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Clinical and pre-clinical research is beginning to highlight the beneficial role that rehabilitative therapies such as locomotor training can have not only on functional recovery but also on chronic pain management. Our group has previously developed an intensive locomotor training (ILT) treadmill protocol on rats that reduced SCI neuropathic pain symptoms for at least 3 months. We have extended these findings in the current study to evaluate the ability of regular ILT regimen over a 2 year period post-SCI to maintain neuropathic pain reduction. To assess this, the rat clip compression SCI model (T7\/8) was used and treadmill training was initiated starting 4 weeks after SCI and continuing through the duration of the study. Results showed continued suppression of SCI neuropathic pain responses (reduced mechanical, heat, and cold hypersensitivity throughout the entire time course of the study). In contrast, non-exercised rats showed consistent and sustained neuropathic pain responses during this period. In addition, prolonged survival and improved locomotor outcomes were observed in rats undergoing ILT as the study longevity progressed. Potential contributory mechanisms underlying beneficial effects of ILT include reduced inflammation and restoration of anti-nociceptive inhibitory processes as indicated by neurochemical assays in spinal tissue of remaining rats at 2 years post-SCI. The benefits of chronic ILT suggest that long-term physical exercise therapy can produce powerful and prolonged management of neuropathic pain, partly through sustained reduction of spinal pathological processes.<\/jats:p>","DOI":"10.1089\/neu.2020.7378","type":"journal-article","created":{"date-parts":[[2020,11,21]],"date-time":"2020-11-21T00:52:40Z","timestamp":1605919960000},"page":"789-802","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":21,"title":["Intensive Locomotor Training Provides Sustained Alleviation of Chronic Spinal Cord Injury-Associated Neuropathic Pain: A Two-Year Pre-Clinical Study"],"prefix":"10.1177","volume":"38","author":[{"given":"Elizabeth A.","family":"Dugan","sequence":"first","affiliation":[{"name":"The Miami Project to Cure Paralysis, University of Miami, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Schachner","sequence":"additional","affiliation":[{"name":"The Miami Project to Cure Paralysis, University of Miami, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislava","family":"Jergova","sequence":"additional","affiliation":[{"name":"The Miami Project to Cure Paralysis, University of Miami, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Sagen","sequence":"additional","affiliation":[{"name":"The Miami Project to Cure Paralysis, University of Miami, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1053\/apmr.2001.21855"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.sc.3101161"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.60.11.1524"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejp.905"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2018.07.003"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/AJP.0000000000000675"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/ptj\/80.7.688"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmr.2007.02.002"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-52137-8.00016-4"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2012.04.032"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(86)90094-4"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)90751-X"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.sc.3100590"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.NPT.0000282245.31158.09"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01004.2004"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2013.08.018"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2010.02.010"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000001945"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmr.2007.07.010"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/sc.2010.167"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.02.013"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh160"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2018.5819"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2014.04.026"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2017.5431"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000422"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2017.5537"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1177\/1545968314562110"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2013.3082"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2014.3692"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2020.113208"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X14666160330105132"},{"issue":"30","key":"e_1_3_4_34_2","first-page":"898","article-title":"Functional recovery from neural stem\/progenitor cell transplantation combined with treadmill training in mice with chronic spinal cord injury","volume":"6","author":"Tashiro S.","year":"2016","unstructured":"Tashiro S., , Nishimura S., , Iwai H., , Sugai K., , Zhang L., , Shinozaki M., , Iwanami A., , Toyama Y., , Liu M., , Okano H., , and Nakamura M. 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