背角JNK水平的变化[J].中国现代医学杂志,2010,20(14):2150-2152+2157.
[39]郑昌健,胡涵,曹红,等. JNK/MCP-1信号通路在姜黄素抗糖尿病神经病理性疼痛中的作用[J].中国病理生理杂志,2014,30(11):1941-1945. DOI:10. 3969/j. issn. 1000-4718. 2014. 11. 004.
[40]申帮利,余相地,曹红,等.姜黄素对大鼠糖尿病神经病理性痛的效应[J].中华麻醉学杂志,2009,29(7):626-629. DOI:10. 3760/cma. j. issn. 0254-1416. 2009. 07. 013.
[41] Middlemas AB,Agthong S,Tomlinson DR. Phosphorylationof c-Jun N-terminal kinase(JNK)in sensory neurones of di-abetic rats, with possible effects on nerve conduction andneuropathic pain:prevention with an aldose reductase inhibi-tor[J]. Diabetologia,2006,49(3):580-587. DOI:10. 1007/s00125-005-0133-z.
[42]冯荧娣,倪桂莲,汪利琼,等.加巴喷丁对糖尿病性神经痛大鼠机械痛敏和背根神经节神经元JNK及p-JNK表达的影响[J].医学研究杂志,2013,42(10):68-72.