{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T02:58:41Z","timestamp":1784257121474,"version":"3.55.0"},"reference-count":64,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,9,26]],"date-time":"2017-09-26T00:00:00Z","timestamp":1506384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Approximately 40% of patients with chronic low back pain have a neuropathic component. In this study, we assessed the effects of analgesics on tactile hypersensitivity and walking distance in the rat <jats:italic>cauda equina<\/jats:italic> compression (<jats:styled-content style=\"fixed-case\">CEC<\/jats:styled-content>) model of neuropathic low back pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The effects of analgesics on tactile hypersensitivity were examined using the von Frey test in <jats:styled-content style=\"fixed-case\">CEC<\/jats:styled-content> and partial sciatic nerve ligation (<jats:styled-content style=\"fixed-case\">pSNL<\/jats:styled-content>) models. Effects on walking distance were assessed using a treadmill test. Levels of \u03b12\u03b41 subunit and <jats:styled-content style=\"fixed-case\">ATF<\/jats:styled-content>\u20103 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> in dorsal\u2010root ganglion (<jats:styled-content style=\"fixed-case\">DRG<\/jats:styled-content>) neurons and those of \u03b12\u03b41 subunit protein in the spinal cord were determined using quantitative <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and western blotting, respectively. Histological features were assessed using immunohistological methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Histological changes indicating nerve damage (increase in <jats:styled-content style=\"fixed-case\">ATF<\/jats:styled-content>\u20103 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>, decrease in <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010200 and an increase in <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>68 immunoreactivity) were observed in the <jats:styled-content style=\"fixed-case\">CEC<\/jats:styled-content> model. Duloxetine had analgesic effects in both models and improved walking distance in the <jats:styled-content style=\"fixed-case\">CEC<\/jats:styled-content> model. Pregabalin had analgesic effects in both models; however, the effect was weaker in the <jats:styled-content style=\"fixed-case\">CEC<\/jats:styled-content> model than in the <jats:styled-content style=\"fixed-case\">pSNL<\/jats:styled-content> model. \u03b12\u03b41 subunit expression in <jats:styled-content style=\"fixed-case\">DRG<\/jats:styled-content> neurons and in the spinal cord was unchanged in the <jats:styled-content style=\"fixed-case\">CEC<\/jats:styled-content> model, but significantly increased in the <jats:styled-content style=\"fixed-case\">pSNL<\/jats:styled-content> model. Indomethacin had no analgesic effect in either model. Intrathecal yohimbine inhibited the effects of duloxetine with significant effects on depression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest that the analgesic effects of duloxetine are mainly mediated by the spinal monoamine system, independent of the antidepressant effects of this agent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>The findings of this study suggest that duloxetine may be an effective treatment of broad neuropathic pain states, including neuropathic low back pain. The analgesic effects of duloxetine might be mediated by alterations of the descending pain modulatory pathways in the spinal cord, independent of the antidepressant effects.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1125","type":"journal-article","created":{"date-parts":[[2017,9,27]],"date-time":"2017-09-27T01:18:58Z","timestamp":1506475138000},"page":"355-369","source":"Crossref","is-referenced-by-count":18,"title":["Effects of duloxetine on pain and walking distance in neuropathic pain models via modulation of the spinal monoamine system"],"prefix":"10.1002","volume":"22","author":[{"given":"K.","family":"Minami","sequence":"first","affiliation":[{"name":"Pain &amp; Neuroscience, Drug Discovery &amp; Disease Research Laboratory Shionogi &amp; Co., Ltd. Toyonaka Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Tamano","sequence":"additional","affiliation":[{"name":"Pain &amp; Neuroscience, Drug Discovery &amp; Disease Research Laboratory Shionogi &amp; Co., Ltd. Toyonaka Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Kasai","sequence":"additional","affiliation":[{"name":"Pain &amp; Neuroscience, Drug Discovery &amp; Disease Research Laboratory Shionogi &amp; Co., Ltd. Toyonaka Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Oyama","sequence":"additional","affiliation":[{"name":"Pain &amp; Neuroscience, Drug Discovery &amp; Disease Research Laboratory Shionogi &amp; Co., Ltd. Toyonaka Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Pain &amp; Neuroscience, Drug Discovery &amp; Disease Research Laboratory Shionogi &amp; Co., Ltd. Toyonaka Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Shinohara","sequence":"additional","affiliation":[{"name":"Pain &amp; Neuroscience, Drug Discovery &amp; Disease Research Laboratory Shionogi &amp; Co., Ltd. Toyonaka Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Asaki","sequence":"additional","affiliation":[{"name":"Pain &amp; Neuroscience, Drug Discovery &amp; Disease Research Laboratory Shionogi &amp; Co., Ltd. Toyonaka Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)01312-4"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0154114"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/PSY.0b013e318185c510"},{"key":"e_1_2_7_5_1","first-page":"CD011681","article-title":"Selective serotonin reuptake inhibitors (SSRIs) and serotonin\u2010norepinephrine reuptake inhibitors (SNRIs) for the prevention of tension\u2010type headache in adults","volume":"5","author":"Banzi R.","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejp.838"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2011.02.033"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X13508508"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2016.1202764"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2014.06.018"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-199809010-00012"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(94)90144-9"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2009.06.024"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.5055\/jom.2008.0023"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-147-7-200710020-00006"},{"key":"e_1_2_7_16_1","volume-title":"Noninvasive Treatments for Low Back Pain","author":"Chou R.","year":"2016"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12955-014-0171-7"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3956(02)00060-2"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2001.116443"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.98B3.36036"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409066103"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.14.030191.001251"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/pme.12229"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-009-0032-y"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10357"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2005.03.029"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.04.043"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-199412150-00002"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2016.09.011"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.11.029"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-014-3723-y"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/AJP.0000000000000343"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2006.08.005"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(97)00049-3"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.25.3.396.61600"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000001707"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(98)00230-9"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.109728"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2982-04.2004"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-06-01868.2001"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128321"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0718-y"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000539-200206000-00030"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-3278(03)00109-1"},{"key":"e_1_2_7_45_1","first-page":"106","article-title":"Duloxetine for the treatment of major depressive disorder","volume":"36","author":"Nemeroff C.B.","year":"2002","journal-title":"Psychopharmacol Bull"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1213\/01.ANE.0000149546.97299.A2"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.4184\/asj.2016.10.3.516"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(92)90144-Z"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.060582"},{"key":"e_1_2_7_50_1","first-page":"99","article-title":"Duloxetine for the management of fibromyalgia syndrome","volume":"2","author":"Scholz B.A.","year":"2009","journal-title":"J Pain Res"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(90)91074-S"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.05.068"},{"key":"e_1_2_7_53_1","first-page":"753","article-title":"Opioid analgesia hard to tolerate and not effective for chronic low back pain","volume":"94","author":"Shaughnessy A.F.","year":"2016","journal-title":"Am Fam Physician"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2014.03.046"},{"key":"e_1_2_7_55_1","first-page":"487","article-title":"Effectiveness of pregabalin for the treatment of chronic low back pain with accompanying lower limb pain (neuropathic component): A non\u2010interventional study in Japan","volume":"8","author":"Taguchi T.","year":"2015","journal-title":"J Pain Res"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0270(00)00342-3"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2016.01.025"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-15-283"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2008.05.005"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1999.0814"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2010.12.003"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2007.0274"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1986.64.1.0064"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1097\/PHM.0b013e3182971321"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000240225.04000.1a"}],"container-title":["European Journal of Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fejp.1125","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejp.1125","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ejp.1125","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejp.1125","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T12:06:41Z","timestamp":1693310801000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ejp.1125"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,26]]},"references-count":64,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1002\/ejp.1125"],"URL":"https:\/\/doi.org\/10.1002\/ejp.1125","archive":["Portico"],"relation":{},"ISSN":["1090-3801","1532-2149"],"issn-type":[{"value":"1090-3801","type":"print"},{"value":"1532-2149","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,26]]}}}