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Endocannabinoids serve as retrograde signaling messengers in <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content>ergic and glutamatergic synapses, as well as modulators of postsynaptic transmission, that interact with other neurotransmitters. Physiological stimuli and pathological conditions lead to differential increases in brain endocannabinoids that regulate distinct biological functions. Furthermore, endocannabinoids modulate neuronal, glial, and endothelial cell function and exert neuromodulatory, anti\u2010excitotoxic, anti\u2010inflammatory, and vasodilatory effects. Analgesia is one of the principal therapeutic targets of cannabinoids. Cannabinoid analgesia is based on the suppression of spinal and thalamic nociceptive neurons, but peripheral sites of action have also been identified. The chronic pain that occasionally follows peripheral nerve injury differs fundamentally from inflammatory pain and is an area of considerable unmet therapeutic need. Over the last years, considerable progress has been made in understanding the role of the <jats:styled-content style=\"fixed-case\">ES<\/jats:styled-content> in the modulation of pain. Endocannabinoids have been shown to behave as analgesics in models of both acute nociception and clinical pain such as inflammation and painful neuropathy. The framework for such analgesic effects exists in the CB receptors, which are found in areas of the nervous system important for pain processing and in immune cells that regulate the neuro\u2010immune interactions that mediate the inflammatory hyperalgesia. The purpose of this review is to present the available research and clinical data, up to date, regarding the ES and its role in pain modulation, as well as its possible therapeutic perspectives.<\/jats:p>","DOI":"10.1111\/fcp.12008","type":"journal-article","created":{"date-parts":[[2013,1,2]],"date-time":"2013-01-02T08:13:52Z","timestamp":1357114432000},"page":"64-80","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["The role of endocannabinoids in pain modulation"],"prefix":"10.1111","volume":"27","author":[{"given":"Panagiotis","family":"Zogopoulos","sequence":"first","affiliation":[{"name":"First Department of Pathology, Medical School University of Athens 75 Mikras Asias Street Goudi, 11527 Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Vasileiou","sequence":"additional","affiliation":[{"name":"First Department of Pathology, Medical School University of Athens 75 Mikras Asias Street Goudi, 11527 Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efstratios","family":"Patsouris","sequence":"additional","affiliation":[{"name":"First Department of Pathology, Medical School University of Athens 75 Mikras Asias Street Goudi, 11527 Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stamatios E.","family":"Theocharis","sequence":"additional","affiliation":[{"name":"First Department of Pathology, Medical School University of Athens 75 Mikras Asias Street Goudi, 11527 Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,1,2]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1208\/aapsj070364"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/156800705774322111"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(00)00615-4"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agh110"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2009.12.005"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/346561a0"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001090000177"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1470919"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2007.06.031"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/138955706776073466"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00236.2007"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707569"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1247"},{"key":"e_1_2_6_15_1","first-page":"129","article-title":"Characterization and localization of cannabinoid receptors in brain: an in vitro technique using slide\u2010mounted tissue sections","volume":"112","author":"Herkenham M.","year":"1991","journal-title":"NIDA Res. 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