Article

The neuropathic pain triad: Neurons, immune cells, and glia

Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Nature Neuroscience (Impact Factor: 14.98). 12/2007; 10(11):1361-8. DOI: 10.1038/nn1992
Source: PubMed

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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Available from: Clifford J Woolf, Aug 30, 2015
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    • "Peripheral nerves are the source of almost all forms of neuropathic pain. Neuropathic pain is a complex syndrome resulting from many different forms of peripheral nerve damage, such as traumatic nerve damage, diabetes, and infections, as well as immune system and metabolic diseases [6]. For decades, a neuron-centered argument has been frequently used to explain the pathophysiology of chronic pain; however, recent studies have shifted attention towards a neuroimmune interaction. "
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    • "mechanisms. These neuronal pathophysiological mechanisms are being supplemented by an appreciation for the role of central immune signaling, such that neuropathic pain, for instance, is now considered as a neuroimmune disorder [3] (Fig. 1). "
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    • "Chronic pain that resulted from inflammation, infection, nerve injury , or cancer is a major public health problem worldwide. Neuroinflammation , which is mediated by a variety of inflammatory mediators, including cytokines and chemokines, has been recently recognized to play an important role in the pathogenesis of chronic pain (Mennicken et al., 1999; Miller et al., 2008; Scholz and Woolf, 2007; White et al., 2007). Chemokines are a family of small (8–12 kDa) proteins involved in the modulation of numerous biological functions, including leukocyte migration and activation, cell adhesion, and T cell activation via Gprotein-coupled receptors (GPCR). "
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