New Solution: Neuroinflammation and nociception in a dish

Research in the field of pain and neuroinflammation is currently conducted either in vivo or on isolated cells cultured in vitro. Although working in vivo offers the obvious advantage of maintaining an intact neuronal circuitry, this type of approach is technically very demanding and suffers from a high degree of variability in the nociceptive responses between individuals and sets of experiments. Additionally, drug bioavailability can be difficult to control and certain substances do not pass the blood-brain barrier, thus requiring spinal intrathecal administration, increasing complexity and welfare burden. These experiments, usually in rodents, not only require inducing pain by different physical or chemical approaches, but also, specifically when neuropathic or chronic pain is studied, the generation of nerve injury resulting in long lasting pain hypersensitivity. Many of these shortcomings can be overcome using cultured primary neurons and/or neuronal cell lines, but circuitries are lost by this approach, rendering it unsuitable to the study of cell-to-cell communication and modulation of neural signals.

Addressing some of these difficulties, researchers from the Department of Veterinary Sciences, University of Turin, Italy have developed acute and organotypically cultured spinal cord slices and demonstrated that they can provide unique insight into the central mechanisms of nociception and neuroinflammation. These innovative spinal cord slice platforms (SCSPs) offer several advantages for studying the structural, physiological and pharmacological properties of pain circuits, including:

  • They retain the cytoarchitecture of the tissue of origin;
  • They provide good experimental access and allow precise control of extracellular environments, facilitating research aiming to establish clear correlations between structure and function;
  • They can be easily subjected to a surrogate inflammatory challenge and the response of the synapses between first and second order nociceptive neurons can be monitored using multiple endpoints;
  • The system can be manipulated by genetic engineering using a physical transfection method (gene-gun) that, at least in part, avoids the need to generate novel transgenic strains.

These SCSPs are now being showcased through CRACK IT Solutions to engage with (bio)pharmaceutical and academic partners able to provide candidate pain-controlling drugs/molecules to validate the platform for preclinical drug development and precision medicine, and to explore the utility of the slice model for investigating other disease models.

Using SCSPs has the potential to reduce to one fourth the number of animals used in studying pain biology. Multiple slices (up to four) from a single animal can be cultured in each well of a multi-well plate, and subjected to different experimental challenges. A typical in vivo approach would use eight mice per group in four groups, therefore SCSPs have the potential to reduce the number of mice used from 32 to eight – click here for further information. Furthermore, SCSPs can be transiently transfected to express one or more proteins of interest, removing the requirement to breed transgenic animals for some experiments.

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