{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:44:09Z","timestamp":1791193449613,"version":"4.1.0"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,11]]},"DOI":"10.1016\/j.pain.2011.07.025","type":"journal-article","created":{"date-parts":[[2011,9,14]],"date-time":"2011-09-14T00:28:31Z","timestamp":1315960111000},"page":"2582-2595","source":"Crossref","is-referenced-by-count":94,"title":["Systemic inhibition of the mammalian target of rapamycin (mTOR) pathway reduces neuropathic pain in mice"],"prefix":"10.1097","volume":"152","author":[{"given":"Ilona","family":"Obara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keri K.","family":"Tochiki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine M.","family":"G\u00e9ranton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona B.","family":"Carr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget M.","family":"Lumb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingsong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Hunt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R5-21-20210112","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1126\/science.1156916","article-title":"The cell and molecular basis of mechanical, cold, and inflammatory pain.","volume":"321","author":"Abrahamsen","year":"2008","journal-title":"Science"},{"key":"R10-21-20210112","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1016\/j.transproceed.2009.06.083","article-title":"Efficacy, tolerance, and safety of mammalian target of rapamycin inhibitors as rescue immunosuppressants in liver transplantation.","volume":"41","author":"Alamo","year":"2009","journal-title":"Transplant Proc"},{"key":"R15-21-20210112","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1016\/j.jpain.2010.03.013","article-title":"Mammalian target of rapamycin signaling in the spinal cord is required for neuronal plasticity and behavioral hypersensitivity associated with neuropathy in the rat.","volume":"11","author":"Asante","year":"2010","journal-title":"J Pain"},{"key":"R20-21-20210112","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1634\/theoncologist.2009-S502","article-title":"Future directions in neuropathic pain therapy: closing the translational loop.","volume":"15","author":"Backonja","year":"2010","journal-title":"Oncologist"},{"key":"R25-21-20210112","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/S1474-4422(10)70143-5","article-title":"Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment.","volume":"9","author":"Baron","year":"2010","journal-title":"Lancet Neurol"},{"key":"R30-21-20210112","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.pain.2005.10.036","article-title":"Assessment and analysis of mechanical allodynia-like behavior induced by spared nerve injury (SNI) in the mouse.","volume":"122","author":"Bourquin","year":"2006","journal-title":"Pain"},{"key":"R35-21-20210112","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ejpain.2005.06.009","article-title":"Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment.","volume":"10","author":"Breivik","year":"2006","journal-title":"Eur J Pain"},{"key":"R40-21-20210112","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1016\/j.pain.2010.11.005","article-title":"Pathophysiology of postoperative pain.","volume":"152","author":"Brennan","year":"2011","journal-title":"Pain"},{"key":"R45-21-20210112","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/0304-3959(94)90023-X","article-title":"Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain.","volume":"59","author":"Choi","year":"1994","journal-title":"Pain"},{"key":"R50-21-20210112","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/0304-3940(94)11154-B","article-title":"Role of peri-axonal inflammation in the development of thermal hyperalgesia and guarding behavior in a rat model of neuropathic pain.","volume":"184","author":"Clatworthy","year":"1995","journal-title":"Neurosci Lett"},{"key":"R55-21-20210112","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1523\/JNEUROSCI.4103-08.2009","article-title":"The Rheb-mTOR pathway is upregulated in reactive astrocytes of the injured spinal cord.","volume":"29","author":"Codeluppi","year":"2009","journal-title":"J Neurosci"},{"key":"R60-21-20210112","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.neuron.2008.10.055","article-title":"Translational control of long-lasting synaptic plasticity and memory.","volume":"61","author":"Costa-Mattioli","year":"2009","journal-title":"Neuron"},{"key":"R65-21-20210112","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/0306-4522(93)90127-2","article-title":"Altered expression of nerve growth factor in the skin of transgenic mice leads to changes in response to mechanical stimuli.","volume":"56","author":"Davis","year":"1993","journal-title":"Neuroscience"},{"key":"R70-21-20210112","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0304-3959(00)00276-1","article-title":"Spared