Exploring the possibilities of using in vitro model for neuropathic pain studies


  • Noor Aishah Mohammed Izham (1) Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia. (2) Department of Diagnostic Health and Allied Science, Faculty of Health and Life Sciences, Management and Science University, Selangor, Malaysia.
  • Jasmine Siew Min Chia School of Pharmacy, Management and Science University, Selangor, Malaysia.
  • Nur Khalisah Kaswan Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia.
  • Kavitha Sukirthalingam Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia.
  • Sharmili Vidyadaran Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia.
  • Hemabarathy Bharatham Department of Biomedical Science, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Selangor, Malaysia.
  • Mohd Roslan Sulaiman Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia.
  • Enoch Kumar Perimal (1) Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia. (2) Centre of Excellence for Nanoscale BioPhotonics, Australian Research Council, University of Adelaide, Adelaide, Australia.




neuropathic pain, in vitro, receptors, inflammatory mediators


Establishing experimental models to study neuropathic pain has been challenging due to the complex mechanism underlying the condition. Although in vivo models have been useful in the observation of behavioural pain responses, it should be acknowledged that species-to-species variance can lead to differences in terms of molecular mechanism and genetic expression. The study of molecular and signal transduction of neuropathic pain using in vivo models faces limitations due to ethical considerations involving pain induction in animals and the intricacy of molecular interactions in the pathophysiology of the condition. Hence, developing relevant in vitro models to study neuropathic pain is important, as it considers the physiological microenvironment and reduces the use of experimental animals. Several considerations should be taken into account in developing an in vitro model of neuropathic pain, including the use of either primary culture of cell lines with considerations to their origins; human or animal, the method of neuropathic pain-like induction and the relevant assays to assess pain. This review recapitulates previous research employing in vitro models in investigating the molecular mechanism of neuropathic pain, intending to provide an alternative to the growing concerns on in vivo neuropathic pain models.


Addis, D. R., DeBerry, J. J., & Aggarwal, S. (2020). Chronic pain in HIV. Molecular Pain, 16, 1744806920927276. https://doi.org/10.1177/1744806920927276

Afrazi, S., Esmaeili-mahani, S., Sheibani, V., & Abbasnejad, M. (2014). Neurosteroid allopregnanolone attenuates high glucose-induced apoptosis and prevents experimental diabetic neuropathic pain : In vitro and in vivo studies. Journal of Steroid Biochemistry and Molecular Biology, 139, 98–103. https://doi.org/10.1016/j.jsbmb.2013.10.010

Alles, S. R. A., & Smith, P. A. (2018). Etiology and pharmacology of neuropathic pain. Pharmacol Rev, 70, 315–347. https://doi.org/10.1124/pr.117.014399

Amine, H., Benomar, Y., & Taouis, M. (2021). Palmitic acid promotes resistin-induced insulin resistance and inflammation in SH-SY5Y human neuroblastoma. Scientific Reports, 11(1), 5427. https://doi.org/10.1038/s41598-021-85018-7

Anand, U., Yiangou, Y., Sinisi, M., Fox, M., MacQuillan, A., Quick, T., … Anand, P. (2015). Mechanisms underlying clinical efficacy of Angiotensin II type 2 receptor (AT2R) antagonist EMA401 in neuropathic pain: clinical tissue and in vitro studies. Molecular Pain, 11, 38. https://doi.org/10.1186/s12990-015-0038-x

Anderson, W. A., Willenberg, A. R., Bosak, A. J., Willenberg, B. J., & Lambert, S. (2018). Use of a capillary alginate gel (CapgelTM) to study the three-dimensional development of sensory nerves reveals the formation of a rudimentary perineurium. Journal of Neuroscience Methods, 305, 46–53. https://doi.org/10.1016/j.jneumeth.2018.05.003

Barkai, O., Goldstein, R. H., Caspi, Y., Katz, B., Lev, S., & Binshtok, A. M. (2017). The role of kv7/m potassium channels in controlling ectopic firing in nociceptors. Frontiers in Molecular Neuroscience, 10, 181. https://doi.org/10.3389/fnmol.2017.00181

