The F-11 Sensory Neuron Model: A Scalable In Vitro Platform for Neuropathic Pain and Drug Screening
Keywords:
Analgesic screening, Dorsal root ganglion (DRG), F-11 cell line, Neuronal differentiation, Neuropathic pain
Abstract
Neuropathic pain remains a major therapeutic challenge, largely due to the translational disconnect between preclinical animal models and clinical efficacy in humans. This review critically evaluates the differentiated F-11 cell line, a hybridoma of mouse neuroblastoma and rat embryonic dorsal root ganglion (DRG) neurons, as a scalable, reproducible, and physiologically relevant in vitro platform for neuropathic pain research and analgesic drug screening. A detailed analysis of differentiation strategies highlights the critical interplay of neurotrophic factors (notably NGF), intracellular signaling modulators (such as cAMP elevators), and extracellular matrix cues in driving neuronal maturation. Functional validation via calcium imaging and electrophysiology confirms capsaicin responsiveness and action potential generation, mirroring native nociceptors. Its compatibility with medium-to-high-throughput screening and mechanistic studies including investigation of silent nociceptor sensitization in chronic pain conditions along with emerging applications in neuropathy models, makes it a valuable tool for de-risking drug candidates before animal studies.
Downloads
Download data is not yet available.
References
Amaya-Rodriguez, C. A., Carvajal-Zamorano, K., Bustos, D., Alegría-Arcos, M., & Castillo, K. (2024). A journey from molecule to physiology and in silico tools for drug discovery targeting the transient receptor potential vanilloid type 1 (TRPV1) channel. Frontiers in Pharmacology, 14, 1251061. https://doi.org/10.3389/fphar.2023.1251061
Baldassarro, V. A., Cescatti, M., Rocco, M. L., Aloe, L., Lorenzini, L., Giardino, L., & Calzà, L. (2023). Nerve growth factor promotes differentiation and protects the oligodendrocyte precursor cells from in vitro hypoxia/ischemia. Frontiers in Neuroscience, 17, 1111170. https://doi.org/10.3389/fnins.2023.1111170
Barabas, M. E., Kossyreva, E. A., & Stucky, C. L. (2012). TRPA1 Is Functionally Expressed Primarily by IB4-Binding, Non-Peptidergic Mouse and Rat Sensory Neurons. PLoS ONE, 7(10), e47988. https://doi.org/10.1371/journal.pone.0047988
Bertin, S., Aoki-Nonaka, Y., de Jong, P. R., Nohara, L. L., Xu, H., Stanwood, S. R., Srikanth, S., Lee, J., To, K., Abramson, L., Yu, T., Han, T., Touma, R., Li, X., González-Navajas, J. M., Herdman, S., Corr, M., Fu, G., Dong, H., … Raz, E. (2014). The ion channel TRPV1 regulates the activation and proinflammatory properties of CD4+ T cells. Nature Immunology, 15(11), 1055–1063. https://doi.org/10.1038/ni.3009
Cao, B., Xu, Q., Shi, Y., Zhao, R., Li, H., Zheng, J., Liu, F., Wan, Y., & Wei, B. (2024). Pathology of pain and its implications for therapeutic interventions. Signal Transduction and Targeted Therapy, 9(1), 155. https://doi.org/10.1038/s41392-024-01845-w
Chrysostomidou, L., Cooper, A. H., & Weir, G. A. (2021). Cellular models of pain: New technologies and their potential to progress preclinical research. Neurobiology of Pain (Cambridge, Mass.), 10, 100063. https://doi.org/10.1016/j.ynpai.2021.100063
Doan, L. V., Eydlin, O., Piskoun, B., Kline, R. P., Recio-Pinto, E., Rosenberg, A. D., Blanck, T. J. J., & Xu, F. (2014). Despite differences in cytosolic calcium regulation, lidocaine toxicity is similar in adult and neonatal rat dorsal root ganglia in vitro. Anesthesiology, 120(1), 50–61. https://doi.org/10.1097/ALN.0b013e3182a2a561
Ebert, A. D., Liang, P., & Wu, J. C. (2012). Induced pluripotent stem cells as a disease modeling and drug screening platform. Journal of Cardiovascular Pharmacology, 60(4), 408–416. https://doi.org/10.1097/FJC.0b013e318247f642
