{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T08:35:40Z","timestamp":1786869340328,"version":"build-2736575974"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T00:00:00Z","timestamp":1607385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100005831","name":"Foundation for Anesthesia Education and Research","doi-asserted-by":"publisher","award":["Research Fellowship Grant"],"award-info":[{"award-number":["Research Fellowship Grant"]}],"id":[{"id":"10.13039\/100005831","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01-CX-000816"],"award-info":[{"award-number":["I01-CX-000816"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01-CX- 001652"],"award-info":[{"award-number":["I01-CX- 001652"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["U19AR076737"],"award-info":[{"award-number":["U19AR076737"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["UH2AR076724"],"award-info":[{"award-number":["UH2AR076724"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Reported pain intensity depends not only on stimulus intensity but also on previously experienced pain. A painfully hot temperature applied to the skin evokes a lower subjective pain intensity if immediately preceded by a higher temperature, a phenomenon called offset analgesia. Previous work indicated that prior pain experience can also increase subsequent perceived pain intensity. Therefore, we examined whether a given noxious stimulus is experienced as more intense when it is preceded by an increase from a lower temperature. Using healthy volunteer subjects, we observed a disproportionate increase in pain intensity at a given stimulus intensity when this intensity is preceded by a rise from a lower intensity. This disproportionate increase is similar in magnitude to that of offset analgesia. We call this effect onset hyperalgesia. Control stimuli, in which a noxious temperature is held constant, demonstrate that onset hyperalgesia is distinct from receptor or central sensitization. The absolute magnitudes of offset analgesia and onset hyperalgesia correlate with each other but not with the noxious stimulus temperature. Finally, the magnitude of both offset analgesia and onset hyperalgesia depends on preceding temperature changes. Overall, this study demonstrates that the perceptual effect of a noxious thermal stimulus is influenced in a bidirectional manner depending upon both the intensity and direction of change of the immediately preceding thermal stimulus.<\/jats:p>","DOI":"10.1371\/journal.pone.0231124","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T14:20:54Z","timestamp":1607437254000},"page":"e0231124","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["Onset hyperalgesia and offset analgesia: Transient increases or decreases of noxious thermal stimulus intensity robustly modulate subsequent perceived pain intensity"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0171-3411","authenticated-orcid":true,"given":"Benedict J.","family":"Alter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4244-3235","authenticated-orcid":true,"given":"Mya Sandi","family":"Aung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina A.","family":"Strigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard L.","family":"Fields","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,12,8]]},"reference":[{"key":"pone.0231124.ref001","first-page":"241","volume-title":"Psychological and neural mechanisms of pain","author":"DD Price","year":"1988"},{"key":"pone.0231124.ref002","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/nrn3976","article-title":"The neuroscience of placebo effects: connecting context, learning and health","volume":"16","author":"TD Wager","year":"2015","journal-title":"Nature Reviews Neuroscience"},{"issue":"16","key":"pone.0231124.ref003","doi-asserted-by":"crossref","first-page":"4437","DOI":"10.1523\/JNEUROSCI.4463-05.2006","article-title":"Isolating the modulatory effect of expectation on pain transmission: a functional magnetic resonance imaging study","volume":"26","author":"JR Keltner","year":"2006","journal-title":"J Neurosci"},{"key":"pone.0231124.ref004","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1146\/annurev-neuro-072116-031132","article-title":"The Cognitive Neuroscience of Placebo Effects: Concepts, Predictions, and Physiology","volume":"40","author":"S Geuter","year":"2017","journal-title":"Annu Rev Neurosci"},{"key":"pone.0231124.ref005","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1353\/pbm.2005.0054","article-title":"Pain and the placebo: what we have learned","volume":"48","author":"GA Hoffman","year":"2005","journal-title":"Perspect Biol Med"},{"issue":"6","key":"pone.0231124.ref006","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.neuron.2014.02.042","article-title":"Placebo analgesia: a predictive coding perspective","volume":"81","author":"C Buchel","year":"2014","journal-title":"Neuron"},{"key":"pone.0231124.ref007","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.pain.2007.04.014","article-title":"Offset analgesia: A temporal contrast mechanism for nociceptive information","volume":"134","author":"MD Yelle","year":"2008","journal-title":"Pain"},{"key":"pone.0231124.ref008","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1152\/jn.00730.2001","article-title":"Transient analgesia evoked by noxious stimulus offset","volume":"87","author":"JD Grill","year":"2002","journal-title":"Journal