Berta, T., Qadri, Y., Tan, P.-H., & Ji, R.-R. (2017). Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain. Expert Opinion on Therapeutic Targets, 21(7), 695–703. https://doi.org/10.1080/14728222.2017.1328057

Carrasco, C., Naziroǧlu, M., Rodríguez, A. B., & Pariente, J. A. (2018). Neuropathic pain: delving into the oxidative origin and the possible implication of transient receptor potential channels. Frontiers in Physiology, 9, 95. https://doi.org/10.3389/fphys.2018.00095

Carter, M., Shieh, J., Carter, M., & Shieh, J. (2015). Cell Culture Techniques. Guide to Research Techniques in Neuroscience, 295–310. https://doi.org/10.1016/B978-0-12-800511-8.00014-9

Challa, S. R. (2015). Surgical animal models of neuropathic pain: Pros and Cons. International Journal of Neuroscience, 125(3), 170–174. https://doi.org/10.3109/00207454.2014.922559

Chambers, S. M., Mica, Y., Lee, G., Studer, L., & Tomishima, M. J. (2013). Dual-SMAD inhibition/WNT activation-based methods to induce neural crest and derivatives from human pluripotent stem cells (pp. 329–343). Humana Press, New York, NY. https://doi.org/10.1007/7651_2013_59

Chanchal, S. K., Mahajan, U. B., Siddharth, S., Reddy, N., Goyal, S. N., Patil, P. H., … Ojha, S. (2016). In vivo and in vitro protective effects of omeprazole against neuropathic pain. Scientific Reports, 6(1), 30007. https://doi.org/10.1038/srep30007

Chen, C., Dong, X., Fang, K.-H., Yuan, F., Hu, Y., Xu, M., … Liu, Y. (2019). Develop a 3D neurological disease model of human cortical glutamatergic neurons using micropillar-based scaffolds. Acta Pharmaceutica Sinica B, 9(3), 557–564. https://doi.org/10.1016/J.APSB.2019.03.004

Chen, T., Li, H., Yin, Y., Zhang, Y., Liu, Z., & Liu, H. (2017). Interactions of Notch1 and TLR4 signaling pathways in DRG neurons of in vivo and in vitro models of diabetic neuropathy. Scientific Reports, 7(1), 14923.


Chia, J. S. M., Izham, N. A. M., Farouk, A. A. O., Sulaiman, M. R., Mustafa, S., Hutchinson, M. R., & Perimal, E. K. (2020). Zerumbone modulates α2A-adrenergic, TRPV1, and NMDA NR2B receptors plasticity in CCI-induced neuropathic pain in vivo and LPS-induced SH-SY5Y neuroblastoma in vitro models. Frontiers in Pharmacology, 11, 92. https://doi.org/10.3389/fphar.2020.00092

Chung, J. M., & Chung, K. (2002). Importance of hyperexcitability of DRG neurons in neuropathic pain. Pain Practice, 2(2), 87–97. https://doi.org/10.1046/j.1533-2500.2002.02011.x

Cohen, S. P., & Mao, J. (2014). Neuropathic pain: mechanisms and their clinical implications. BMJ, 348, f7656–f7656. https://doi.org/10.1136/bmj.f765

Colloca, L., Ludman, T., Bouhassira, D., Baron, R., Dickenson, A. H., Yarnitsky, D., … Raja, S. N. (2017). Neuropathic pain. Nature Reviews. Disease Primers, 3, 17002. https://doi.org/10.1038/nrdp.2017.2

Cotto, B., Natarajanseenivasan, K., & Langford, D. (2019). HIV-1 infection alters energy metabolism in the brain: Contributions to HIV-associated neurocognitive disorders. Progress in Neurobiology, 181, 101616. https://doi.org/10.1016/j.pneurobio.2019.101616

