title: Upregulation of inflammatory mediators in a model of chronic pain after spinal cord injury.
abstract: Chronic neuropathic pain is a disabling condition observed in large number of individuals following spinal cord injury (SCI). Recent progress points to an important role of neuroinflammation in the pathogenesis of central neuropathic pain. The focus of the present study is to investigate the role of proinflammatory molecules IL-1β, TNF-α, MCP-1, MMP-9 and TIMP-1 in chronic neuropathic pain in a rodent model of SCI. Rats were subjected to spinal cord contusion using a controlled linear motor device with an injury epicenter at T10. The SCI rats had severe impairment in locomotor function at 7 days post-injury as assessed by the BBB score. The locomotor scores showed significant improvement starting at day 14 and thereafter showed no further improvement. The Hargreaves' test was used to assess thermal hyperalgesia for hindpaw, forepaw and tail. A significant reduction in withdrawal latency was observed for forepaw and tail of SCI rats at days 21 and 28, indicating the appearance of thermal hyperalgesia. Changes in expression of mRNAs for IL-1β, TNF-α, MCP-1, MMP-9 and TIMP-1 were assessed using real-time polymerase chain reaction in spinal cord including the injury epicenter along with regions above and below the level of lesion at day 28 post-injury. A significant increase was observed in the expression of MCP-1, TNF-α, TIMP-1 and IL-1β in the injury epicenter, whereas only TIMP-1 was upregulated in the area below the injury epicenter. The results of the study suggest that prolonged upregulation of inflammatory mediators might be involved in chronic neuropathic pain in SCI, and that TIMP-1 may play a role in maintenance of chronic below level pain.
authors.affiliation: Steve Palermo Nerve Regeneration Laboratory, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
authors.forename: Rajat
authors.initials: R
authors.lastname: Sandhir
authors.forename: Eugene
authors.initials: E
authors.lastname: Gregory
authors.forename: Yong-Yue
authors.initials: YY
authors.lastname: He
authors.forename: Nancy E J
authors.initials: NE
authors.lastname: Berman
mesh_terms: D000818:Animals; D001483:Base Sequence; D002908:Chronic Disease; D017931:DNA Primers; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D017931:DNA Primers; D018836:Inflammation Mediators