of neurophysiology"},{"issue":"1","key":"pone.0231124.ref009","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1002\/ejp.1110","article-title":"Offset analgesia: The role of peripheral and central mechanisms","volume":"22","author":"D Ligato","year":"2018","journal-title":"Eur J Pain"},{"key":"pone.0231124.ref010","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/j.neuroimage.2009.04.032","article-title":"Offset analgesia is mediated by activation in the region of the periaqueductal grey and rostral ventromedial medulla","volume":"47","author":"SWG Derbyshire","year":"2009","journal-title":"NeuroImage"},{"key":"pone.0231124.ref011","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1016\/j.pain.2012.02.035","article-title":"Opioid-independent mechanisms supporting offset analgesia and temporal sharpening of nociceptive information","volume":"153","author":"KT Martucci","year":"2012","journal-title":"Pain"},{"key":"pone.0231124.ref012","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.pain.2011.11.010","article-title":"Differential effects of experimental central sensitization on the time-course and magnitude of offset analgesia","volume":"153","author":"KT Martucci","year":"2012","journal-title":"Pain"},{"key":"pone.0231124.ref013","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1016\/j.pain.2014.07.008","article-title":"Distinct brain mechanisms support spatial vs temporal filtering of nociceptive information","volume":"155","author":"H Nahman-Averbuch","year":"2014","journal-title":"Pain"},{"issue":"1","key":"pone.0231124.ref014","doi-asserted-by":"crossref","first-page":"3894","DOI":"10.1038\/s41598-017-04009-9","article-title":"A central mechanism enhances pain perception of noxious thermal stimulus changes","volume":"7","author":"B Petre","year":"2017","journal-title":"Sci Rep"},{"issue":"10","key":"pone.0231124.ref015","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1097\/j.pain.0000000000000250","article-title":"Distinct temporal filtering mechanisms are engaged during dynamic increases and decreases of noxious stimulus intensity","volume":"156","author":"CD Morch","year":"2015","journal-title":"Pain"},{"key":"pone.0231124.ref016","unstructured":"Barratt W. The Barratt Simplified Measure of Social Status (BSMSS) measuring SES. 2006 [cited 2017]. http:\/\/socialclassoncampus.blogspot.com\/2012\/06\/barratt-simplified-measure-of-social.html."},{"issue":"4","key":"pone.0231124.ref017","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1590\/1516-4446-2012-1048","article-title":"Psychometric properties of the Beck Depression Inventory-II: a comprehensive review","volume":"35","author":"YP Wang","year":"2013","journal-title":"Revista brasileira de psiquiatria (Sao Paulo, Brazil: 1999)"},{"issue":"3","key":"pone.0231124.ref018","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1207\/s15327906mbr1003_6","article-title":"Validation of the State-Trait Distinction in Anxiety Research","volume":"10","author":"E Gaudry","year":"1975","journal-title":"Multivariate behavioral research"},{"issue":"12","key":"pone.0231124.ref019","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1016\/j.jpain.2010.03.014","article-title":"Psychological and sensory predictors of experimental thermal pain: a multifactorial model","volume":"11","author":"CJ Starr","year":"2010","journal-title":"J Pain"},{"key":"pone.0231124.ref020","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1037\/1040-3590.7.4.524","article-title":"The Pain Catastrophizing Scale: Development and validation","volume":"7","author":"MJL Sullivan","year":"1995","journal-title":"Psychological Assessment"},{"issue":"6","key":"pone.0231124.ref021","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1002\/1097-4679(199511)51:6<768::AID-JCLP2270510607>3.0.CO;2-1","article-title":"Factor structure of the Barratt impulsiveness scale","volume":"51","author":"JH Patton","year":"1995","journal-title":"Journal of clinical psychology"},{"key":"pone.0231124.ref022","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.2147\/NDT.S66209","article-title":"Aggression, impulsivity, and suicide risk in benign chronic pain patients\u2014A cross-sectional study","volume":"10","author":"F Margari","year":"2014","journal-title":"Neuropsychiatric disease and treatment"},{"issue":"5","key":"pone.0231124.ref023","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1016\/j.addbeh.2013.01.020","article-title":"Impulsivity but not sensation seeking is associated with opioid analgesic misuse risk in patients with chronic pain","volume":"38","author":"EN Marino","year":"2013","journal-title":"Addict Behav"},{"key":"pone.0231124.ref024","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.jpain.2009.08.009","article-title":"Situational Versus Dispositional Measurement of Catastrophizing: Associations With Pain Responses in Multiple Samples","volume":"11","author":"CM Campbell","year":"2010","journal-title":"Journal of Pain"},{"key":"pone.0231124.ref025","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1097\/ALN.0b013e31822fd03a","article-title":"Offset analgesia in neuropathic pain patients and effect of treatment with morphine and ketamine","volume":"115","author":"M Niesters","year":"2011","journal-title":"Anesthesiology"},{"key":"pone.0231124.ref026","doi-asserted-by":"crossref","first-page":"1744806918767512","DOI":"10.1177\/1744806918767512","article-title":"Attenuation of offset