{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T16:41:19Z","timestamp":1774802479995,"version":"3.50.1"},"reference-count":35,"publisher":"BMJ","issue":"6","funder":[{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2017,2,23]]},"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Osteoarthritis (OA) pain is a major cause of long-term disability and chronic pain in the adult population. One in five patients does not receive satisfactory pain relief, which reflects the complexity of chronic pain and the current lack of understanding of mechanisms of chronic pain. Recently, duloxetine has demonstrated clinically relevant pain relief, but only in half of treated patients with OA. Here, the aim is to investigate the neural mechanisms of pain relief and neural signatures that may predict treatment response to duloxetine in chronic knee OA pain.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>This is an ongoing single-centre randomised placebo-controlled mechanistic study (2:1 (placebo) allocation), using a multimodal neuroimaging approach, together with psychophysiological (quantitative sensory testing), genetics and questionnaire assessments. Eighty-one subjects with chronic knee OA pain are planned to power for between-group comparisons (placebo, duloxetine responder and duloxetine non-responder). Participants have a baseline assessment and, following 6\u2009weeks of duloxetine (30\u2009mg for 2\u2009weeks, then 60\u2009mg for 4\u2009weeks), a follow-up evaluation. Brain imaging is performed at 3T with blood-oxygen-level dependent functional MRI at rest and during pin-prick nociceptive stimulation for main outcome assessment; arterial spin labelling and structural imaging (T1-weighted) for secondary outcome assessment. Questionnaires evaluate pain, negative affect, quality of sleep and cognition.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>The study has been approved by the East Midlands, Nottingham and is being carried out under the principles of the Declaration of Helsinki (64th, 2013) and Good Clinical Practice standards. Results will be disseminated in peer-reviewed journals and at scientific conferences.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>This trial is registered at ClinicalTrials.gov (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02208778\">NCT02208778<\/jats:ext-link>).<\/jats:p>\n                  <jats:p>This work was supported by Arthritis Research UK (Grant 18769).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2016-014013","type":"journal-article","created":{"date-parts":[[2017,6,26]],"date-time":"2017-06-26T20:10:43Z","timestamp":1498507843000},"page":"e014013","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Imaging pain relief in osteoarthritis (IPRO): protocol of a double-blind randomised controlled mechanistic study assessing pain relief and prediction of duloxetine treatment outcome"],"prefix":"10.1136","volume":"7","clinical-trial-number":[{"clinical-trial-number":"nct02208778","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Diane","family":"Reckziegel","sequence":"first","affiliation":[{"name":"Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK"},{"name":"Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK"},{"name":"Division of Clinical Neuroscience, Radiological Sciences, University of Nottingham, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Bailey","sequence":"additional","affiliation":[{"name":"Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK"},{"name":"Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK"},{"name":"Division of Clinical Neuroscience, Radiological Sciences, University of Nottingham, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William J","family":"Cottam","sequence":"additional","affiliation":[{"name":"Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK"},{"name":"Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK"},{"name":"Division of Clinical Neuroscience, Radiological Sciences, University of Nottingham, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher R","family":"Tench","sequence":"additional","affiliation":[{"name":"Division of Clinical Neuroscience, Clinical Neurology, University of Nottingham, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi P","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK"},{"name":"Division of Clinical Neuroscience, Anaesthesia and Critical Care, University of Nottingham, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A","family":"Walsh","sequence":"additional","affiliation":[{"name":"Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK"},{"name":"Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger D","family":"Knaggs","sequence":"additional","affiliation":[{"name":"Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK"},{"name":"School of Pharmacy, University of Nottingham, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothee P","family":"Auer","sequence":"additional","affiliation":[{"name":"Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK"},{"name":"Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK"},{"name":"Division of Clinical Neuroscience, Radiological Sciences, University of Nottingham, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2017,6,26]]},"reference":[{"key":"2025101811594091000_7.6.e014013.1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204763"},{"key":"2025101811594091000_7.6.e014013.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2014.01.003"},{"key":"2025101811594091000_7.6.e014013.3","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2011-000435","article-title":"What proportion of patients report long-term pain after total hip or knee replacement for osteoarthritis? 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