药学学报, 2020, 55(2): 201-207
引用本文:
文苾蕊, 张志玲, 陈乃宏. Wnt信号通路在神经病理性疼痛中的作用及机制研究进展[J]. 药学学报, 2020, 55(2): 201-207.
WEN Bi-rui, ZHANG Zhi-ling, CHEN Nai-hong. Research progress on the role and mechanism of Wnt signaling pathway in neuropathic pain[J]. Acta Pharmaceutica Sinica, 2020, 55(2): 201-207.

Wnt信号通路在神经病理性疼痛中的作用及机制研究进展
文苾蕊1,2, 张志玲2, 陈乃宏1,2
1. 湖南中医药大学药学院, 湖南省中药饮片标准化及功能工程技术研究中心, 湖南 长沙 410208;
2. 中国医学科学院、北京协和医学院药物研究所, 神经科学中心, 北京 100050
摘要:
神经病理性疼痛(neuropathic pain,NP)作为一种慢性疼痛综合征,严重危害患者生活质量,且发病机制复杂,临床疗法有限,极易复发。越来越多的报道发现Wnt信号通路与神经病理性疼痛的发生和发展密切相关。因此,对Wnt信号通路的进一步研究可能为探索NP的发病机制及发现有效治疗手段提供新思路。本文就Wnt信号通路在神经病理性疼痛中的作用及机制进行综述。
关键词:    神经病理性疼痛      Wnt信号通路      Wnt/β-catenin      痛觉过敏      痛觉超敏     
Research progress on the role and mechanism of Wnt signaling pathway in neuropathic pain
WEN Bi-rui1,2, ZHANG Zhi-ling2, CHEN Nai-hong1,2
1. Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China;
2. Neuroscience Center, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
Neuropathic pain (NP), as a kind of chronic pain syndrome, seriously endangers the quality of life of patients, and the pathogenesis is complex, clinical treatment is limited, and it is easy to relapse. More and more reports have found that Wnt signaling pathway is closely related to the occurrence and development of neuropathic pain. Therefore, further study of the Wnt signaling pathway may provide useful ideas for exploring the pathogenesis of NP and discovering effective treatment methods. This article reviews the role and mechanism of Wnt signaling pathway in neuropathic pain.
Key words:    neuropathic pain    Wnt signaling pathway    Wnt/β-catenin    hyperpathia    allodynia   
收稿日期: 2019-08-02
DOI: 10.16438/j.0513-4870.2019-0624
基金项目: 国家自然科学基金项目(81730096,81503275,81560685);国家中医药管理局科研项目(ZYBZH-Y-HUN-24);湖南省中药饮片标准化及功能工程技术研究中心项目(2016TP2008,BG201701);湖南省中医药一流学科项目(201803).
通讯作者: 陈乃宏,Tel/Fax:86-10-63165177,E-mail:chennh@imm.ac.cn
Email: chennh@imm.ac.cn
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参考文献:
[1] Zilliox LA. Neuropathic pain[J]. Continuum (Minneap Minn), 2017, 23:512-532.
[2] Fernandes V, Sharma D, Vaidya S, et al. Cellular and molecular mechanisms driving neuropathic pain:recent advancements and challenges[J]. Expert Opin Ther Targets, 2018, 22:131-142.
[3] St John Smith E. Advances in understanding nociception and neuropathic pain[J]. J Neurol, 2018, 265:231-238.
[4] Zhao B, Pan Y, Xu H, et al. Hyperbaric oxygen attenuates neuropathic pain and reverses inflammatory signaling likely via the Kindlin-1/Wnt-10a signaling pathway in the chronic pain injury model in rats[J]. J Headache Pain, 2017, 18:1.
[5] Zhao Y, Zhang L, Wang M, et al. Anxiety specific response and contribution of active hippocampal neural stem cells to chronic pain through Wnt/β-catenin signaling in mice[J]. Front Mol Neurosci, 2018, 11:296.
[6] Zhong JM, Lu YC, Zhang J. Dexmedetomidine reduces diabetic neuropathy pain in rats through the Wnt 10a/β-catenin signaling pathway[J]. Biomed Res Int, 2018, 2018:9043628.