Erickson, J. T., Brosenitsch, T. A., & Katz, D. M. (2001). Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor are required simultaneously for survival of dopaminergic primary sensory neurons in vivo. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 21(2), 581–589. https://doi.org/10.1523/JNEUROSCI.21-02-00581.2001
Ferrini, F., Salio, C., Boggio, E. M., & Merighi, A. (2021). Interplay of BDNF and GDNF in the Mature Spinal Somatosensory System and Its Potential Therapeutic Relevance. Current Neuropharmacology, 19(8), 1225–1245. https://doi.org/10.2174/1570159X18666201116143422
Haberberger, R. V., Barry, C., & Matusica, D. (2020). Immortalized Dorsal Root Ganglion Neuron Cell Lines. Frontiers in Cellular Neuroscience, 14, 184. https://doi.org/10.3389/fncel.2020.00184
Huang, R., Gao, F., Yu, L., Chen, H., & Zhu, R. (2025). Generation of Neural Organoids and Their Application in Disease Modeling and Regenerative Medicine. Advanced Science, 12(29), e01198. https://doi.org/10.1002/advs.202501198
Hutchings, C. J., Colussi, P., & Clark, T. G. (2019). Ion channels as therapeutic antibody targets. mAbs, 11(2), 265–296. https://doi.org/10.1080/19420862.2018.1548232
Jang, K., & Garraway, S. M. (2024). A review of dorsal root ganglia and primary sensory neuron plasticity mediating inflammatory and chronic neuropathic pain. Neurobiology of Pain (Cambridge, Mass.), 15, 100151. https://doi.org/10.1016/j.ynpai.2024.100151
Kankowski, S., Grothe, C., & Haastert‐Talini, K. (2021). Neuropathic pain: Spotlighting anatomy, experimental models, mechanisms, and therapeutic aspects. European Journal of Neuroscience, 54(2), 4475–4496. https://doi.org/10.1111/ejn.15266
Karcz, M., Abd-Elsayed, A., Chakravarthy, K., Aman, M. M., Strand, N., Malinowski, M. N., Latif, U., Dickerson, D., Suvar, T., Lubenow, T., Peskin, E., D’Souza, R., Cornidez, E., Dudas, A., Lam, C., Farrell Ii, M., Sim, G. Y., Sebai, M., Garcia, R., … Deer, T. (2024). Pathophysiology of Pain and Mechanisms of Neuromodulation: A Narrative Review (A Neuron Project). Journal of Pain Research, 17, 3757–3790. https://doi.org/10.2147/JPR.S475351
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
Khosrowshahi, D., Lagae, L., & Bolander, J. (2025). Decoding Pain: Next‐Generation In Vitro Systems for Mechanistic Insights and Drug Discovery. The FASEB Journal, 39(16), e70914. https://doi.org/10.1096/fj.202501025RR
Lawson, S. N., Fang, X., & Djouhri, L. (2019). Nociceptor subtypes and their incidence in rat lumbar dorsal root ganglia (DRGs): Focussing on C-polymodal nociceptors, Aβ-nociceptors, moderate pressure receptors and their receptive field depths. Current Opinion in Physiology, 11, 125–146. https://doi.org/10.1016/j.cophys.2019.10.005
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
Morwood, A. J., El-Karim, I. A., Clarke, S. A., & Lundy, F. T. (2023). The Role of Extracellular Matrix (ECM) Adhesion Motifs in Functionalised Hydrogels. Molecules (Basel, Switzerland), 28(12), 4616. https://doi.org/10.3390/molecules28124616
Mouraux, A., Bannister, K., Becker, S., Finn, D. P., Pickering, G., Pogatzki-Zahn, E., & Graven-Nielsen, T. (2021). Challenges and opportunities in translational pain research—An opinion paper of the working group on translational pain research of the European pain federation (EFIC). European Journal of Pain (London, England), 25(4), 731–756. https://doi.org/10.1002/ejp.1730
Nair, D. G., & Weiskirchen, R. (2024). Advanced In Vitro Models for Preclinical Drug Safety: Recent Progress and Prospects. Current Issues in Molecular Biology, 47(1), 7. https://doi.org/10.3390/cimb47010007
Orozco Morato, E., Knight, B., & Nair, L. S. (2022). Transcriptional profiling of neuronal ion channels in dorsal root ganglion–derived immortal cell line (F-11) under different culture conditions. In Vitro Models, 1(4–5), 385–395. https://doi.org/10.1007/s44164-022-00036-7