Damasceno, D. C., Netto, A. O., Iessi, I. L., Gallego, F. Q., Corvino, S. B., Dallaqua, B., … Rudge, M. V. C. (2014). Streptozotocin-induced diabetes models: Pathophysiological mechanisms and fetal outcomes. BioMed Research International, 2014, 819065. https://doi.org/10.1155/2014/819065

Datta, G., Miller, N. M., Afghah, Z., Geiger, J. D., & Chen, X. (2019). HIV-1 gp120 Promotes lysosomal exocytosis in human schwann cells. Frontiers in Cellular Neuroscience, 13, 329. https://doi.org/10.3389/fncel.2019.00329

Dave, K. M., Ali, L., & Manickam, D. S. (2020). Characterisation of the SIM-A9 cell line as a model of activated microglia in the context of neuropathic pain. PLOS ONE, 15(4), e0231597. https://doi.org/10.1371/journal.pone.0231597

Dureja, G. P., Narayana Iyer, R., Das, G., Ahdal, J., & Narang, P. (2017). Evidence and consensus recommendations for the pharmacological management of pain in India. Journal of Pain Research, 10, 709–736. https://doi.org/10.2147/JPR.S128655

Eldridge, S., Guo, L., & Hamre, J. (2019). A comparative review of chemotherapy-induced peripheral neuropathy in in vivo and in vitro models. Toxicologic Pathology, 48(1), 190–201. https://doi.org/10.1177/0192623319861937

Elmann, A., Telerman, A., Ofir, R., & Kashman, Y. (2017). Glutamate toxicity to differentiated neuroblastoma n2a cells is prevented by the sesquiterpene lactone achillolide a and the flavonoid 3,5,4′-trihydroxy-6,7,3′-trimethoxyflavone from Achillea fragrantissima. Journal of Molecular Neuroscience, 62(1), 99–105. https://doi.org/10.1007/s12031-017-0916-y

Encinas, M., Iglesias, M., Liu, Y., Wang, H., Muhaisen, A., Ceña, V., … Comella, J. X. (2000). Sequential treatment of SH-SY5Y cells with retinoic acid and brain-derived neurotrophic factor gives rise to fully differentiated, neurotrophic factor-dependent, human neuron-like cells. Journal of Neurochemistry, 75(3), 991–1003.


Fernyhough, P., Huang, T.-J., & Verkhratsky, A. (2003). Mechanism of mitochondrial dysfunction in diabetic sensory neuropathy. Journal of the Peripheral Nervous System, 8(4), 227–235.


Finnerup, N. B., Kuner, R., & Jensen, T. S. (2021). Neuropathic pain: from mechanisms to treatment. Physiological Reviews, 101(1):259-301. https://doi.org/10.1152/physrev.00045.2019

Forrest, C. M., Darlington, L. G., Smith, R. A., & Stone, T. W. (2017). Quinolinic acid induces neuritogenesis in SH-SY5Y neuroblastoma cells independently of NMDA receptor activation, 45, 700–711. https://doi.org/10.1111/ejn.13499

Gardiner, N. J., & Freeman, O. J. (2016). Can diabetic neuropathy be modeled in vitro? International Review of Neurobiology, 127:53-87. https://doi.org/10.1016/bs.irn.2016.02.004

Geraghty, R. J., Capes-Davis, A., Davis, J. M., Downward, J., Freshney, R. I., Knezevic, I., … Cancer Research UK. (2014). Guidelines for the use of cell lines in biomedical research. British Journal of Cancer, 111(6), 1021–1046. https://doi.org/10.1038/bjc.2014.166

Gordon, J., Amini, S., & White, M. K. (2013). Neuronal cell culture, 1078, 1–6. https://doi.org/10.1007/978-1-62703-640-5

Greaves, M., & Maley, C. C. (2012). Clonal evolution in cancer. Nature, 481(7381), 306–313. https://doi.org/10.1038/nature10762

Gregory, N. S., Harris, A. L., Robinson, C. R., Dougherty, P. M., Fuchs, P. N., & Sluka, K. A. (2013). An overview of animal models of pain: Disease models and outcome measures. Journal of Pain, 14(11), 1255–1269. https://doi.org/10.1016/j.jpain.2013.06.008

