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: 16.1). 12/2007; 10(11):1361-8. DOI: 10.1038/nn1992
Source: PubMed


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
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    • "These elements release factors (TNFα, prostaglandins, NGF) that initiate and maintain sensory anomalies after injury. They act on the axons or being retrogradely transported to cell bodies in the DRG where they can modify the gene expression (Scholz & Woolf, 2007). "
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    • "Inflammatory activation of chemosensitive nerve endings in muscles and joints may induce disturbed activity of muscle spindles and, in turn, diminished proprioceptive feedback (Sj€ olander, Johansson, & Djupsj€ obacka, 2002). In chronic low back pain (CLBP), Schwann cells of afferent nerves are locally dedifferentiated and the dorsal root in the spinal ganglion and the gyrus postcentralis are sensitized (Scholz & Woolf, 2007). Evoked muscle stiffness and deficiencies in muscle coordination due to diminished proprioceptive feedback are common symptoms in patients suffering from chronic (low back) pain (Sj€ olander et al., 2002). "
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    ABSTRACT: Increased gait variability is common in chronic low back pain patients, which is a sign of their diminished proprioceptive feedback. When proprioceptive information is reduced, vision partly takes over the role of proprioception. Therefore, a loss of visual feedback would have a more negative effect in individuals with diminished proprioception. To test this hypothesis, 14 healthy individuals and 14 chronic low back pain patients walked with and without impairment goggles manipulating visual feedback. The variability of stride time, stride length, and minimum foot clearance was evaluated. The authors observed an interaction effect regarding minimum foot clearance variability indicating that pain patients showed higher gait variability with manipulated visual feedback. Reduced vision may cause exceeded tripping risk in individuals with diminished proprioception.
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    • "Here was a great example of Louis being well before his time; the MOM suggested that there was a role of the immune system in pain not merely in response to tissue damage but also during nociceptive processing. There is now a massive body of work (McMahon et al 2005; Marchand et al 2007; Scholz & Woolf 2007; Thacker et al 2007) that has confirmed that the neuro-immune interactions are critical in the development and maintenance of pain. Importantly, Louis hypothesised that these interactions are also operational in nonpain states, i.e. during homeostasis and development; and we now know that they are. "
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    ABSTRACT: There is much that I could say about Louis and I am fortunate to have had the opportunity elsewhere (see http:// and news/2014/10/13/physio-14-speakers-praise-work-louis-gifford- pain-management-pioneer). I want this account to be about Louis’ ongoing contribution to our understanding of pain and to demonstrate that his ideas will continue to have impact for many years to come. I have had the pleasure of working directly with several “greats” in the world of pain, most notably Professor Pat Wall and Professor Steve McMahon. What they had/have and Louis shared, was the ability to see way into the future developments of pain research and somehow get their finger on a pulse that hadn’t yet started.
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