{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T09:22:27Z","timestamp":1768900947345,"version":"3.49.0"},"reference-count":49,"publisher":"Georg Thieme Verlag KG","issue":"06","license":[{"start":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T00:00:00Z","timestamp":1699315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Musculoskelet Radiol"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Accurately identifying the peripheral pain generator in patients with chronic pain remains a major challenge for modern medicine. Millions of patients around the world suffer endlessly from difficult-to-manage debilitating pain because of very limited diagnostic tests and a paucity of pain therapies. To help these patients, we have developed a novel clinical molecular imaging approach, and, in its early stages, it has been shown to accurately identify the exact site of pain generation using an imaging biomarker for the sigma-1 receptor and positron emission tomography\/magnetic resonance imaging. We hope the description of the work in this article can help others begin their own pain imaging programs at their respective institutions.<\/jats:p>","DOI":"10.1055\/s-0043-1775744","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T23:43:57Z","timestamp":1699400637000},"page":"601-617","source":"Crossref","is-referenced-by-count":3,"title":["A Practical Guide to Sigma-1 Receptor Positron Emission Tomography\/Magnetic Resonance Imaging: A New Clinical Molecular Imaging Method to Identify Peripheral Pain Generators in Patients with Chronic Pain"],"prefix":"10.1055","volume":"27","author":[{"given":"Bin","family":"Shen","sequence":"additional","affiliation":[{"name":"Cyclotron Radiochemistry Facility, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daehyun","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of California San Francisco School of Medicine, San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessa","family":"Castillo","sequence":"additional","affiliation":[{"name":"Radiochemistry Facility, University of California San Francisco School of Medicine, San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandip","family":"Biswal","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2023,11,7]]},"reference":[{"issue":"08","key":"ref1","doi-asserted-by":"crossref","first-page":"625","DOI":"10.3949\/ccjm.71.8.625","article-title":"Cancer pain: how to measure the fifth vital sign","volume":"71","author":"M P Davis","year":"2004","journal-title":"Cleve Clin J Med"},{"issue":"01","key":"ref2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ejphar.2005.01.036","article-title":"Formalin-induced pain is reduced in sigma(1) receptor knockout mice","volume":"511","author":"C M Cend\u00e1n","year":"2005","journal-title":"Eur J Pharmacol"},{"issue":"05","key":"ref3","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1038\/bjp.2008.159","article-title":"Activation of the spinal sigma-1 receptor enhances NMDA-induced pain via PKC- and PKA-dependent phosphorylation of the NR1 subunit in mice","volume":"154","author":"H W Kim","year":"2008","journal-title":"Br J Pharmacol"},{"issue":"03","key":"ref4","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.pain.2009.05.013","article-title":"Sigma-1 receptors regulate activity-induced spinal sensitization and neuropathic pain after peripheral nerve injury","volume":"145","author":"B Puente","year":"2009","journal-title":"Pain"},{"issue":"02","key":"ref5","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.neulet.2010.04.041","article-title":"Sigma-1 receptor-induced increase in murine spinal NR1 phosphorylation is mediated by the PKCalpha and epsilon, but not the PKCzeta, isoforms","volume":"477","author":"D H Roh","year":"2010","journal-title":"Neurosci Lett"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ejphar.2013.01.068","article-title":"Sigma 1 receptor: a new therapeutic target for pain","volume":"716","author":"D Zamanillo","year":"2013","journal-title":"Eur J Pharmacol"},{"issue":"12","key":"ref7","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.2967\/jnumed.117.192641","article-title":"Biodistribution and radiation dosimetry of 18F-FTC-146 in humans","volume":"58","author":"T Hj\u00f8rnevik","year":"2017","journal-title":"J Nucl