{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:23:29Z","timestamp":1786123409670,"version":"build-2736575974"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,5]]},"DOI":"10.1213\/ane.0b013e318168514b","type":"journal-article","created":{"date-parts":[[2008,4,16]],"date-time":"2008-04-16T03:04:05Z","timestamp":1208315045000},"page":"1456-1464","source":"Crossref","is-referenced-by-count":65,"title":["In Vitro, Inhibition of Mitogen-Activated Protein Kinase Pathways Protects Against Bupivacaine- and Ropivacaine-Induced Neurotoxicity"],"prefix":"10.1213","volume":"106","author":[{"given":"Philipp","family":"Lirk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Haller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Peter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leopold","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Tomaselli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Klimaschewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Gerner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-22-20210902","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1097\/00000542-199606000-00012","article-title":"Prospective study of the incidence of transient radicular irritation in patients undergoing spinal anesthesia.","volume":"84","author":"Pollock","year":"1996","journal-title":"Anesthesiology"},{"key":"R2-22-20210902","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1097\/00000542-199709000-00005","article-title":"Serious complications related to regional anesthesia: results of a prospective survey in France.","volume":"87","author":"Auroy","year":"1997","journal-title":"Anesthesiology"},{"key":"R3-22-20210902","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1097\/00000542-200211000-00034","article-title":"Major complications of regional anesthesia in France: The SOS Regional Anesthesia Hotline Service.","volume":"97","author":"Auroy","year":"2002","journal-title":"Anesthesiology"},{"key":"R4-22-20210902","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1213\/00000539-200202000-00016","article-title":"The neurotoxicity of local anesthetics on growing neurons: a comparative study of lidocaine, bupivacaine, mepivacaine, and ropivacaine.","volume":"94","author":"Radwan","year":"2002","journal-title":"Anesth Analg"},{"key":"R5-22-20210902","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1097\/00000542-200208000-00021","article-title":"Intrathecal ropivacaine in rabbits: pharmacodynamic and neurotoxicologic study.","volume":"97","author":"Malinovsky","year":"2002","journal-title":"Anesthesiology"},{"key":"R6-22-20210902","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1213\/01.ANE.0000155960.61157.12","article-title":"The comparative neurotoxicity of intrathecal lidocaine and bupivacaine in rats.","volume":"101","author":"Sakura","year":"2005","journal-title":"Anesth Analg"},{"key":"R7-22-20210902","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1097\/00000542-200112000-00040","article-title":"Ropivacaine neurotoxicity: a stab in the back?","volume":"95","author":"de Jong","year":"2001","journal-title":"Anesthesiology"},{"key":"R8-22-20210902","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.jclinane.2003.07.012","article-title":"Toxic effects of epidural analgesia with ropivacaine 0.2% in a diabetic patient.","volume":"16","author":"Al-Nasser","year":"2004","journal-title":"J Clin Anesth"},{"key":"R9-22-20210902","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1097\/00000542-200606000-00023","article-title":"Mitigation of direct neurotoxic effects of lidocaine and amitriptyline by inhibition of p38 mitogen-activated protein kinase in vitro and in vivo.","volume":"104","author":"Lirk","year":"2006","journal-title":"Anesthesiology"},{"key":"R10-22-20210902","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1097\/00000542-200611000-00025","article-title":"Neurotoxicity of Lidocaine Involves Specific Activation of the p38 Mitogen-activated Protein Kinase, but Not Extracellular Signal-regulated or c-jun N-Terminal Kinases, and Is Mediated by Arachidonic Acid Metabolites.","volume":"105","author":"Haller","year":"2006","journal-title":"Anesthesiology"},{"key":"R11-22-20210902","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1097\/00000542-200205000-00024","article-title":"Involvement of the mitogen-activated protein kinase family in