analgesia is associated with suppression of descending pain modulatory and reward systems in patients with chronic pain","volume":"14","author":"S Zhang","year":"2018","journal-title":"Mol Pain"},{"issue":"2","key":"pone.0231124.ref027","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1097\/AJP.0000000000000657","article-title":"The Magnitude of Offset Analgesia as a Measure of Endogenous Pain Modulation in Healthy Participants and Patients With Chronic Pain: A Systematic Review and Meta-Analysis","volume":"35","author":"TM Szikszay","year":"2019","journal-title":"Clin J Pain"},{"issue":"2","key":"pone.0231124.ref028","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jbi.2008.08.010","article-title":"Research electronic data capture (REDCap)\u2014a metadata-driven methodology and workflow process for providing translational research informatics support","volume":"42","author":"PA Harris","year":"2009","journal-title":"J Biomed Inform"},{"issue":"8","key":"pone.0231124.ref029","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.ejpain.2008.01.008","article-title":"Enhancement of offset analgesia during sequential testing","volume":"12","author":"SW Derbyshire","year":"2008","journal-title":"Eur J Pain"},{"issue":"12","key":"pone.0231124.ref030","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1016\/j.jpain.2017.08.003","article-title":"Loss of Temporal Inhibition of Nociceptive Information Is Associated With Aging and Bodily Pain","volume":"18","author":"KM Naugle","year":"2017","journal-title":"J Pain"},{"issue":"5","key":"pone.0231124.ref031","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1152\/jn.00335.2018","article-title":"No temporal contrast enhancement of simple decreases in noxious heat","volume":"121","author":"B Beck","year":"2019","journal-title":"J Neurophysiol"},{"issue":"10","key":"pone.0231124.ref032","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1097\/j.pain.0000000000000989","article-title":"Disrupted offset analgesia distinguishes patients with chronic pain from healthy controls","volume":"158","author":"H Kobinata","year":"2017","journal-title":"Pain"},{"issue":"33","key":"pone.0231124.ref033","doi-asserted-by":"crossref","first-page":"10264","DOI":"10.1523\/JNEUROSCI.4648-08.2009","article-title":"Temporal filtering of nociceptive information by dynamic activation of endogenous pain modulatory systems","volume":"29","author":"MD Yelle","year":"2009","journal-title":"J Neurosci"},{"key":"pone.0231124.ref034","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.neuroimage.2018.09.003","article-title":"Evidence for a spinal involvement in temporal pain contrast enhancement","volume":"183","author":"C Sprenger","year":"2018","journal-title":"Neuroimage"},{"issue":"12","key":"pone.0231124.ref035","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1097\/j.pain.0000000000000321","article-title":"The influence of offset analgesia on the onset and offset of pain in patients with fibromyalgia","volume":"156","author":"LC Oudejans","year":"2015","journal-title":"Pain"},{"key":"pone.0231124.ref036","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s00221-013-3580-7","article-title":"Psychophysical testing of spatial and temporal dimensions of endogenous analgesia: conditioned pain modulation and offset analgesia","volume":"228","author":"L Honigman","year":"2013","journal-title":"Experimental brain research"},{"key":"pone.0231124.ref037","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1016\/j.pain.2013.07.015","article-title":"Offset analgesia is reduced in older adults","volume":"154","author":"KM Naugle","year":"2013","journal-title":"Pain"},{"issue":"Suppl 1","key":"pone.0231124.ref038","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1097\/j.pain.0000000000001272","article-title":"How expectations influence pain","volume":"159","author":"HL Fields","year":"2018","journal-title":"Pain"},{"key":"pone.0231124.ref039","first-page":"449","volume-title":"Proceedings of the 11th World Congress on Pain","author":"HL Fields","year":"2006"},{"key":"pone.0231124.ref040","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.neuron.2015.06.005","article-title":"Nociception, Pain, Negative Moods, and Behavior Selection","volume":"87","author":"MN Baliki","year":"2015","journal-title":"Neuron"},{"issue":"1","key":"pone.0231124.ref041","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.cub.2015.10.066","article-title":"Dissociable Learning Processes Underlie Human Pain Conditioning","volume":"26","author":"S Zhang","year":"2016","journal-title":"Curr Biol"},{"issue":"8","key":"pone.0231124.ref042","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jpain.2006.02.005","article-title":"Advanced continuous-contact heat pulse design for efficient temporal summation of second pain (windup)","volume":"7","author":"R Staud","year":"2006","journal-title":"J Pain"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0231124","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T14:21:38Z","timestamp":1607437298000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0231124"}},"subtitle":[],"editor":[{"given":"Shaheen E","family":"Lakhan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,12,8]]},"references-count":42,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0231124","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.03.18.996769","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,8]]}}}