Pastori, V., D’Aloia, A., Blasa, S., & Lecchi, M. (2019). Serum-deprived differentiated neuroblastoma F-11 cells express functional dorsal root ganglion neuron properties. PeerJ, 7, e7951. https://doi.org/10.7717/peerj.7951
Perera, T. H., Lu, X., & Smith Callahan, L. A. (2020). Effect of Laminin Derived Peptides IKVAV and LRE Tethered to Hyaluronic Acid on hiPSC Derived Neural Stem Cell Morphology, Attachment and Neurite Extension. Journal of Functional Biomaterials, 11(1), 15. https://doi.org/10.3390/jfb11010015
Rende, M., Brizi, E., Conner, J., Treves, S., Censier, K., Provenzano, C., Taglialatela, G., Sanna, P. P., & Donato, R. (2000). Nerve growth factor (NGF) influences differentiation and proliferation of myogenic cells in vitro via TrKA. International Journal of Developmental Neuroscience: The Official Journal of the International Society for Developmental Neuroscience, 18(8), 869–885. https://doi.org/10.1016/s0736-5748(00)00041-1
Rosenberger, D. C., Blechschmidt, V., Timmerman, H., Wolff, A., & Treede, R.-D. (2020). Challenges of neuropathic pain: Focus on diabetic neuropathy. Journal of Neural Transmission, 127(4), 589–624. https://doi.org/10.1007/s00702-020-02145-7
Saeed, A. W., & Ribeiro-da-Silva, A. (2012). Non-peptidergic primary afferents are presynaptic to neurokinin-1 receptor immunoreactive lamina I projection neurons in rat spinal cord. Molecular Pain, 8, 64. https://doi.org/10.1186/1744-8069-8-64
Sharma, S., Hansen, J. T., & Notter, M. F. (1990). Effects of NGF and dibutyryl cAMP on neuronal differentiation of embryonal carcinoma cells. International Journal of Developmental Neuroscience: The Official Journal of the International Society for Developmental Neuroscience, 8(1), 33–45. https://doi.org/10.1016/0736-5748(90)90021-s
Sutton, K. G., Martin, D. J., Pinnock, R. D., Lee, K., & Scott, R. H. (2002). Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. British Journal of Pharmacology, 135(1), 257–265. https://doi.org/10.1038/sj.bjp.0704439
Yan, K., Gao, L.-N., Cui, Y.-L., Zhang, Y., & Zhou, X. (2016). The cyclic AMP signaling pathway: Exploring targets for successful drug discovery (Review). Molecular Medicine Reports, 13(5), 3715–3723. https://doi.org/10.3892/mmr.2016.5005
Baldassarro, V. A., Cescatti, M., Rocco, M. L., Aloe, L., Lorenzini, L., Giardino, L., & Calzà, L. (2023). Nerve growth factor promotes differentiation and protects the oligodendrocyte precursor cells from in vitro hypoxia/ischemia. Frontiers in Neuroscience, 17, 1111170. https://doi.org/10.3389/fnins.2023.1111170
Barabas, M. E., Kossyreva, E. A., & Stucky, C. L. (2012). TRPA1 Is Functionally Expressed Primarily by IB4-Binding, Non-Peptidergic Mouse and Rat Sensory Neurons. PLoS ONE, 7(10), e47988. https://doi.org/10.1371/journal.pone.0047988
Bertin, S., Aoki-Nonaka, Y., de Jong, P. R., Nohara, L. L., Xu, H., Stanwood, S. R., Srikanth, S., Lee, J., To, K., Abramson, L., Yu, T., Han, T., Touma, R., Li, X., González-Navajas, J. M., Herdman, S., Corr, M., Fu, G., Dong, H., … Raz, E. (2014). The ion channel TRPV1 regulates the activation and proinflammatory properties of CD4+ T cells. Nature Immunology, 15(11), 1055–1063. https://doi.org/10.1038/ni.3009
Cao, B., Xu, Q., Shi, Y., Zhao, R., Li, H., Zheng, J., Liu, F., Wan, Y., & Wei, B. (2024). Pathology of pain and its implications for therapeutic interventions. Signal Transduction and Targeted Therapy, 9(1), 155. https://doi.org/10.1038/s41392-024-01845-w
Chrysostomidou, L., Cooper, A. H., & Weir, G. A. (2021). Cellular models of pain: New technologies and their potential to progress preclinical research. Neurobiology of Pain (Cambridge, Mass.), 10, 100063. https://doi.org/10.1016/j.ynpai.2021.100063
Doan, L. V., Eydlin, O., Piskoun, B., Kline, R. P., Recio-Pinto, E., Rosenberg, A. D., Blanck, T. J. J., & Xu, F. (2014). Despite differences in cytosolic calcium regulation, lidocaine toxicity is similar in adult and neonatal rat dorsal root ganglia in vitro. Anesthesiology, 120(1), 50–61. https://doi.org/10.1097/ALN.0b013e3182a2a561