nerve injury: an animal model of persistent peripheral neuropathic pain.","volume":"87","author":"Decosterd","year":"2000","journal-title":"Pain"},{"key":"R75-21-20210112","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1016\/j.bcp.2009.06.097","article-title":"Involvement of mTOR kinase in cytokine-dependent microglial activation and cell proliferation.","volume":"78","author":"Dello","year":"2009","journal-title":"Biochem Pharmacol"},{"key":"R80-21-20210112","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.brainresrev.2004.07.015","article-title":"Abeta-fiber nociceptive primary afferent neurons: a review of incidence and properties in relation to other afferent A-fiber neurons in mammals.","volume":"46","author":"Djouhri","year":"2004","journal-title":"Brain Res Brain Res Rev"},{"key":"R85-21-20210112","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.4065\/mcp.2009.0649","article-title":"Recommendations for the pharmacological management of neuropathic pain: an overview and literature update.","volume":"85","author":"Dworkin","year":"2010","journal-title":"Mayo Clin Proc"},{"key":"R90-21-20210112","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1517\/13543784.2011.541154","article-title":"Current and future directions in mammalian target of rapamycin inhibitors development.","volume":"20","author":"Fasolo","year":"2011","journal-title":"Expert Opin Investig Drugs"},{"key":"R95-21-20210112","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1371\/journal.pbio.1000038","article-title":"Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2.","volume":"7","author":"Feldman","year":"2009","journal-title":"PLoS Biol"},{"key":"R100-21-20210112","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/0006-8993(90)90618-L","article-title":"Neuronal intermediate filaments in rat dorsal root ganglia: differential distribution of peripherin and neurofilament protein immunoreactivity and effect of capsaicin.","volume":"515","author":"Ferri","year":"1990","journal-title":"Brain Res"},{"key":"R105-21-20210112","doi-asserted-by":"crossref","first-page":"15017","DOI":"10.1523\/JNEUROSCI.3451-09.2009","article-title":"A rapamycin-sensitive signaling pathway is essential for the full expression of persistent pain states.","volume":"29","author":"Geranton","year":"2009","journal-title":"J Neurosci"},{"key":"R110-21-20210112","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/978-3-662-09889-9_6","article-title":"Control of translation by the target of rapamycin proteins.","volume":"27","author":"Gingras","year":"2001","journal-title":"Prog Mol Subcell Biol"},{"key":"R115-21-20210112","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/nm.2235","article-title":"Nociceptor sensitization in pain pathogenesis.","volume":"16","author":"Gold","year":"2010","journal-title":"Nat Med"},{"key":"R120-21-20210112","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/S0896-6273(03)00770-0","article-title":"Axoplasmic importins enable retrograde injury signaling in lesioned nerve.","volume":"40","author":"Hanz","year":"2003","journal-title":"Neuron"},{"key":"R125-21-20210112","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"},{"key":"R130-21-20210112","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1101\/gad.1212704","article-title":"Upstream and downstream of mTOR.","volume":"18","author":"Hay","year":"2004","journal-title":"Genes Dev"},{"key":"R135-21-20210112","doi-asserted-by":"crossref","first-page":"6352","DOI":"10.1523\/JNEUROSCI.0995-04.2004","article-title":"Activation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway is required for metabotropic glutamate receptor-dependent long-term depression.","volume":"24","author":"Hou","year":"2004","journal-title":"J Neurosci"},{"key":"R140-21-20210112","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1002\/glia.20871","article-title":"Microglia and neuropathic pain.","volume":"57","author":"Inoue","year":"2009","journal-title":"Glia"},{"key":"R145-21-20210112","doi-asserted-by":"crossref","first-page":"e1961","DOI":"10.1371\/journal.pone.0001961","article-title":"Local translation in primary afferent fibers regulates nociception.","volume":"3","author":"Jimenez-Diaz","year":"2008","journal-title":"PLoS ONE"},{"key":"R150-21-20210112","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.pain.2009.02.006","article-title":"Profiling of dynamically changed gene expression in dorsal root ganglia post peripheral nerve injury and a critical role of injury-induced glial fibrillary acetic protein in maintenance of pain behaviors.","volume":"143","author":"Kim","year":"2009","journal-title":"Pain"},{"key":"R155-21-20210112","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/nrn1557","article-title":"Biochemical mechanisms for translational regulation in synaptic