tetracaine-induced PC12 cell death.","volume":"96","author":"Tan","year":"2002","journal-title":"Anesthesiology"},{"key":"R12-22-20210902","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1213\/01.ANE.0000047201.85815.9D","article-title":"The induction of apoptosis by local anesthetics: a comparison between lidocaine and ropivacaine.","volume":"96","author":"Boselli","year":"2003","journal-title":"Anesth Analg"},{"key":"R13-22-20210902","doi-asserted-by":"crossref","first-page":"77","DOI":"10.2131\/jts.28.77","article-title":"Biochemical and microarray analyses of bupivacaine-induced apoptosis.","volume":"28","author":"Unami","year":"2003","journal-title":"J Toxicol Sci"},{"key":"R14-22-20210902","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0169-328X(03)00279-1","article-title":"L-type calcium channel activation up-regulates the mRNAs for two different sodium channel alpha subunits (Nav1.2 and Nav1.3) in rat pituitary GH3 cells.","volume":"116","author":"Vega","year":"2003","journal-title":"Brain Res Mol Brain Res"},{"key":"R15-22-20210902","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/BF00656997","article-title":"Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.","volume":"391","author":"Hamill","year":"1981","journal-title":"Pflugers Arch"},{"key":"R16-22-20210902","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1085\/jgp.94.2.213","article-title":"Sodium channel gating in clonal pituitary cells. The inactivation step is not voltage dependent.","volume":"94","author":"Cota","year":"1989","journal-title":"J Gen Physiol"},{"key":"R17-22-20210902","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1213\/01.ane.0000216018.62549.bb","article-title":"The neurotoxic effects of amitriptyline are mediated by apoptosis and are effectively blocked by inhibition of caspase activity.","volume":"102","author":"Lirk","year":"2006","journal-title":"Anesth Analg"},{"key":"R18-22-20210902","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/00008506-200401000-00017","article-title":"Neurotoxicity of lidocaine: implications for spinal anesthesia and neuroprotection.","volume":"16","author":"Johnson","year":"2004","journal-title":"J Neurosurg Anesthesiol"},{"key":"R19-22-20210902","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S1098-7339(97)80032-6","article-title":"Two cases of cauda equina syndrome following spinal-epidural anesthesia.","volume":"22","author":"Kubina","year":"1997","journal-title":"Reg Anesth"},{"key":"R20-22-20210902","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1213\/01.ANE.0000184126.57327.C3","article-title":"Persistent cauda equina syndrome with no identifiable facilitating condition after an uneventful single spinal administration of 0.5% hyperbaric bupivacaine.","volume":"101","author":"Chabbouh","year":"2005","journal-title":"Anesth Analg"},{"key":"R21-22-20210902","first-page":"338","article-title":"Local anesthetic neurotoxicity does not result from blockade of voltage-gated sodium channels.","volume":"81","author":"Sakura","year":"1995","journal-title":"Anesth Analg"},{"key":"R22-22-20210902","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1213\/01.ANE.0000068885.78816.5B","article-title":"A comparison of the neurotoxic effects on the spinal cord of tetracaine, lidocaine, bupivacaine, and ropivacaine administered intrathecally in rabbits.","volume":"97","author":"Yamashita","year":"2003","journal-title":"Anesth Analg"},{"key":"R23-22-20210902","first-page":"1213","article-title":"Characteristics of ropivacaine block of Na+ channels in rat dorsal root ganglion neurons.","volume":"91","author":"Oda","year":"2000","journal-title":"Anesth Analg"},{"key":"R24-22-20210902","first-page":"885","article-title":"Fundamental properties of local anesthetics: half-maximal blocking concentrations for tonic block of Na+ and K+ channels in peripheral nerve.","volume":"87","author":"Brau","year":"1998","journal-title":"Anesth Analg"},{"key":"R25-22-20210902","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1046\/j.1365-2346.1998.00218.x","article-title":"Local anaesthetic effects on tetrodotoxin-resistant Na+ currents in rat dorsal root ganglion neurones.","volume":"15","author":"Brau","year":"1998","journal-title":"Eur J Anaesthesiol"},{"key":"R26-22-20210902","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1097\/00000542-199801000-00025","article-title":"Blockade