Med"},{"issue":"01","key":"ref8","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2967\/jnumed.113.120261","article-title":"Evaluation of \u03c3-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET","volume":"55","author":"M L James","year":"2014","journal-title":"J Nucl Med"},{"issue":"11","key":"ref9","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.7150\/thno.19378","article-title":"Visualizing nerve injury in a neuropathic pain model with [18F]FTC-146 PET\/MRI","volume":"7","author":"B Shen","year":"2017","journal-title":"Theranostics"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.2147\/JPR.S167839","article-title":"Successful treatment of chronic knee pain following localization by a sigma-1 receptor radioligand and PET\/MRI: a case report","volume":"11","author":"P W Cipriano","year":"2018","journal-title":"J Pain Res"},{"issue":"04","key":"ref12","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1124\/mol.109.057083","article-title":"Sigma 1 receptor modulation of G-protein-coupled receptor signaling: potentiation of opioid transduction independent from receptor binding","volume":"77","author":"F J Kim","year":"2010","journal-title":"Mol Pharmacol"},{"issue":"09","key":"ref13","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1002\/ar.24061","article-title":"Sigma-1 receptor expression in DRG neurons during a carrageenan-provoked inflammation","volume":"302","author":"L Jer\u010di\u0107","year":"2019","journal-title":"Anat Rec (Hoboken)"},{"issue":"04","key":"ref14","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1002\/ejp.774","article-title":"Role of peripheral sigma-1 receptors in ischaemic pain: potential interactions with ASIC and P2X receptors","volume":"20","author":"S G Kwon","year":"2016","journal-title":"Eur J Pain"},{"issue":"01","key":"ref15","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/s13311-017-0572-5","article-title":"Efficacy of a novel sigma-1 receptor antagonist for oxaliplatin-induced neuropathy: a randomized, double-blind, placebo-controlled phase IIa clinical trial","volume":"15","author":"J Bruna","year":"2018","journal-title":"Neurotherapeutics"},{"issue":"03","key":"ref16","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1097\/FBP.0000000000000038","article-title":"S1RA, a selective sigma-1 receptor antagonist, inhibits inflammatory pain in the carrageenan and complete Freund's adjuvant models in mice","volume":"25","author":"G Gris","year":"2014","journal-title":"Behav Pharmacol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"24591","DOI":"10.1038\/srep24591","article-title":"The selective sigma-1 receptor antagonist E-52862 attenuates neuropathic pain of different aetiology in rats","volume":"6","author":"G Gris","year":"2016","journal-title":"Sci Rep"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1744-8069-10-11","article-title":"Genetic inactivation and pharmacological blockade of sigma-1 receptors prevent paclitaxel-induced sensory-nerve mitochondrial abnormalities and neuropathic pain in mice","volume":"10","author":"F R Nieto","year":"2014","journal-title":"Mol Pain"},{"issue":"07","key":"ref19","doi-asserted-by":"crossref","first-page":"E1657","DOI":"10.1073\/pnas.1715972115","article-title":"TRPV1 channels and the progesterone receptor Sig-1R interact to regulate pain","volume":"115","author":"M Ort\u00edz-Renter\u00eda","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"02","key":"ref20","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1124\/jpet.114.214320","article-title":"Sigma-1 receptor antagonism restores injury-induced decrease of voltage-gated Ca2+ current in sensory neurons","volume":"350","author":"B Pan","year":"2014","journal-title":"J Pharmacol Exp Ther"},{"issue":"10","key":"ref21","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1089\/ars.2014.5993","article-title":"The \u03c31 receptor engages the redox-regulated HINT1 protein to bring opioid analgesia under NMDA receptor negative control","volume":"22","author":"M Rodr\u00edguez-Mu\u00f1oz","year":"2015","journal-title":"Antioxid Redox Signal"},{"issue":"19","key":"ref22","doi-asserted-by":"crossref","first-page":"3855","DOI":"10.1007\/s00213-014-3524-3","article-title":"Sigma-1 receptor inhibition reverses acute inflammatory hyperalgesia in mice: role of peripheral sigma-1 receptors","volume":"231","author":"M A