Ebert, A. D., Liang, P., & Wu, J. C. (2012). Induced pluripotent stem cells as a disease modeling and drug screening platform. Journal of Cardiovascular Pharmacology, 60(4), 408–416. https://doi.org/10.1097/FJC.0b013e318247f642
Erickson, J. T., Brosenitsch, T. A., & Katz, D. M. (2001). Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor are required simultaneously for survival of dopaminergic primary sensory neurons in vivo. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 21(2), 581–589. https://doi.org/10.1523/JNEUROSCI.21-02-00581.2001
Ferrini, F., Salio, C., Boggio, E. M., & Merighi, A. (2021). Interplay of BDNF and GDNF in the Mature Spinal Somatosensory System and Its Potential Therapeutic Relevance. Current Neuropharmacology, 19(8), 1225–1245. https://doi.org/10.2174/1570159X18666201116143422
Haberberger, R. V., Barry, C., & Matusica, D. (2020). Immortalized Dorsal Root Ganglion Neuron Cell Lines. Frontiers in Cellular Neuroscience, 14, 184. https://doi.org/10.3389/fncel.2020.00184
Huang, R., Gao, F., Yu, L., Chen, H., & Zhu, R. (2025). Generation of Neural Organoids and Their Application in Disease Modeling and Regenerative Medicine. Advanced Science, 12(29), e01198. https://doi.org/10.1002/advs.202501198
Hutchings, C. J., Colussi, P., & Clark, T. G. (2019). Ion channels as therapeutic antibody targets. mAbs, 11(2), 265–296. https://doi.org/10.1080/19420862.2018.1548232
Jang, K., & Garraway, S. M. (2024). A review of dorsal root ganglia and primary sensory neuron plasticity mediating inflammatory and chronic neuropathic pain. Neurobiology of Pain (Cambridge, Mass.), 15, 100151. https://doi.org/10.1016/j.ynpai.2024.100151
Kankowski, S., Grothe, C., & Haastert‐Talini, K. (2021). Neuropathic pain: Spotlighting anatomy, experimental models, mechanisms, and therapeutic aspects. European Journal of Neuroscience, 54(2), 4475–4496. https://doi.org/10.1111/ejn.15266
Karcz, M., Abd-Elsayed, A., Chakravarthy, K., Aman, M. M., Strand, N., Malinowski, M. N., Latif, U., Dickerson, D., Suvar, T., Lubenow, T., Peskin, E., D’Souza, R., Cornidez, E., Dudas, A., Lam, C., Farrell Ii, M., Sim, G. Y., Sebai, M., Garcia, R., … Deer, T. (2024). Pathophysiology of Pain and Mechanisms of Neuromodulation: A Narrative Review (A Neuron Project). Journal of Pain Research, 17, 3757–3790. https://doi.org/10.2147/JPR.S475351
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
Khosrowshahi, D., Lagae, L., & Bolander, J. (2025). Decoding Pain: Next‐Generation In Vitro Systems for Mechanistic Insights and Drug Discovery. The FASEB Journal, 39(16), e70914. https://doi.org/10.1096/fj.202501025RR
Lawson, S. N., Fang, X., & Djouhri, L. (2019). Nociceptor subtypes and their incidence in rat lumbar dorsal root ganglia (DRGs): Focussing on C-polymodal nociceptors, Aβ-nociceptors, moderate pressure receptors and their receptive field depths. Current Opinion in Physiology, 11, 125–146. https://doi.org/10.1016/j.cophys.2019.10.005
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
Morwood, A. J., El-Karim, I. A., Clarke, S. A., & Lundy, F. T. (2023). The Role of Extracellular Matrix (ECM) Adhesion Motifs in Functionalised Hydrogels. Molecules (Basel, Switzerland), 28(12), 4616. https://doi.org/10.3390/molecules28124616
Mouraux, A., Bannister, K., Becker, S., Finn, D. P., Pickering, G., Pogatzki-Zahn, E., & Graven-Nielsen, T. (2021). Challenges and opportunities in translational pain research—An opinion paper of the working group on translational pain research of the European pain federation (EFIC). European Journal of Pain (London, England), 25(4), 731–756. https://doi.org/10.1002/ejp.1730
Nair, D. G., & Weiskirchen, R. (2024). Advanced In Vitro Models for Preclinical Drug Safety: Recent Progress and Prospects. Current Issues in Molecular Biology, 47(1), 7. https://doi.org/10.3390/cimb47010007
