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GLIA AND DISEASE
REVIEW
http://www.nature.com/natureneuroscience
Web End = The neuropathic pain triad: neurons, immune cells and glia
http://www.nature.com/natureneuroscience
Joachim Scholz & Clifford J Woolf
200 7
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 modication and more successful management of pain.
Pain has long been regarded as the unpleasant sensory consequence of neuronal activity in specic nociceptive pathways that is triggered by noxious stimuli, inammation, or damage to the nervous system. This is certainly true for acute nociceptive pain, such as the pain elicited by a pinprick or excessive heat. However, it is now clear that neurons are not the only players that drive the establishment and maintenance of common clinical pain states. In this review we focus on immune and glial cell responses to peripheral nerve injury and how they alter neuronal function in the peripheral and central nervous systems.Recognition of the critical involvement of immune cells and glia in the pathophysiological changes after nerve injury offers a completely new treatment approach, one that is certainly needed because most analgesic drugs lack satisfactory efcacy for neuropathic pain and produce undesirable side effects1. Neuropathic pain management is currently aimed only at reducing symptoms, generally by suppressing neuronal activity. In contrast, modulating the immune response to nerve injury and targeting glia may provide opportunities for disease modication by aborting neurobiological alterations that support the development of persistent pain.
Peripheral nerve injury provokes a reaction in peripheral immune cells and glia at several different anatomical locations: macrophages and Schwann cells facilitate the wallerian...