Tejada","year":"2014","journal-title":"Psychopharmacology (Berl)"},{"issue":"02","key":"ref23","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/syn.20281","article-title":"[123I]TPCNE\u2013a novel SPET tracer for the sigma-1 receptor: first human studies and in vivo haloperidol challenge","volume":"60","author":"J M Stone","year":"2006","journal-title":"Synapse"},{"key":"ref24","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-59745-510-7","volume-title":"The Genetics and Molecular Biology of Neural Tumors","author":"A A Sandberg","year":"2008"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"17004","DOI":"10.1038\/nrdp.2017.4","article-title":"Neurofibromatosis type 1","volume":"3","author":"D H Gutmann","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1016\/S0140-6736(09)60259-2","article-title":"Neurofibromatosis type 2","volume":"373","author":"A R Asthagiri","year":"2009","journal-title":"Lancet"},{"issue":"11","key":"ref27","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1136\/jnnp-2018-318538","article-title":"Schwannomatosis: a genetic and epidemiological study","volume":"89","author":"D G Evans","year":"2018","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref28","volume-title":"Neurofibromatosis Fact Sheet","author":"National Institute of Neuological Disorders and Stroke","year":"2020"},{"key":"ref29","first-page":"975364","article-title":"Physical, cognitive, and psychosocial predictors of functional disability and health-related quality of life in adolescents with neurofibromatosis-1","volume":"2012","author":"M M Garwood","year":"2012","journal-title":"Pain Res Treat"},{"issue":"09","key":"ref30","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1002\/ajmg.a.37123","article-title":"Pain interference in youth with neurofibromatosis type 1 and plexiform neurofibromas and relation to disease severity, social-emotional functioning, and quality of life","volume":"167A","author":"P L Wolters","year":"2015","journal-title":"Am J Med Genet A"},{"issue":"06","key":"ref31","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1007\/s10897-015-9829-5","article-title":"The impact of neurofibromatosis type 1 on the health and wellbeing of Australian adults","volume":"24","author":"H A Crawford","year":"2015","journal-title":"J Genet Couns"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.2147\/JPR.S209540","article-title":"Pain symptomology, functional impact, and treatment of people with neurofibromatosis type 1","volume":"12","author":"F D Buono","year":"2019","journal-title":"J Pain Res"},{"issue":"04","key":"ref33","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.3171\/2020.8.JNS202885","article-title":"Analysis of the effect of intraoperative neuromonitoring during resection of benign nerve sheath tumors on gross total resection and neurological complications","volume":"135","author":"T J Wilson","year":"2021","journal-title":"J Neurosurg"},{"issue":"02","key":"ref34","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1093\/pm\/pnab315","article-title":"Neurovascular, muscle, and skin changes on [18F]FDG PET\/MRI in complex regional pain syndrome of the foot: a prospective clinical study","volume":"23","author":"D Yoon","year":"2022","journal-title":"Pain Med"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1136\/bmj.332.7555.1430","article-title":"Diagnosis and treatment of low back pain","volume":"332","author":"B W Koes","year":"2006","journal-title":"BMJ"},{"issue":"05","key":"ref36","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1056\/NEJM200102013440508","article-title":"Low back pain","volume":"344","author":"R A Deyo","year":"2001","journal-title":"N Engl J Med"},{"issue":"10","key":"ref37","doi-asserted-by":"crossref","first-page":"3072","DOI":"10.1002\/art.24853","article-title":"Prevalence of and screening for serious spinal pathology in patients presenting to primary care settings with acute low back pain","volume":"60","author":"N Henschke","year":"2009","journal-title":"Arthritis Rheum"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/S0140-6736(16)30970-9","article-title":"Non-specific low back pain","volume":"389","author":"C Maher","year":"2017","journal-title":"Lancet"},{"issue":"04","key":"ref39","doi-asserted-by":"crossref","first-page":"811","DOI":"10.3174\/ajnr.A4173","article-title":"Systematic literature