[7] Hussain A, Dar MS, Bano N, et al. Identification of dinactin, a macrolide antibiotic, as a natural product-based small molecule targeting Wnt/β-catenin signaling pathway in cancer cells[J]. Cancer Chemother Pharmacol, 2019, 84:551-559.
[8] Resham K, Sharma SS. Pharmacologic inhibition of porcupine, disheveled, and β-catenin in Wnt signaling pathway ameliorates diabetic peripheral neuropathy in rats[J]. J Pain, 2019, 20:1338-1352.
[9] Lerner UH, Ohlsson C. The WNT system:background and its role in bone[J]. J Intern Med, 2015, 277:630-649.
[10] Inestrosa NC, Arenas E. Emerging roles of Wnts in the adult nervous system[J]. Nat Rev Neurosci, 2010, 11:77-86.
[11] Shi Y, Yuan S, Li B, et al. Regulation of Wnt signaling by nociceptive input in animal models[J]. Mol Pain, 2012, 8:47.
[12] Shi Y, Shu J, Gelman BB, et al. Wnt signaling in the pathogenesis of human HIV-associated pain syndromes[J]. J Neuroimmun Pharmacol, 2013, 8:956-964.
[13] Zhu A, Shen L, Xu L, et al. Suppression of Wnt5a, but not Wnts, relieves chronic post-thoracotomy pain via anti-inflammatory modulation in rats[J]. Biochem Biophys Res Commun, 2017, 493:474-480.
[14] Gao K, Zhang T, Wang F, et al. Therapeutic potential of Wnt-3a in neurological recovery after spinal cord injury[J]. Eur Neurol, 2019, 81:197-204.
[15] van Amerongen R, Nusse R. Towards an integrated view of Wnt signaling in development[J]. Development, 2009, 136:3205-3214.
[16] Jenny A. Planar cell polarity signaling in the drosophila eye[J]. Curr Top Dev Biol, 2010, 93:189-227.
[17] Simonetti M, Agarwal N, Stösser S, et al. Wnt-Fzd signaling sensitizes peripheral sensory neurons via distinct noncanonical pathways[J]. Neuron, 2014, 83:104-121.
[18] Kühl M, Sheldahl LC, Park M, et al. The Wnt/Ca2+ pathway:a new vertebrate Wnt signaling pathway takes shape[J]. Trends Genet, 2000, 16:279-283.
[19] Zhang YK, Huang ZJ, Liu S, et al. WNT signaling underlies the pathogenesis of neuropathic pain in rodents[J]. J Clin Invest, 2013, 123:2268-2286.
[20] Zhao Y, Yang Z. Effect of Wnt signaling pathway on pathogenesis and intervention of neuropathic pain[J]. Exp Ther Med, 2018, 16:3082-3088.
[21] Liu XJ, Gingrich JR, Vargas-Caballero M, et al. Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex[J]. Nat Med, 2008, 14:1325-1332.
[22] Liu S, Liu YP, Huang ZJ, et al. Wnt/Ryk signaling contributes to neuropathic pain by regulating sensory neuron excitability and spinal synaptic plasticity in rats[J]. Pain, 2015, 156:2572-2584.
[23] Yang QO, Yang WJ, Li J, et al. Ryk receptors on unmyelinated nerve fibers mediate excitatory synaptic transmission and CCL2 release during neuropathic pain induced by peripheral nerve injury[J]. Mol Pain, 2017, 13:1744806917709372.
[24] Schmitt AM, Shi J, Wolf AM, et al. Wnt-Ryk signalling mediates medial-lateral retinotectal topographic mapping[J]. Nature, 2006, 439:31-37.
[25] Song XJ, Wang ZB, Gan Q, et al. cAMP and cGMP contribute to sensory neuron hyperexcitability and hyperalgesia in rats with dorsal root ganglia compression[J]. J Neurophysiol, 2006, 95:479-492.
[26] Liu WT, Han Y, Li HC, et al. An in vivo mouse model of long-term potentiation at synapses between primary afferent C-fibers and spinal dorsal horn neurons:essential role of EphB1 receptor[J]. Mol Pain, 2009, 5:29.
[27] Tang J, Ji Q, Jin L, et al. Secreted frizzled-related protein 1 regulates the progression of neuropathic pain in mice following spinal nerve ligation[J]. J Cell Physiol, 2018, 233:5815-5822.
