Techniques for Multiscale Neuronal Regulation via Therapeutic Materials and Drug Design

Neurotrauma is a common source for a host of neurological disorders, including chronic pain. Pathological changes underlying neural injury and pain are complex due to the multiscale spatiotemporal nature of the nervous system and its response to insults. Understanding the combined influence of tissue mechanics, neuronal and glial activation, and molecular processes on the development and maintenance of pain has recently gained attention. The growing knowledge about nociceptive mechanisms has inspired the design of novel therapeutic materials and compounds for neuronal regulation. Primary mechanical insults and secondary inflammatory responses can induce morphological changes, electrophysiological abnormalities, and altered neurotransmitter release associated with neuronal dysfunction, degeneration, and/or death in both central and peripheral nervous systems. Such responses in afferent and spinal dorsal horn neurons directly and indirectly potentiate pain. Using separate radiculopathy and joint pain models, the mechanical, nociceptive, and inflammatory aspects of pain are reviewed. In that context, biomaterials and compounds with material advantages, neuroprotective benefits, or anti-inflammatory effects to mitigate pain are identified. Several promising techniques to promote neuronal survival and axonal regeneration after injury, including bioactive scaffolds, blocking growth-inhibitory molecules, and active drug delivery, are highlighted. Similar biomaterials-based strategies and molecular intervention have shown promise in attenuating various types of pain. Advancing these and other approaches will help advance and deepen the mechanistic understanding underlying trauma-induced pain across different length scales.