Gwak, Y. S., & Hulsebosch, C. E. (2011). Neuronal hyperexcitability: A substrate for central neuropathic pain after spinal cord injury. Current Pain and Headache Reports, 15(3), 215–222. https://doi.org/10.1007/s11916-011-0186-2

Hattangady, N., & Rajadhyaksha, M. (2009). A brief review of in vitro models of diabetic neuropathy. International Journal of Diabetes in Developing Countries, 29(4), 143. https://doi.org/10.4103/0973-3930.57344

IASP Terminology - IASP. (2017). Retrieved December 23, 2019, from https://www.iasp-pain.org/Education/Content.aspx?ItemNumber=1698#Hyperalgesia

Imai, S., Koyanagi, M., Azimi, Z., Nakazato, Y., Matsumoto, M., Ogihara, T., … Matsubara, K. (2017). Taxanes and platinum derivatives impair Schwann cells via distinct mechanisms. Scientific Reports, 7(1), 5947. https://doi.org/10.1038/s41598-017-05784-1

Maqsood M.I., Matin M.M., Bahrami A.R., Ghasroldasht M.M. (2013). Immortality of cell lines: challenges and advantages of establishment. Cell Biology International, 37(10), 1038–1045. https://doi.org/10.1002/cbin.10137

Izzi, F., Loser, D., & Cesare, P. (2018). Micro electrode arrays to investigate neuron-glia crosstalk in neuropathic pain in-vitro models. Frontiers in Cellular Neuroscience, 12. https://doi.org/10.3389/conf.fncel.2018.38.00029

Jaggi, A. S., Jain, V., & Singh, N. (2011). Animal models of neuropathic pain. Fundamental and Clinical Pharmacology, 25(1), 1–28. https://doi.org/10.1111/j.1472-8206.2009.00801.x

Jay, G. W., & Barkin, R. L. (2014). Neuropathic pain: Etiology, pathophysiology, mechanisms, and evaluations. Disease-a-Month, 60(1), 6–47. https://doi.org/10.1016/j.disamonth.2013.12.001

Jones, I., Yelhekar, T. D., Wiberg, R., Kingham, P. J., Johansson, S., Wiberg, M., & Carlsson, L. (2018a). Development and validation of an in vitro model system to study peripheral sensory neuron development and injury. Scientific Reports, 8(1), 15961. https://doi.org/10.1038/s41598-018-34280-3

Kaeidi, A., Esmaeili-Mahani, S., Sheibani, V., Abbasnejad, M., Rasoulian, B., Hajializadeh, Z., & Afrazi, S. (2011). Olive (Olea europaea L.) leaf extract attenuates early diabetic neuropathic pain through prevention of high glucose-induced apoptosis: In vitro and in vivo studies. Journal of Ethnopharmacology, 136(1), 188–196. https://doi.org/10.1016/j.jep.2011.04.038

Kaliyaperumal, S., Wilson, K., Aeffner, F., & Dean, C. (2020). Animal models of peripheral pain: biology review and application for drug discovery. Toxicologic Pathology, 48(1), 202–219. https://doi.org/10.1177/0192623319857051

Kamerman, P. R., Moss, P. J., Weber, J., Wallace, V. C. J., Rice, A. S. C., & Huang, W. (2012). Pathogenesis of HIV-associated sensory neuropathy: evidence from in vivo and in vitro experimental models. Journal of the Peripheral Nervous System, 17(1), 19–31. https://doi.org/10.1111/j.1529-8027.2012.00373.x

Kaswan, N. K., Mohd Suhaimi, N. S., Mohammed Izham, N. A., Tengku Mohamad, T. A. S., Sulaiman, M. R., & Perimal, E. K. (2020). Cardamonin inhibits nitric oxide production modulated through NMDA receptor in LPS-Induced SH-SY5Y cell in vitro model. Life Sciences, Medicine and Biomedicine, 4(9). https://doi.org/10.28916/lsmb.4.9.2020.58

Kaur, G., & Dufour, J. M. (2012). Cell lines: Valuable tools or useless artifacts. Spermatogenesis, 2(1), 1–5. https://doi.org/10.4161/spmg.19885

Kim, H.-S., Kim, J. Y., Song, C. L., Jeong, J. E., & Cho, Y. S. (2020). Directly induced human Schwann cell precursors as a valuable source of Schwann cells. Stem Cell Research & Therapy, 11(1), 257.


