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The goal of these studies was to determine whether the blood-borne serine protease thrombin also crosses a permeable BSCB, contributing to nociception through its activation of protease-activated receptor-1 (PAR1).<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>METHODS<\/jats:title>\n<jats:p>A 15-minute C-7 nerve root compression, which induces BSCB breakdown and painful behaviors by Day 1, was administered in the rat (n = 10); sham operation (n = 11) and a 3-minute compression (n = 10) that does not induce sensitivity were administered as controls. At Day 1 after root compression, spinal cord tissue was co-immunolabeled for fibrin\/fibrinogen, the enzymatic product of thrombin, and IgG, a serum protein, to determine whether thrombin acts in areas of BSCB breakdown. To determine whether spinal thrombin and PAR1 contribute to hyperalgesia after compression, the thrombin inhibitor hirudin and the PAR1 antagonist SCH79797, were separately administered intrathecally before compression injuries (n = 5\u20137 per group). Rat thrombin was also administered intrathecally with and without SCH79797 (n = 6 per group) to determine whether spinal thrombin induces hypersensitivity in na\u00efve rats through PAR1.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>RESULTS<\/jats:title>\n<jats:p>Spinal fibrin(ogen) was elevated at Day 1 after root compression in regions localized to BSCB breakdown and decreased in those regions by Day 7. Blocking either spinal thrombin or PAR1 completely prevented compression-induced hyperalgesia for 7 days. Intrathecal thrombin induced transient pain that was prevented by blocking spinal PAR1 before its injection.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>CONCLUSIONS<\/jats:title>\n<jats:p>The findings of this study suggest a potent role for spinal thrombin and its activation of PAR1 in pain onset following neuropathic injury.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2016.9.spine16501","type":"journal-article","created":{"date-parts":[[2017,1,6]],"date-time":"2017-01-06T15:03:19Z","timestamp":1483714999000},"page":"532-541","source":"Crossref","is-referenced-by-count":5,"title":["The role of spinal thrombin through protease-activated receptor 1 in hyperalgesia after neural injury"],"prefix":"10.3171","volume":"26","author":[{"given":"Jenell R.","family":"Smith","sequence":"first","affiliation":[{"name":"Departments of Bioengineering and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth A.","family":"Winkelstein","sequence":"additional","affiliation":[{"name":"Departments of Bioengineering and"},{"name":"Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1754","reference":[{"key":"b1-spine16501","series-title":"Pain","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/0304-3959(88)90198-4","article-title":"Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain","volume":"33","author":"Arn\u00e9r S,","year":"1988","unstructured":"Arn\u00e9r S, Meyerson BA: Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. 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