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Drugs against long-term pain are today directed against increased neuronal excitability, mostly with less success.<\/jats:p>\n                  <jats:p>\n                    An injury often starts with acute physiological pain, which becomes inflammatory, nociceptive, or neuropathic, and may be transferred into long-term pain. Recently a low-grade inflammation was identified in the spinal cord and along the pain pathways to thalamus and the parietal cortex. This neuroinflammation is due to activation of glial cells, especially microglia, with production of cytokines and other inflammatory mediators within the CNS. Additionally, substances released to the blood from the injured region influence the blood\u2013brain barrier, and give rise to an increased permeability of the tight junctions of the capillary endothelial cells, leading to passage of blood cells into the CNS. These cells are transformed into reactive microglia. If the inflammation turns into a pathological state the astrocytes will be activated. They are coupled into networks and respond to substances released by the capillary endothelial cells, to cytokines released from microglia, and to neurotransmitters and peptides released from neurons. As the astrocytes occupy a strategic position between the vasculature and synapses, they monitor the neuronal activity and transmitter release. Increased release of glutamate and ATP leads to disturbances in Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signalling, increased production of cytokines and free radicals, attenuation of the astrocyte glutamate transport capacity, and conformational changes in the astrocytic cytoskeleton, the actin filaments, which can lead to formation and rebuilding of new synapses. New neuronal contacts are established for maintaining and spreading pain sensation with the astrocytic networks as bridges. Thereby the glial cells can maintain the pain sensation even after the original injury has healed, and convert the pain into long-term by altering neuronal excitability. It can even be experienced from other parts of the body. As astrocytes are intimate co-players with neurons in the CNS, more knowledge on astrocyte responses to inflammatory activators may give new insight in our understanding of mechanisms of low-grade inflammation underlying long-term pain states and pain spreading. Novel treatment strategies would be to restore glial cell function and thereby attenuate the neuroinflammation.\n                  <\/jats:p>","DOI":"10.1016\/j.sjpain.2010.01.002","type":"journal-article","created":{"date-parts":[[2010,3,23]],"date-time":"2010-03-23T06:55:41Z","timestamp":1269327341000},"page":"67-72","source":"Crossref","is-referenced-by-count":47,"title":["Long-term pain, neuroinflammation and glial activation"],"prefix":"10.1515","volume":"1","author":[{"given":"Elisabeth","family":"Hansson","sequence":"first","affiliation":[{"name":"Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy , University of Gothenburg , Per Dubbsgatan 14, 1tr, SE 413 45 , Gothenburg , Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2010,4,1]]},"reference":[{"key":"2025120909551187925_j_j.sjpain.2010.01.002_ref_001","doi-asserted-by":"crossref","unstructured":"Scholz J, Woolf CJ. 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