Kovalevich, J., & Langford, D. (2013). Considerations for the use of SH-SY5Y neuroblastoma cells in neurobiology. Methods in Molecular Biology (Clifton, N.J.), 1078, 9–21. https://doi.org/10.1007/978-1-62703-640-5_2

Krames, E. S. (2014). The role of the dorsal root ganglion in the development of neuropathic pain. Pain Medicine, 15(10), 1669–1685. https://doi.org/10.1111/pme.12413

Lampert, A., Bennett, D. L., McDermott, L. A., Neureiter, A., Eberhardt, E., Winner, B., & Zenke, M. (2020). Human sensory neurons derived from pluripotent stem cells for disease modelling and personalised medicine. Neurobiology of Pain, 8, 100055. https://doi.org/10.1016/J.YNPAI.2020.100055

Lawrimore, C. J., & Crews, F. T. (2017). Ethanol, TLR3, and TLR4 agonists have unique innate immune responses in neuron-like SH-SY5Y and microglia-like BV2. Alcoholism, Clinical and Experimental Research, 41(5), 939–954. https://doi.org/10.1111/acer.13368

Lee, K. S., Zhou, W., Scott-McKean, J. J., Emmerling, K. L., Cai, G., Krah, D. L., … Levin, M. J. (2012). Human sensory neurons derived from induced pluripotent stem cells support Varicella-Zoster virus infection. PLoS ONE, 7(12), e53010. https://doi.org/10.1371/journal.pone.0053010

Lehmann, H. C., Staff, N. P., & Hoke, A. (2020). Modeling chemotherapy induced peripheral neuropathy (CIPN) in vitro: Prospects and limitations. Experimental Neurology, 326, 113140. https://doi.org/10.1016/J.EXPNEUROL.2019.113140

Liu, D., Liang, X., & Zhang, H. (2016). Effects of high glucose on cell viability and differentiation in primary cultured schwann cells: potential role of ERK signaling pathway. Neurochemical Research, 41(6), 1281–1290. https://doi.org/10.1007/s11064-015-1824-6

Logu, F. De, Puma, S. L., Landini, L., Portelli, F., Innocenti, A., Araujo, D. S. M. de, … Nassini, R. (2019). Schwann cells expressing nociceptive channel TRPA1 orchestrate ethanol-evoked neuropathic pain in mice. The Journal of Clinical Investigation, 129(12), 5424–5441. https://doi.org/10.1172/JCI128022

Lu, M., Yi, T., Xiong, Y., Wang, Q., & Yin, N. (2019). Cortex Mori Radicis extract promotes neurite outgrowth in diabetic rats by activating PI3K/AKT signaling and inhibiting Ca2+ influx associated with the upregulation of transient receptor potential canonical channel 1. Molecular Medicine Reports, 21(1), 320–328. https://doi.org/10.3892/mmr.2019.10839

Melli, G., & Höke, A. (2009). Dorsal Root Ganglia Sensory Neuronal Cultures: a tool for drug discovery for peripheral neuropathies. Expert Opinion on Drug Discovery, 4(10), 1035–1045. https://doi.org/10.1517/17460440903266829

Meyer, K., & Kaspar, B. K. (2014). Making sense of pain: are pluripotent stem cell-derived sensory neurons a new tool for studying pain mechanisms? Molecular Therapy : The Journal of the American Society of Gene Therapy, 22(8), 1403–1405. https://doi.org/10.1038/mt.2014.123

Meacham, K., Shepherd, A., Mohapatra, D. P., & Haroutounian, S. (2017). Neuropathic pain: central vs. peripheral mechanisms. Current Pain and Headache Reports, 21(6):28. https://doi.org/10.1007/s11916-017-0629-5