review of imaging features of spinal degeneration in asymptomatic populations","volume":"36","author":"W Brinjikji","year":"2015","journal-title":"AJNR Am J Neuroradiol"},{"issue":"14","key":"ref40","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1097\/BRS.0b013e3182443855","article-title":"Association of Modic changes, Schmorl's nodes, spondylolytic defects, high-intensity zone lesions, disc herniations, and radial tears with low back symptom severity among young Finnish adults","volume":"37","author":"J Takatalo","year":"2012","journal-title":"Spine"},{"issue":"03","key":"ref41","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/S0885-3924(01)00320-7","article-title":"Opioids and the treatment of chronic pain in a primary care sample","volume":"22","author":"N J Adams","year":"2001","journal-title":"J Pain Symptom Manage"},{"issue":"03","key":"ref42","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1046\/j.1525-1497.2002.10435.x","article-title":"Use of opioid medications for chronic noncancer pain syndromes in primary care","volume":"17","author":"M C Reid","year":"2002","journal-title":"J Gen Intern Med"},{"issue":"07","key":"ref43","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.pain.2013.03.011","article-title":"Opioid use among low back pain patients in primary care: is opioid prescription associated with disability at 6-month follow-up?","volume":"154","author":"J Ashworth","year":"2013","journal-title":"Pain"},{"issue":"12","key":"ref44","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1097\/BRS.0000000000002964","article-title":"Preoperative opioids and 1-year patient reported outcomes after spine surgery","volume":"44","author":"J M Hills","year":"2019","journal-title":"Spine (Phila Pa 1976)"},{"issue":"06","key":"ref45","doi-asserted-by":"crossref","first-page":"717","DOI":"10.3122\/jabfm.2011.06.100232","article-title":"Opioids for back pain patients: primary care prescribing patterns and use of services","volume":"24","author":"R A Deyo","year":"2011","journal-title":"J Am Board Fam Med"},{"issue":"02","key":"ref46","doi-asserted-by":"crossref","first-page":"E104","DOI":"10.1097\/BRS.0000000000001715","article-title":"Prolonged preoperative opioid therapy associated with poor return to work rates after single-level cervical fusion for radiculopathy for patients receiving workers' compensation benefits","volume":"42","author":"M Faour","year":"2017","journal-title":"Spine"},{"issue":"11","key":"ref47","doi-asserted-by":"crossref","first-page":"e89","DOI":"10.2106\/JBJS.M.00865","article-title":"Preoperative opioid use as a predictor of adverse postoperative self-reported outcomes in patients undergoing spine surgery","volume":"96","author":"D Lee","year":"2014","journal-title":"j Bone Joint Surg Am"},{"issue":"03","key":"ref48","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0304-3959(00)00339-0","article-title":"Defining the clinically important difference in pain outcome measures","volume":"88","author":"J T Farrar","year":"2000","journal-title":"Pain"},{"issue":"02","key":"ref49","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0304-3959(87)91074-8","article-title":"The short-form McGill Pain Questionnaire","volume":"30","author":"R Melzack","year":"1987","journal-title":"Pain"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1186\/2193-1801-2-628","article-title":"Clinical characteristics of pain originating from intra-articular structures of the knee joint in patients with medial knee osteoarthritis","volume":"2","author":"M Ikeuchi","year":"2013","journal-title":"Springerplus"}],"container-title":["Seminars in Musculoskeletal Radiology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0043-1775744.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T23:44:21Z","timestamp":1699400661000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0043-1775744"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,7]]},"references-count":49,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2023,11,7]]},"published-print":{"date-parts":[[2023,12]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0043-1775744","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["1089-7860","1098-898X"],"issn-type":[{"value":"1089-7860","type":"print"},{"value":"1098-898X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,7]]}}}