{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:09:24Z","timestamp":1791299364608,"version":"4.1.0"},"reference-count":26,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2010,4,27]],"date-time":"2010-04-27T00:00:00Z","timestamp":1272326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The calpain inhibitor MDL-28710 blocks the early local pro-inflammatory cytokine gene expression in mice after chronic constriction nerve injury (CCI). One-hundred-thirteen wild type mice of C57Bl\/6J background received CCI of the right sciatic nerve. Mechanical paw withdrawal thresholds and thermal withdrawal latencies were investigated at baseline and at 1, 3, and 7 days after CCI. Three application regimens were used for MDL-28170: a) single injection 40 min before CCI; b) serial injections of MDL-28170 40 min before and up to day three after CCI; c) sustained application via intraperitoneal osmotic pumps. The control animals received the vehicle DMSO\/PEG 400. The tolerable dose of MDL-28170 for mice was 30 mg\/kg body weight, higher doses were lethal within the first hours after application. Mechanical withdrawal thresholds and thermal withdrawal latencies were reduced after CCI and did not normalize after single or serial injections, nor with application of MDL-28170 via osmotic pumps. Although the calpain inhibitor MDL-28170 inhibits the early local cytokine upregulation in the sciatic nerve after CCI, pain behavior is not altered. This finding implies that local cytokine upregulation after nerve injury alone is only one factor in the induction and maintenance of neuropathic pain.<\/jats:p>","DOI":"10.3390\/molecules15053038","type":"journal-article","created":{"date-parts":[[2010,4,27]],"date-time":"2010-04-27T11:18:19Z","timestamp":1272367099000},"page":"3038-3047","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["MDL-28170 Has No Analgesic Effect on CCI Induced Neuropathic Pain in Mice"],"prefix":"10.3390","volume":"15","author":[{"given":"Nurcan","family":"\u00dc\u00e7eyler","sequence":"first","affiliation":[{"name":"Department of Neurology, University of W\u00fcrzburg, Josef-Schneider-Str. 11, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Biko","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of W\u00fcrzburg, Josef-Schneider-Str. 11, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Sommer","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of W\u00fcrzburg, Josef-Schneider-Str. 11, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2010,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.bbi.2006.10.003","article-title":"Early cytokine expression in mouse sciatic nerve after chronic constriction nerve injury depends on calpain","volume":"21","author":"Tscharke","year":"2007","journal-title":"Brain Behav.Immun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/(SICI)1097-4547(19991001)58:1<167::AID-JNR16>3.0.CO;2-K","article-title":"Caspase and calpain substrates: roles in synaptic plasticity and cell death","volume":"58","author":"Chan","year":"1999","journal-title":"J. Neurosci. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13254","DOI":"10.1073\/pnas.202355799","article-title":"Calpain as an effector of the Gq signaling pathway for inhibition of Wnt\/beta -catenin-regulated cell proliferation","volume":"99","author":"Li","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"14162","DOI":"10.1074\/jbc.M212255200","article-title":"Cross-talk between calpain and caspaseproteolytic systems during neuronal apoptosis","volume":"278","author":"Neumar","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0014-5793(94)01075-7","article-title":"The calpain-calpastatin system is regulated differently during human neuroblastoma cell differentiation to Schwannian and neuronal cells","volume":"353","author":"Saito","year":"1994","journal-title":"FEBS Lett."},{"key":"ref_6","unstructured":"Dyck, P.J., and Thomas, P.K. (2005). Peripheral neuropathy, Elsevier Saunders."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.pain.2004.04.031","article-title":"The calpain inhibitor MDL 28170 prevents inflammation-induced neurofilament light chain breakdown in the spinal cord and reduces thermal hyperalgesia","volume":"110","author":"Kunz","year":"2004","journal-title":"Pain"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1093\/jnen\/59.7.599","article-title":"Pathogenesis of axonal degeneration: Parallels between Wallerian degeneration and vincristine neuropathy","volume":"59","author":"Wang","year":"2000","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.expneurol.2009.04.013","article-title":"Mitochondrial micro-calpain is not involved in the processing of apoptosis-inducing factor","volume":"218","author":"Joshi","year":"2009","journal-title":"Exp. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.brainresbull.2008.11.002","article-title":"Participation of mu-calpain in status epilepticus-induced hippocampal injury","volume":"78","author":"Niquet","year":"2009","journal-title":"Brain Res. Bull."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1002\/jnr.21953","article-title":"Calpain-mediated degradation of G-substrate plays a critical role in retinal excitotoxicity for amacrine cells","volume":"87","author":"Nakazawa","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1089\/neu.2006.0224","article-title":"Calpain inhibitor MDL-28170 reduces the functional and structural deterioration of corpus callosum following fluid percussion injury","volume":"24","author":"Ai","year":"2007","journal-title":"J. Neurotrauma."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1089\/neu.2005.22.398","article-title":"Calpain inhibitors prevent neuronal cell death and ameliorate motor disturbances after compression-induced spinal cord injury in rats","volume":"22","author":"Arataki","year":"2005","journal-title":"J. Neurotrauma."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1089\/089771503321532842","article-title":"Preinjury administration of the calpain inhibitor MDL-28170 attenuates traumatically induced axonal injury","volume":"20","author":"Buki","year":"2003","journal-title":"J. Neurotrauma."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.brainres.2004.12.050","article-title":"Calpain inhibitor MDL 28170 protects hypoxic-ischemic brain injury in neonatal rats by inhibition of both apoptosis and necrosis","volume":"1037","author":"Kawamura","year":"2005","journal-title":"Brain Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1007\/s11064-007-9347-4","article-title":"Sustained calpain inhibition improves locomotor function and tissue sparing following contusive spinal cord injury","volume":"32","author":"Yu","year":"2007","journal-title":"Neurochem. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.neulet.2008.03.037","article-title":"Early cytokine gene expression in mouse CNS after peripheral nerve lesion","volume":"436","author":"Tscharke","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4081","DOI":"10.1523\/JNEUROSCI.23-10-04081.2003","article-title":"Inhibition of calpains prevents neuronal and behavioral deficits in an MPTP mouse model of Parkinson's disease","volume":"23","author":"Crocker","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/hep.21508","article-title":"Cardiotrophin-1 is an essential factor in the natural defense of the liver against apoptosis","volume":"45","author":"Marques","year":"2007","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/BF02256121","article-title":"Protective effect of MDL28170 against thioacetamide-induced acute liver failure in mice","volume":"11","author":"Wang","year":"2004","journal-title":"J. Biomed. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0304-3940(98)00266-3","article-title":"Postischemic treatment with calpain inhibitor MDL 28170 ameliorates brain damage in a gerbil model of global ischemia","volume":"247","author":"Li","year":"1998","journal-title":"Neurosci. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.brainresbull.2007.12.006","article-title":"Mu-calpain mediates hippocampal neuron death in rats after lithium-pilocarpine-induced status epilepticus","volume":"76","author":"Wang","year":"2008","journal-title":"Brain Res. Bull."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0304-3959(88)90209-6","article-title":"A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man","volume":"33","author":"Bennett","year":"1988","journal-title":"Pain"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/S0006-8993(97)01327-9","article-title":"Painful mononeuropathy in C57BL\/Wld mice with delayed wallerian degeneration: differential effects of cytokine production and nerve regeneration on thermal and mechanical hypersensitivity","volume":"784","author":"Sommer","year":"1998","journal-title":"Brain Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0165-0270(94)90144-9","article-title":"Quantitative assessment of tactile allodynia in the rat paw","volume":"53","author":"Chaplan","year":"1994","journal-title":"J. Neurosci. Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0304-3959(88)90026-7","article-title":"A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia","volume":"32","author":"Hargreaves","year":"1988","journal-title":"Pain"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/15\/5\/3038\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T22:02:16Z","timestamp":1760220136000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/15\/5\/3038"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4,27]]},"references-count":26,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2010,5]]}},"alternative-id":["15053038"],"URL":"https:\/\/doi.org\/10.3390\/molecules15053038","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,4,27]]}}}