plasticity.","volume":"5","author":"Klann","year":"2004","journal-title":"Nat Rev Neurosci"},{"key":"R160-21-20210112","doi-asserted-by":"crossref","first-page":"12923","DOI":"10.1073\/pnas.2132711100","article-title":"MTor is required for hypertrophy of Pten-deficient neuronal soma in vivo.","volume":"100","author":"Kwon","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"R165-21-20210112","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.1242\/jcs.051011","article-title":"MTOR signaling at a glance.","volume":"122","author":"Laplante","year":"2009","journal-title":"J Cell Sci"},{"key":"R170-21-20210112","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1038\/sj.bjc.6604636","article-title":"MTORC1 inhibitors: is temsirolimus in renal cancer telling us how they really work?","volume":"99","author":"Le","year":"2008","journal-title":"Br J Cancer"},{"key":"R175-21-20210112","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1002\/gcc.20357","article-title":"Combination of a rapamycin analog (CCI-779) and interferon-gamma is more effective than single agents in treating a mouse model of tuberous sclerosis complex.","volume":"45","author":"Lee","year":"2006","journal-title":"Genes Chromosomes Cancer"},{"key":"R180-21-20210112","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/gcc.20118","article-title":"Efficacy of a rapamycin analog (CCI-779) and IFN-gamma in tuberous sclerosis mouse models.","volume":"42","author":"Lee","year":"2005","journal-title":"Genes Chromosomes Cancer"},{"key":"R185-21-20210112","doi-asserted-by":"crossref","first-page":"7146","DOI":"10.1021\/jm101144f","article-title":"Discovery of 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3- yl)benzoh1,6naphthyridin-2(1H)-one as a highly potent, selective mammalian target of rapamycin (mTOR) inhibitor for the treatment of cancer.","volume":"53","author":"Liu","year":"2010","journal-title":"J Med Chem"},{"key":"R190-21-20210112","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/nature05662","article-title":"Mechanisms of sensory transduction in the skin.","volume":"445","author":"Lumpkin","year":"2007","journal-title":"Nature"},{"key":"R195-21-20210112","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s00005-010-0106-x","article-title":"Dual peripheral actions of immune cells in neuropathic pain.","volume":"59","author":"Machelska","year":"2011","journal-title":"Arch Immunol Ther Exp (Warsz)"},{"key":"R200-21-20210112","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/brain\/124.9.1754","article-title":"Roles of capsaicin-insensitive nociceptors in cutaneous pain and secondary hyperalgesia.","volume":"124","author":"Magerl","year":"2001","journal-title":"Brain"},{"key":"R205-21-20210112","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ejphar.2009.09.030","article-title":"Differential activation of spinal microglial and astroglial cells in a mouse model of peripheral neuropathic pain.","volume":"623","author":"Mika","year":"2009","journal-title":"Eur J Pharmacol"},{"key":"R210-21-20210112","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1096\/fj.06-6155com","article-title":"RNAi pathway is functional in peripheral nerve axons.","volume":"21","author":"Murashov","year":"2007","journal-title":"FASEB J"},{"key":"R215-21-20210112","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1016\/j.neuroscience.2010.05.067","article-title":"Mammalian target of rapamycin in spinal cord neurons mediates hypersensitivity induced by peripheral inflammation.","volume":"169","author":"Norsted","year":"2010","journal-title":"Neuroscience"},{"key":"R220-21-20210112","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1158\/0008-5472.CAN-05-2925","article-title":"MTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt.","volume":"66","author":"OReilly","year":"2006","journal-title":"Cancer Res"},{"key":"R225-21-20210112","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.neulet.2010.06.039","article-title":"Antihyperalgesic and antiallodynic effect of sirolimus in neuropathic pain and the role of cytokines in this effect.","volume":"481","author":"Orhan","year":"2010","journal-title":"Neurosci Lett"},{"key":"R230-21-20210112","doi-asserted-by":"crossref","first-page":"13958","DOI":"10.1523\/JNEUROSCI.4383-07.2007","article-title":"Decreased nociceptive sensitization in mice lacking the fragile X mental retardation protein: role of mGluR15 and mTOR.","volume":"27","author":"Price","year":"2007","journal-title":"J Neurosci"},{"key":"R235-21-20210112","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1126\/science.1131693","article-title":"Activity- and mTOR-dependent suppression of Kv1.1 channel mRNA translation in dendrites.","volume":"314","author":"Raab-Graham","year":"2006","journal-title":"Science"},{"key":"R240-21-20210112","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/ng1362","article-title":"Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease.","volume":"36","author":"Ravikumar","year":"2004","journal-title":"Nat