Immune and Glial Cells in Pain and Their Interactions with Nociceptive Neurons
While pain is sensed and conducted by neurons, including primary sensory neurons (nociceptors) and spinal cord pain transmission neurons, mounting evidence suggests that non-neuronal cells such as immune cells and glial cells in the peripheral nervous system (PNS) and central nervous system (CNS) play active roles in the pathogenesis and resolution of pain. We review how immune cells and glial cells interact with peripheral and central nociceptive neurons by secreting neuroactive signaling molecules (neuromodulators), leading to altered pain sensitivity. It is generally believed that chronic pain is maintained by central sensitization, that is, increased synaptic and neuronal responsiveness (synaptic or neural plasticity) in central pain pathways, after painful injuries and insults. Recent studies also suggest that central sensitization is driven by neuroinflammation. We also discuss how immune cells and glial cells regulate central sensitization and neuroinflammation in the context of chronic pain.
