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The neuropathic pain triad: neurons, immune cells and glia

Abstract

Nociceptive pain results from the detection of intense or noxious stimuli by specialized high-threshold sensory neurons (nociceptors), a transfer of action potentials to the spinal cord, and onward transmission of the warning signal to the brain. In contrast, clinical pain such as pain after nerve injury (neuropathic pain) is characterized by pain in the absence of a stimulus and reduced nociceptive thresholds so that normally innocuous stimuli produce pain. The development of neuropathic pain involves not only neuronal pathways, but also Schwann cells, satellite cells in the dorsal root ganglia, components of the peripheral immune system, spinal microglia and astrocytes. As we increasingly appreciate that neuropathic pain has many features of a neuroimmune disorder, immunosuppression and blockade of the reciprocal signaling pathways between neuronal and non-neuronal cells offer new opportunities for disease modification and more successful management of pain.

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Figure 1: Immune and glial cell responses to peripheral nerve injury.

Kim Caesar

Figure 2: Inflammatory changes associated with wallerian degeneration.

Kim Caesar

Figure 3: Immune response in the DRG.

Kim Caesar

Figure 4: Recruitment and activation of spinal microglia and astrocytes.

Kim Caesar

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Acknowledgements

Supported by grants from the US National Institute of Neurological Disorders and Stroke (J.S., C.J.W.) and the US National Institute of Dental and Craniofacial Research (C.J.W.).

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Scholz, J., Woolf, C. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci 10, 1361–1368 (2007). https://doi.org/10.1038/nn1992

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