Orozco Morato, E., Knight, B., & Nair, L. S. (2022). Transcriptional profiling of neuronal ion channels in dorsal root ganglion–derived immortal cell line (F-11) under different culture conditions. In Vitro Models, 1(4–5), 385–395. https://doi.org/10.1007/s44164-022-00036-7
Pastori, V., D’Aloia, A., Blasa, S., & Lecchi, M. (2019). Serum-deprived differentiated neuroblastoma F-11 cells express functional dorsal root ganglion neuron properties. PeerJ, 7, e7951. https://doi.org/10.7717/peerj.7951
Perera, T. H., Lu, X., & Smith Callahan, L. A. (2020). Effect of Laminin Derived Peptides IKVAV and LRE Tethered to Hyaluronic Acid on hiPSC Derived Neural Stem Cell Morphology, Attachment and Neurite Extension. Journal of Functional Biomaterials, 11(1), 15. https://doi.org/10.3390/jfb11010015
Rende, M., Brizi, E., Conner, J., Treves, S., Censier, K., Provenzano, C., Taglialatela, G., Sanna, P. P., & Donato, R. (2000). Nerve growth factor (NGF) influences differentiation and proliferation of myogenic cells in vitro via TrKA. International Journal of Developmental Neuroscience: The Official Journal of the International Society for Developmental Neuroscience, 18(8), 869–885. https://doi.org/10.1016/s0736-5748(00)00041-1
Rosenberger, D. C., Blechschmidt, V., Timmerman, H., Wolff, A., & Treede, R.-D. (2020). Challenges of neuropathic pain: Focus on diabetic neuropathy. Journal of Neural Transmission, 127(4), 589–624. https://doi.org/10.1007/s00702-020-02145-7
Saeed, A. W., & Ribeiro-da-Silva, A. (2012). Non-peptidergic primary afferents are presynaptic to neurokinin-1 receptor immunoreactive lamina I projection neurons in rat spinal cord. Molecular Pain, 8, 64. https://doi.org/10.1186/1744-8069-8-64
Sharma, S., Hansen, J. T., & Notter, M. F. (1990). Effects of NGF and dibutyryl cAMP on neuronal differentiation of embryonal carcinoma cells. International Journal of Developmental Neuroscience: The Official Journal of the International Society for Developmental Neuroscience, 8(1), 33–45. https://doi.org/10.1016/0736-5748(90)90021-s
Sutton, K. G., Martin, D. J., Pinnock, R. D., Lee, K., & Scott, R. H. (2002). Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. British Journal of Pharmacology, 135(1), 257–265. https://doi.org/10.1038/sj.bjp.0704439
Yan, K., Gao, L.-N., Cui, Y.-L., Zhang, Y., & Zhou, X. (2016). The cyclic AMP signaling pathway: Exploring targets for successful drug discovery (Review). Molecular Medicine Reports, 13(5), 3715–3723. https://doi.org/10.3892/mmr.2016.5005
Published
2026-03-31
How to Cite
Nazwar, T., Laksono, R., Balafif, F., Wardhana, D., & Balafif, F. (2026). The F-11 Sensory Neuron Model: A Scalable In Vitro Platform for Neuropathic Pain and Drug Screening. Indonesian Journal of Life Sciences, 8(01), 111-131. https://doi.org/https://doi.org/10.54250/ijls.v8i01.290
Issue
Section
Pharmaceutical Science and Pharmacology
Articles published in Indonesian Journal of Life Sciences are licensed under a Creative Commons Attribution-ShareAlike 4.0 International license. You are free to copy, transform, or redistribute articles for any lawful purpose in any medium, provided you give appropriate credit to the original author(s) and Indonesian Journal Life of Sciences, link to the license, indicate if changes were made, and redistribute any derivative work under the same license. Copyright on articles is retained by the respective author(s), without restrictions. A non-exclusive license is granted to Indonesian Journal Life of Sciences to publish the article and identify itself as its original publisher, along with the commercial right to include the article in a hardcopy issue for sale to libraries and individuals. By publishing in Indonesian Journal Life of Sciences, authors grant any third party the right to use their article to the extent provided by the Creative Commons Attribution-ShareAlike 4.0 International license.