[28] Itokazu T, Hayano Y, Takahashi R, et al. Involvement of Wnt/β-catenin signaling in the development of neuropathic pain[J]. Neurosci Res, 2014, 79:34-40.
[29] Tsuda M, Inoue K, Salter MW. Neuropathic pain and spinal microglia:a big problem from molecules in "small" glia[J]. Trends Neurosci, 2005, 28:101-107.
[30] Scholz J, Woolf CJ. The neuropathic pain triad:neurons, immune cells and glia[J]. Nat Neurosci, 2007, 10:1361-1368.
[31] Siniscalco D, Giordano C, Rossi F, et al. Role of neurotrophins in neuropathic pain[J]. Curr Neuropharmacol, 2011, 9:523-529.
[32] Trang T, Beggs S, Salter MW. Brain-derived neurotrophic factor from microglia:a molecular substrate for neuropathic pain[J]. Neuron Glia Biol, 2011, 7:99-108.
[33] Aouizerat BE, Miaskowski CA, Gay C, et al. Risk factors and symptoms associated with pain in HIV-infected adults[J]. J Assoc Nurses AIDS Care, 2010, 21:125-133.
[34] Li Y, Li B, Wan X, et al. NMDA receptor activation stimulates transcription-independent rapid Wnt5a protein synthesis via the MAPK signaling pathway[J]. Mol Brain, 2012, 5:1.
[35] Farías GG, Alfaro IE, Cerpa W, et al. Wnt-5a/JNK signaling promotes the clustering of PSD-95 in hippocampal neurons[J]. J Biol Chem, 2009, 284:15857-15866.
[36] Varela-Nallar L, Alfaro IE, Serrano FG, et al. Wingless-type family member 5A (Wnt-5a) stimulates synaptic differentiation and function of glutamatergic synapses[J]. Proc Natl Acad Sci U S A, 2010, 107:21164-21169.
[37] Li B, Shi Y, Shu J, et al. Wingless-type mammary tumor virus integration site family, member 5A (Wnt5a) regulates human immunodeficiency virus type 1(HIV-1) envelope glycoprotein 120(gp120)-induced expression of pro-inflammatory cytokines via the Ca2+/calmodulin-dependent protein kinase II (CaMKII) and c-Jun N-terminal kinase (JNK) signaling pathways[J]. J Biol Chem, 2013, 288:13610-13619.
[38] van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, et al. Prevalence of pain in patients with cancer:a systematic review of the past 40 years[J]. Ann Oncol, 2007, 18:1437-1449.
[39] Kawano Y, Kypta R. Secreted antagonists of the Wnt signalling pathway[J]. J Cell Sci, 2003, 116:2627-2634.
[40] Ganesan K, Xu B. Anti-diabetic effects and mechanisms of dietary polysaccharides[J]. Molecules, 2019. DOI:10.3390/molecules24142556.
[41] Banafshe HR, Hamidi GA, Noureddini M, et al. Effect of curcumin on diabetic peripheral neuropathic pain:possible involvement of opioid system[J]. Eur J Pharmacol, 2014, 723:202-206.
[42] Abbott CA, Malik RA, van Ross ER, et al. Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the UK[J]. Diabetes Care, 2011, 34:2220-2224.
[43] Michalski D, Liebig S, Thomae E, et al. Pain in patients with multiple sclerosis:a complex assessment including quantitative and qualitative measurements provides for a disease-related biopsychosocial pain model[J]. J Pain Res, 2011, 4:219-225.
[44] Yuan S, Shi Y, Tang SJ. Wnt signaling in the pathogenesis of multiple sclerosis-associated chronic pain[J]. J Neuroimmune Pharmacol, 2012, 7:904-913.
[45] Kiguchi N, Kobayashi Y, Kishioka S. Chemokines and cytokines in neuroinflammation leading to neuropathic pain[J]. Curr Opin Pharmacol, 2012, 12:55-61.
[46] Wang VC, Mullally WJ. Pain neurology[J]. Am J Med, 2019. DOI:10.1016/j.amjmed.2019.07.029.
[47] Dai D, Wang J, Jiang Y, et al. Small RNA sequencing reveals microRNAs related to neuropathic pain in rats[J]. Braz J Med Biol Res, 2019, 52:e8380.