Genet"},{"key":"R245-21-20210112","doi-asserted-by":"crossref","first-page":"20104","DOI":"10.1074\/jbc.M201745200","article-title":"Regulation of an activated S6 kinase 1 variant reveals a novel mammalian target of rapamycin phosphorylation site.","volume":"277","author":"Saitoh","year":"2002","journal-title":"J Biol Chem"},{"key":"R250-21-20210112","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/S0006-8993(00)02596-8","article-title":"Carrageenan-induced thermal hyperalgesia in the mouse: role of nerve growth factor and the mitogen-activated protein kinase pathway.","volume":"876","author":"Sammons","year":"2000","journal-title":"Brain Res"},{"key":"R255-21-20210112","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00221-009-1809-2","article-title":"Translating nociceptive processing into human pain models.","volume":"196","author":"Schmelz","year":"2009","journal-title":"Exp Brain Res"},{"key":"R260-21-20210112","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0092-8674(00)00117-3","article-title":"TOR, a central controller of cell growth.","volume":"103","author":"Schmelzle","year":"2000","journal-title":"Cell"},{"key":"R265-21-20210112","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/nature08505","article-title":"Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors.","volume":"462","author":"Seal","year":"2009","journal-title":"Nature"},{"key":"R270-21-20210112","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/S0009-9120(98)00045-9","article-title":"Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression.","volume":"31","author":"Sehgal","year":"1998","journal-title":"Clin Biochem"},{"key":"R275-21-20210112","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/S0306-4522(03)00362-2","article-title":"Intact carrageenan-induced thermal hyperalgesia in mice lacking inducible nitric oxide synthase.","volume":"120","author":"Tao","year":"2003","journal-title":"Neuroscience"},{"key":"R280-21-20210112","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/nri2546","article-title":"Immunoregulatory functions of mTOR inhibition.","volume":"9","author":"Thomson","year":"2009","journal-title":"Nat Rev Immunol"},{"key":"R285-21-20210112","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/nrn2947","article-title":"Neuronal circuitry for pain processing in the dorsal horn.","volume":"11","author":"Todd","year":"2010","journal-title":"Nat Rev Neurosci"},{"key":"R290-21-20210112","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0079-6123(00)29025-0","article-title":"Multiple mechanisms of secondary hyperalgesia.","volume":"129","author":"Treede","year":"2000","journal-title":"Prog Brain Res"},{"key":"R295-21-20210112","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1523\/JNEUROSCI.3073-04.2005","article-title":"Axonal protein synthesis and degradation are necessary for efficient growth cone regeneration.","volume":"25","author":"Verma","year":"2005","journal-title":"J Neurosci"},{"key":"R300-21-20210112","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1038\/sj.onc.1209990","article-title":"Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism.","volume":"26","author":"Wan","year":"2007","journal-title":"Oncogene"},{"key":"R305-21-20210112","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1523\/JNEUROSCI.4235-04.2005","article-title":"Differential transport and local translation of cytoskeletal, injury-response, and neurodegeneration protein mRNAs in axons.","volume":"25","author":"Willis","year":"2005","journal-title":"J Neurosci"},{"key":"R310-21-20210112","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1523\/JNEUROSCI.2139-10.2011","article-title":"Spinal phosphinositide 3-kinase-Akt-mammalian target of rapamycin signaling cascades in inflammation-induced hyperalgesia.","volume":"31","author":"Xu","year":"2011","journal-title":"J Neurosci"},{"key":"R315-21-20210112","doi-asserted-by":"crossref","first-page":"9291","DOI":"10.1523\/JNEUROSCI.21-23-09291.2001","article-title":"A functional role for intra-axonal protein synthesis during axonal regeneration from adult sensory neurons.","volume":"21","author":"Zheng","year":"2001","journal-title":"J Neurosci"}],"container-title":["Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1016\/j.pain.2011.07.025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T20:16:36Z","timestamp":1786047396000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00006396-201111000-00021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11]]},"references-count":63,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2011]]}},"URL":"https:\/\/doi.org\/10.1016\/j.pain.2011.07.025","relation":{},"ISSN":["0304-3959"],"issn-type":[{"value":"0304-3959","type":"print"}],"subject":[],"published":{"date-parts":[[2011,11]]}}}