Human sensory neuron-like cells and glycated collagen matrix as a model for the screening of analgesic compounds

Translated title
Células semelhantes a neurônios sensoriais humanos e matriz de colágeno glicado como modelo para a triagem de compostos analgésicos

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Article
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English
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Open access
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CC BY
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Abstract
Increased collagen-derived advanced glycation end-products (AGEs) are consistently related to painful diseases, including osteoarthritis, diabetic neuropathy, and neurodegenerative disorders. We have recently developed a model combining a two-dimensional glycated extracellular matrix (ECM-GC) and primary dorsal root ganglion (DRG) that mimicked a pro-nociceptive microenvironment. However, culturing primary cells is still a challenge for large-scale screening studies. Here, we characterized a new model using ECM-GC as a stimulus for human sensory-like neurons differentiated from SH-SY5Y cell lines to screen for analgesic compounds. First, we confirmed that the differentiation process induces the expression of neuron markers (MAP2, RBFOX3 (NeuN), and TUBB3 (β-III tubulin), as well as sensory neuron markers critical for pain sensation (TRPV1, SCN9A (Nav1.7), SCN10A (Nav1.8), and SCN11A (Nav1.9). Next, we showed that ECM-GC increased c-Fos expression in human sensory-like neurons, which is suggestive of neuronal activation. In addition, ECM-GC upregulated the expression of critical genes involved in pain, including SCN9A and TACR1. Of interest, ECM-GC induced substance P release, a neuropeptide widely involved in neuroinflammation and pain. Finally, morphine, the prototype opiate, decreased ECM-GC-induced substance P release. Together, our results suggest that we established a functional model that can be useful as a platform for screening candidates for the management of painful conditions.
Reference
Búfalo MC, Almeida MES, Jensen JR, De Ocesano-Pereira C, Lichtenstein F, Picolo G, et al. Human sensory neuron-like cells and glycated collagen matrix as a model for the screening of analgesic compounds. Cells. 2022 Jan;11(2):247. doi:10.3390/cells11020247.
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https://repositorio.butantan.gov.br/handle/butantan/4108
URL
https://doi.org/10.3390/cells11020247
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Issue Date
2022


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