{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T01:52:24Z","timestamp":1770774744381,"version":"3.50.0"},"reference-count":64,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,1,9]],"date-time":"2012-01-09T00:00:00Z","timestamp":1326067200000},"content-version":"vor","delay-in-days":1044,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>Background:<\/jats:italic> Tibia fracture in rats evokes chronic hindpaw warmth, edema, allodynia, and regional osteopenia, a syndrome resembling complex regional pain syndrome (CRPS). Previous studies suggest that the pathogenesis of some of these changes involves an exaggerated regional inflammatory response to injury and we postulated that inflammatory cytokines contribute to the development of CRPS\u2010like changes after fracture.<\/jats:p><jats:p><jats:italic>Methods:<\/jats:italic> The distal tibia was fractured and the hindlimb casted for 4 weeks. The rats were given drinking water with or without the cytokine inhibitor pentoxifylline (PTX) starting the day before fracture and continuing for 4 weeks, after which time the cast was removed and multiple assays were performed in the hindpaw. PCR and immunoassays were used to evaluate changes in cytokine expression. Bilateral hindpaw thickness, temperature, and nociceptive thresholds were determined, and bone microarchitecture was measured by microcomputed tomography (\u03bcCT).<\/jats:p><jats:p><jats:italic>Results:<\/jats:italic> Tibia fracture chronically up\u2010regulated TNF\u03b1, IL\u20101\u03b2 and IL\u20106 mRNA and protein levels in hindpaw skin and PTX treatment significantly reduced the mRNA expression and cytokine protein levels for all these cytokines. PTX inhibited the nociceptive sensitization and some vascular changes, but had insignificant effects on most of the bone\u2010related parameters measured in these studies. Immunostaining of hindpaw skin was negative for immunocyte infiltration at 4 weeks post\u2010fracture.<\/jats:p><jats:p><jats:italic>Conclusions:<\/jats:italic> These results suggest that pro\u2010inflammatory cytokines contribute to the nociceptive and vascular sequelae of fracture and that PTX treatment can reverse these CRPS\u2010like changes.<\/jats:p>","DOI":"10.1016\/j.ejpain.2008.04.014","type":"journal-article","created":{"date-parts":[[2008,6,13]],"date-time":"2008-06-13T16:24:08Z","timestamp":1213374248000},"page":"253-262","source":"Crossref","is-referenced-by-count":54,"title":["Pentoxifylline attenuates nociceptive sensitization and cytokine expression in a tibia fracture rat model of complex regional pain syndrome"],"prefix":"10.1002","volume":"13","author":[{"given":"Tzuping","family":"Wei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilya","family":"Sabsovich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian\u2010Zhi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyou","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenwu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Geis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Sommer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wade S.","family":"Kingery","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,1,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(82)90401-X"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2005.04.013"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002510050032"},{"key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1302\/0301-620X.72B1.2298766","article-title":"Features of algodystrophy after colles' fracture","volume":"72","author":"Atkins R.M.","year":"1990","journal-title":"J Bone Joint Surg B"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/32.1.46"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/33.3.240"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03403529"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.17.1.f132"},{"key":"e_1_2_8_10_1","first-page":"685","volume-title":"Textbook of Pain","author":"Blumberg H.","year":"1994"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.19.8964"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409225102"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1213\/01.ANE.0000113235.88534.48"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700701"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri802"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2004.07.004"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.14.9.1093"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00301260"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199902000-00022"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2003.12.010"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2005.12.022"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-003-0490-y"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/09629350210307"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2003.12.006"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2003.11.013"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1743"},{"issue":"4","key":"e_1_2_8_27_1","first-page":"427","article-title":"Pentoxifylline inhibits endotoxin\u2010induced NF\u2010kappa B activation and associated production of proinflammatory cytokines","volume":"34","author":"Ji Q.","year":"2004","journal-title":"Ann Clin Lab Sci"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.3.1431"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(02)00467-0"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(00)00395-1"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V74.1.1.1"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(03)00163-8"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2006.11.022"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1213\/01.ANE.0000132974.32249.C8"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2004.05.007"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01260988"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2007.01.013"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5444.1558"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(93)90144-E"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.159.11.5450"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1159\/000098223"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.142.11.4673"},{"issue":"11","key":"e_1_2_8_43_1","doi-asserted-by":"crossref","first-page":"3622","DOI":"10.1016\/S0021-9258(19)42618-5","article-title":"Stimulation and desensitization of macrophage adenylate cyclase by prostaglandins and catecholamines","volume":"249","author":"Remold\u2010O'Donnell E.","year":"1974","journal-title":"J Biol Chem"},{"issue":"2","key":"e_1_2_8_44_1","first-page":"137","article-title":"Studies on osteoporoses. XI. Effects of a methylxanthine derivative. A preliminary report","volume":"14","author":"Robin J.C.","year":"1983","journal-title":"J Med"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.028233"},{"issue":"3","key":"e_1_2_8_46_1","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1302\/0301-620X.75B3.8496220","article-title":"Algodystrophy and osteoporosis after tibial fractures","volume":"75","author":"Sarangi P.P.","year":"1993","journal-title":"J Bone Joint Surg Br"},{"key":"e_1_2_8_47_1","doi-asserted-by":"crossref","unstructured":"J.S.Smolen D.Aletaha M.Koeller M.H.Weisman P.EmeryNew therapies for treatment of rheumatoid arthritis.Lancet2007.","DOI":"10.1016\/S0140-6736(07)60784-3"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(88)81271-3"},{"issue":"3","key":"e_1_2_8_49_1","doi-asserted-by":"crossref","first-page":"775","DOI":"10.4049\/jimmunol.138.3.775","article-title":"Tumor necrosis factors alpha and beta induce osteoblastic cells to stimulate osteoclastic bone resorption","volume":"138","author":"Thomson B.M.","year":"1987","journal-title":"J Immunol"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.164.1.104"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2006.12.014"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(99)00035-4"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(02)00839-6"},{"key":"e_1_2_8_54_1","doi-asserted-by":"crossref","unstructured":"N.Uceyler A.Tscharke C.SommerEarly cytokine expression in mouse sciatic nerve after chronic constriction nerve injury depends on calpain.Brain Behav Immun2007.","DOI":"10.1016\/j.bbi.2006.10.003"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705999"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)92877-V"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1254\/jjp.79.477"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-198734010-00003"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/124.3.587"},{"issue":"8","key":"e_1_2_8_60_1","first-page":"S58","article-title":"The treatment of postherpetic neuralgia","volume":"45","author":"Waston C.P.","year":"1995","journal-title":"Neurology"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(00)00445-0"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701148"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(00)00419-7"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3597"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0171-2985(11)80356-6"}],"container-title":["European Journal of Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.ejpain.2008.04.014","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.ejpain.2008.04.014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T05:14:38Z","timestamp":1697433278000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1016\/j.ejpain.2008.04.014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3]]},"references-count":64,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2009,3]]}},"alternative-id":["10.1016\/j.ejpain.2008.04.014"],"URL":"https:\/\/doi.org\/10.1016\/j.ejpain.2008.04.014","archive":["Portico"],"relation":{},"ISSN":["1090-3801","1532-2149"],"issn-type":[{"value":"1090-3801","type":"print"},{"value":"1532-2149","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,3]]}}}