Melli, G., & Höke, A. (2009). Dorsal Root Ganglia Sensory Neuronal Cultures: a tool for drug discovery for peripheral neuropathies. Expert Opinion on Drug Discovery, 4(10), 1035–1045. https://doi.org/10.1517/17460440903266829

Meyer, K., & Kaspar, B. K. (2014). Making sense of pain: are pluripotent stem cell-derived sensory neurons a new tool for studying pain mechanisms? Molecular Therapy : The Journal of the American Society of Gene Therapy, 22(8), 1403–1405. https://doi.org/10.1038/mt.2014.123

Mogil, J. S. (2009). Animal models of pain: Progress and challenges. Nature Reviews Neuroscience, 10(4), 283–294. https://doi.org/10.1038/nrn2606

Moss, P. J., Huang, W., Dawes, J., Okuse, K., McMahon, S. B., & Rice, A. S. C. (2015). Macrophage-sensory neuronal interaction in HIV-1 gp120-induced neurotoxicity. British Journal of Anaesthesia, 114(3), 499–508. https://doi.org/10.1093/bja/aeu311

Murillo, J. R., Goto-Silva, L., Sánchez, A., Nogueira, F. C. S., Domont, G. B., & Junqueira, M. (2017). Quantitative proteomic analysis identifies proteins and pathways related to neuronal development in differentiated SH-SY5Y neuroblastoma cells. EuPA Open Proteomics, 16, 1–11. https://doi.org/10.1016/J.EUPROT.2017.06.001

Nishikawa, N., & Nomoto, M. (2017). Management of neuropathic pain. Journal of General and Family Medicine, 18(2), 56–60. https://doi.org/10.1002/jgf2.5

Nopparat, C., Chantadul, V., Permpoonputtana, K., & Govitrapong, P. (2017). The anti-inflammatory effect of melatonin in SH-SY5Y neuroblastoma cells exposed to sublethal dose of hydrogen peroxide. Mechanisms of Ageing and Development, 164, 49–60. https://doi.org/10.1016/j.mad.2017.04.001

Pandur, E., Varga, E., Tamási, K., Pap, R., Nagy, J., & Sipos, K. (2018). Effect of inflammatory mediators lipopolysaccharide and lipoteichoic acid on iron metabolism of differentiated SH-SY5Y cells alters in the presence of BV-2 microglia. International Journal of Molecular Sciences, 20(1), 17. https://doi.org/10.3390/ijms20010017

Podratz, J. L., Kulkarni, A., Pleticha, J., Kanwar, R., Beutler, A. S., Staff, N. P., & Windebank, A. J. (2016). Neurotoxicity to DRG neurons varies between rodent strains treated with cisplatin and bortezomib. Journal of the Neurological Sciences, 362, 131–135. https://doi.org/10.1016/j.jns.2015.12.038

Pousinha, P. A., Mouska, X., Raymond, E. F., Gwizdek, C., Dhib, G., Poupon, G., … Marie, H. (2017). Physiological and pathophysiological control of synaptic GluN2B-NMDA receptors by the C-terminal domain of amyloid precursor protein. ELife, 6, e25659. https://doi.org/10.7554/eLife.25659

Prajumwongs, P., Weeranantanapan, O., Jaroonwitchawan, T., & Noisa, P. (2016). Human embryonic stem cells : a model for the study of neural development and neurological diseases. Stem Cells International, 2016, 2958210. https://doi.org/10.1155/2016/2958210

Qi J., Buzas K., Fan H., Cohen J.I., Wang K., Mont E., Klinman D., Oppenheim J.J., & Howard O.M. (2011). Neurons stimulation of dorsal root ganglion painful pathways induced by TLR. Journal of Immunology, 186(11), 6417-6426. https://doi.org/10.4049/jimmunol.1001241