of Na+ and K+ currents by local anesthetics in the dorsal horn neurons of the spinal cord.","volume":"88","author":"Olschewski","year":"1998","journal-title":"Anesthesiology"},{"key":"R27-22-20210902","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/nrd1177","article-title":"p38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases.","volume":"2","author":"Kumar","year":"2003","journal-title":"Nat Rev Drug Discov"},{"key":"R28-22-20210902","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1111\/j.1471-4159.2004.02996.x","article-title":"Spinal p38beta isoform mediates tissue injury-induced hyperalgesia and spinal sensitization.","volume":"92","author":"Svensson","year":"2005","journal-title":"J Neurochem"},{"key":"R29-22-20210902","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s00401-004-0896-1","article-title":"The perineurium modifies the effects of phenol and glycerol in rat sciatic nerve.","volume":"108","author":"Westerlund","year":"2004","journal-title":"Acta Neuropathol (Berl)"},{"key":"R30-22-20210902","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0022-3565(24)37483-X","article-title":"Lidocaine toxicity in primary afferent neurons from the rat.","volume":"285","author":"Gold","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"R31-22-20210902","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1097\/00000542-200406000-00026","article-title":"Amitriptyline neurotoxicity: dose-related pathology after topical application to rat sciatic nerve.","volume":"100","author":"Estebe","year":"2004","journal-title":"Anesthesiology"},{"key":"R32-22-20210902","first-page":"344","article-title":"Differential block of n-propyl derivatives of amitriptyline and doxepin for sciatic nerve block in rats.","volume":"30","author":"Gerner","year":"2005","journal-title":"Reg Anesth Pain Med"},{"key":"R33-22-20210902","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1046\/j.1365-2443.2002.00591.x","article-title":"Neuronal p38 MAPK signalling: an emerging regulator of cell fate and function in the nervous system.","volume":"7","author":"Takeda","year":"2002","journal-title":"Genes Cells"},{"key":"R34-22-20210902","doi-asserted-by":"crossref","first-page":"18986","DOI":"10.1074\/jbc.M108084200","article-title":"Enhancement of hyperthermia-induced apoptosis by local anesthetics on human histiocytic lymphoma U937 cells.","volume":"277","author":"Arai","year":"2002","journal-title":"J Biol Chem"},{"key":"R35-22-20210902","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1097\/00000542-200411000-00019","article-title":"Mitochondrial injury and caspase activation by the local anesthetic lidocaine.","volume":"101","author":"Johnson","year":"2004","journal-title":"Anesthesiology"},{"key":"R36-22-20210902","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.2337\/diabetes.53.7.1851","article-title":"Mitogen-activated protein kinase p38 mediates reduced nerve conduction velocity in experimental diabetic neuropathy: interactions with aldose reductase.","volume":"53","author":"Price","year":"2004","journal-title":"Diabetes"},{"key":"R37-22-20210902","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1213\/01.ane.0000243384.75713.df","article-title":"Neurologic complications after neuraxial anesthesia or analgesia in patients with preexisting peripheral sensorimotor neuropathy or diabetic polyneuropathy.","volume":"103","author":"Hebl","year":"2006","journal-title":"Anesth Analg"},{"key":"R38-22-20210902","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1097\/00000542-199211000-00017","article-title":"Local anesthetic-induced conduction block and nerve fiber injury in streptozotocin-diabetic rats.","volume":"77","author":"Kalichman","year":"1992","journal-title":"Anesthesiology"}],"container-title":["Anesthesia & Analgesia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1213\/ane.0b013e318168514b","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:27:43Z","timestamp":1786112863000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00000539-200805000-00022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,5]]},"references-count":38,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2008]]}},"URL":"https:\/\/doi.org\/10.1213\/ane.0b013e318168514b","relation":{},"ISSN":["0003-2999"],"issn-type":[{"value":"0003-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2008,5]]}}}