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We have hypothesized that changes in extracellular proteolysis in the dorsal horn is involved in neuroplastic changes in the dorsal horn after nerve injury. Tissue type plasminogen activator (tPA) is a well\u2010known extracellular serine protease and is involved in the modification of the extracellular matrix, which leads to neuroplastic changes such as long\u2010term potentiation in the hippocampus. In the present study, we found a marked induction of tPA in activated astrocytes following L4\/5 root injury and a resultant increase of proteolytic enzymatic activity in the dorsal horn. We also examined the involvement of tPA activity on mechanical hypersensitivity using a root ligation model which has been used for investigating radiculopathy pain behavior. Intrathecal and continuous administration of tPA inhibitor, tPA\u2010STOP, suppressed root ligation\u2010induced mechanical allodynia in a dose\u2010dependent manner during an early stage of injury (0\u20134 days). In contrast, the delayed administration of tPA\u2010STOP during the chronic stage of injury (10 days) did not affect pain behavior. These data suggest an important contribution of astrocytes in the dorsal horn to the pathophysiology of radiculopathy pain, and astrocyte\u2010derived tPA and the proteolytic activity in the dorsal horn may be one of the essential factors involved in pain following root injury. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20483","type":"journal-article","created":{"date-parts":[[2007,2,13]],"date-time":"2007-02-13T22:12:21Z","timestamp":1171404741000},"page":"595-603","source":"Crossref","is-referenced-by-count":32,"title":["Tissue type plasminogen activator induced in rat dorsal horn astrocytes contributes to mechanical hypersensitivity following dorsal root injury"],"prefix":"10.1002","volume":"55","author":[{"given":"Toyoko","family":"Kozai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Yamanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Obata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimiko","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Mashimo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Noguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,2,13]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01645-5"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2002.004"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80597-8"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(76)90899-4"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(84)90210-3"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510645103"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80483-3"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200307068"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(03)00035-6"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00318731"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1999.7065"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903610407"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.11030"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1090-3801(97)90069-0"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100180618"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902230111"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-13-04891.2001"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-200005150-00003"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(00)00281-5"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00906-8"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000176239.72928.00"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902100404"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2005.02.009"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199807)23:3<221::AID-GLIA5>3.0.CO;2-7"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19980406)393:2<135::AID-CNE1>3.0.CO;2-3"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3139-06.2006"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-05-02003.2000"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2507-05.2005"},{"key":"e_1_2_6_30_1","doi-asserted-by":"crossref","first-page":"4117","DOI":"10.1523\/JNEUROSCI.23-10-04117.2003","article-title":"Differential 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