Rohm, B., Holik, A., Somoza, M. M., Pignitter, M., Zaunschirm, M., Krammer, G. E., & Somoza, V. (2018). Nonivamide , a capsaicin analog , increases dopamine and serotonin release in SH-SY5Y cells via a TRPV1-independent pathway. Molecular Nutrition and Food Research, 57, 2008-2018. https://doi.org/10.1002/mnfr.201200846

Sambasevam, Y. (2018). Antihyperalgesic and anti-allodynic properties of cardamonin in mice model of neuropathic pain. Universiti Putra Malaysia. http://psasir.upm.edu.my/id/eprint/76305/1/FPSK%28P%29%202018%2016%20-%20IR.pdf

Sango, K., Yanagisawa, H., Takaku, S., Kawakami, E., & Watabe, K. (2011). Immortalised adult rodent Schwann cells as in vitro models to study diabetic neuropathy. Experimental Diabetes Research, 2011, 374943. https://doi.org/10.1155/2011/374943

Schreiber, A. K., Nones, C. F., Reis, R. C., Chichorro, J. G., & Cunha, J. M. (2015). Diabetic neuropathic pain: Physiopathology and treatment. World Journal of Diabetes, 6(3), 432–444. https://doi.org/10.4239/wjd.v6.i3.432

Schütz, S. G., & Robinson-Papp, J. (2013). HIV-related neuropathy: current perspectives. HIV/AIDS (Auckland, N.Z.), 5, 243–251. https://doi.org/10.2147/HIV.S36674

Shen, H., Gan, M., Yang, H., & Zou, J. (2019). An integrated cell isolation and purification method for rat dorsal root ganglion neurons. The Journal of International Medical Research, 47(7), 3253–3260. https://doi.org/10.1177/0300060519855585

Sousa, A. M., Lages, G. V., Pereira, C. L., Slullitel, A., Sousa, A. M., Lages, G. V., … Slullitel, A. (2016). Experimental models for the study of neuropathic pain. Revista Dor, 17, 27–30. https://doi.org/10.5935/1806-0013.20160043

Srinivasan, A., & Toh, Y.-C. (2019). Human pluripotent stem cell-derived neural crest cells for tissue regeneration and disease modeling. Frontiers in Molecular Neuroscience, 12, 39. https://doi.org/10.3389/fnmol.2019.00039

Stacey, G. (2006). Primary cell cultures and immortal cell Lines. In Encyclopedia of Life Sciences. Chichester, UK: John Wiley & Sons, Ltd. https://doi.org/10.1038/npg.els.0003960

Starobova, H., & Vetter, I. (2017). Pathophysiology of chemotherapy-induced peripheral neuropathy. Frontiers in Molecular Neuroscience, 10, 174. https://doi.org/10.3389/fnmol.2017.00174

Su, W.-F., Wu, F., Jin, Z.-H., Gu, Y., Chen, Y.-T., Fei, Y., … Chen, G. (2019). Overexpression of P2X4 receptor in Schwann cells promotes motor and sensory functional recovery and remyelination via BDNF secretion after nerve injury. Glia, 67(1), 78–90. https://doi.org/10.1002/glia.23527

Sun, P., Ortega, G., Tan, Y., Hua, Q., Riederer, P. F., Deckert, J., & Schmitt-Böhrer, A. G. (2018). Streptozotocin impairs proliferation and differentiation of adult hippocampal neural stem cells in vitro-correlation with alterations in the expression of proteins associated with the insulin system. Frontiers in Aging Neuroscience, 10, 145. https://doi.org/10.3389/fnagi.2018.00145

Teppola, H., Tuula, J. S., & Linne, O. J. M. (2016). Morphological differentiation towards neuronal phenotype of sh-sy5y neuroblastoma cells by estradiol , retinoic acid and cholesterol. Neurochemical Research, 41(4), 731–747. https://doi.org/10.1007/s11064-015-1743-6

Tremblay, R. G., Sikorska, M., Sandhu, J. K., Lanthier, P., Ribecco-Lutkiewicz, M., & Bani-Yaghoub, M. (2010). Differentiation of mouse Neuro 2A cells into dopamine neurons. Journal of Neuroscience Methods, 186(1), 60–67. https://doi.org/10.1016/J.JNEUMETH.2009.11.004

Tsukahara, R., & Ueda, H. (2016). Myelin-related gene silencing mediated by LPA1 – Rho/ROCK signaling is correlated to acetylation of NFκB in S16 Schwann cells. Journal of Pharmacological Sciences, 132(2), 162–165. https://doi.org/10.1016/J.JPHS.2016.07.010

van Hecke, O., Austin, S. K., Khan, R. A., Smith, B. H., & Torrance, N. (2014). Neuropathic pain in the general population: A systematic review of epidemiological studies. Pain, 155(4), 654–662. https://doi.org/10.1016/j.pain.2013.11.013

Vysokov, N., McMahon, S. B., & Raouf, R. (2019). The role of NaV channels in synaptic transmission after axotomy in a microfluidic culture platform. Scientific Reports, 9(1), 12915. https://doi.org/10.1038/s41598-019-49214-w

Wang, L. X., & Wang, Z. J. (2003). Animal and cellular models of chronic pain. Advanced Drug Delivery Reviews, 55(8), 949–965. https://doi.org/10.1016/S0169-409X(03)00098-X

Wei, Z., Fei, Y., Su, W., & Chen, G. (2019). Emerging role of schwann cells in neuropathic pain: receptors, glial mediators and myelination. Frontiers in Cellular Neuroscience, 13, 116. https://doi.org/10.3389/fncel.2019.00116

Xicoy, H., Wieringa, B., & Martens, G. J. M. (2017). The SH-SY5Y cell line in Parkinson’s disease research: a systematic review. Molecular Neurodegeneration, 12(1), 10. https://doi.org/10.1186/s13024-017-0149-0

Yamamoto, S., & Egashira, N. (2021). Drug repositioning for the prevention and treatment of chemotherapy-induced peripheral neuropathy: a mechanism- and screening-based strategy. Frontiers in Pharmacology, 11, 2157. https://doi.org/10.3389/fphar.2020.607780

Yin, K., Baillie, G. J., & Vetter, I. (2016). Neuronal cell lines as model dorsal root ganglion neurons: A transcriptomic comparison. Molecular Pain, 12. https://doi.org/10.1177/1744806916646111

Young, G. T., Gutteridge, A., Fox, H. DE, Wilbrey, A. L., Cao, L., Cho, L. T., … Stevens, E. B. (2014). Characterising human stem cell-derived sensory neurons at the single-cell level reveals their ion channel expression and utility in pain research. Molecular Therapy : The Journal of the American Society of Gene Therapy, 22(8), 1530–1543. https://doi.org/10.1038/mt.2014.86

Yuan, S., Shi, Y., Chen, J., Zhou, X., Ferguson, M. R., Tan, A., … Tang, S.-J. (2014). Gp120 in the pathogenesis of human immunodeficiency virus-associated pain. Ann Neurol, 75(6), 837–850. https://doi.org/10.1002/ana.24139.Gp120

Zajączkowska, R., Kocot-Kępska, M., Leppert, W., Wrzosek, A., Mika, J., & Wordliczek, J. (2019). Mechanisms of chemotherapy-induced peripheral neuropathy. International Journal of Molecular Sciences, 20(6), 1451. https://doi.org/10.3390/ijms20061451

Zhao, H., Alam, A., Chen, Q., Eusman, M. A., Pal, A., Eguchi, S., … Ma, D. (2017). The role of microglia in the pathobiology of neuropathic pain development: what do we know? British Journal of Anaesthesia, 118(4), 504–516. https://doi.org/10.1093/bja/aex006




How to Cite

Mohammed Izham, N. A., Chia, J. S. M., Kaswan, N. K., Sukirthalingam, K., Vidyadaran, S., Bharatham, H., Sulaiman, M. R. and Perimal, E. K. (2022) “Exploring the possibilities of using in vitro model for neuropathic pain studies”, Neuroscience Research Notes, 5(3), p. 144. doi: 10.31117/neuroscirn.v5i3.144.