{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T14:21:45Z","timestamp":1768486905005,"version":"3.49.0"},"reference-count":25,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["clinicalkey.jp","scandinavianjournalpain.com","clinicalkey.com","clinicalkey.es","clinicalkey.com.au","clinicalkey.fr","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_j.sjpain.2015.07.004_s_001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Osteoarthritis (OA) of the knee is a common and increasingly prevalent condition that is one of the primary causes of chronic pain. Staying physically active protects against disability from knee OA but is also very challenging. A critical but unexamined question is whether patients at greatest risk for becoming less active are those with a genetic predisposition for greater sensitivity to daily pain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_j.sjpain.2015.07.004_s_002\">\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      We examined day-to-day variability in knee OA pain for patients with different variants of catechol-O-methyltransferase (COMT) and mu-opioid receptor (OPRM1) single nucleotide polymorphisms (SNPs), and whether patients with a specific genotype experience more pain following daily physical activity. We predicted that patients having one or more copies of the Met\n                      <jats:sup>158<\/jats:sup>\n                      allele of\n                      <jats:italic>COMT<\/jats:italic>\n                      rs4680 (A-A or A-G) and one or more copies of the Asp\n                      <jats:sup>40<\/jats:sup>\n                      allele of\n                      <jats:italic>OPRM1<\/jats:italic>\n                      rs1799971 (A-G or G-G) would show greater pain variability. We expected to see the same pattern for these SNPs with regard to moderation (i.e., exacerbation) of the activity-pain association.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_j.sjpain.2015.07.004_s_003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 120 knee OA patients reported on their pain 3 times per day over 22 days using handheld computers, and wore an accelerometer to capture daily physical activity. Multilevel modelling was used to examine the magnitude of within-person variability in pain by genetic group. We also examined whether lagged, within-patient associations between level of activity in the afternoon (i.e., minutes of moderate intensity activity, and number of steps) and knee pain at the end-of-day were moderated by between-patient differences in genotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_j.sjpain.2015.07.004_s_004\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Regarding\n                      <jats:italic>OPRM1<\/jats:italic>\n                      rs1799971 (Asn\n                      <jats:sup>40<\/jats:sup>\n                      Asp), patients with two copies of the Asn\n                      <jats:sup>40<\/jats:sup>\n                      allele showed the greatest day-to-day pain variability. Regarding\n                      <jats:italic>COMT<\/jats:italic>\n                      rs4680 (Val\n                      <jats:sup>158<\/jats:sup>\n                      Met), patients with the Val\/Val genotype showed the greatest pain variability and also experienced the greatest increase in pain as a result of physical activity. A similar pattern of findings across bi-directional temporal lags was consistent with a negative feedback loop between daily physical activity and pain according to genotype. Consistent with some previous studies, there were no significant between-person differences in daily pain when comparing patients according to COMTrs4680, or\n                      <jats:italic>OPRM1<\/jats:italic>\n                      rs1799971.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_j.sjpain.2015.07.004_s_005\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study provides preliminary evidence that patients with certain genotypes for\n                      <jats:italic>COMT<\/jats:italic>\n                      rs4680 and\n                      <jats:italic>OPRM1<\/jats:italic>\n                      rs1799971 (\n                      <jats:italic>G-G<\/jats:italic>\n                      and\n                      <jats:italic>A-A<\/jats:italic>\n                      , respectively) experience more variability in their day-today pain and exacerbation of pain after daily physical activity compared to patients with other genotypes. Our findings should be replicated in larger study populations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_j.sjpain.2015.07.004_s_006\">\n                    <jats:title>Implications<\/jats:title>\n                    <jats:p>Previous clinical research has focused primarily on differences in average level of pain between patients with and without a specific genotype. Assessment of within-person variability through repeated measurements in daily life enhances the reliability, power, and ecological validity of phenotypic measurement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_j.sjpain.2015.07.004_s_007\">\n                    <jats:title>Perspective<\/jats:title>\n                    <jats:p>\n                      This study provides preliminary evidence that patients with certain variations in the\n                      <jats:italic>COMT<\/jats:italic>\n                      and\n                      <jats:italic>OPRM1<\/jats:italic>\n                      SNPs experience more variability in their day-to-day pain and exacerbation of pain after daily physical activity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.sjpain.2015.07.004","type":"journal-article","created":{"date-parts":[[2015,8,13]],"date-time":"2015-08-13T05:15:42Z","timestamp":1439442942000},"page":"6-12","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":17,"title":["<i>COMT<\/i>\n                    and\n                    <i>OPRM1<\/i>\n                    genotype associations with daily knee pain variability and activity induced pain"],"prefix":"10.1515","volume":"10","author":[{"given":"Lynn M.","family":"Martire","sequence":"first","affiliation":[{"name":"The Pennsylvania State University , Pennsylvania United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie J.","family":"Wilson","sequence":"additional","affiliation":[{"name":"The Pennsylvania State University , Pennsylvania United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brent J.","family":"Small","sequence":"additional","affiliation":[{"name":"University of South Florida , South Florida United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvette P.","family":"Conley","sequence":"additional","affiliation":[{"name":"University of Pittsburgh , Pittsburgh United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr K.","family":"Janicki","sequence":"additional","affiliation":[{"name":"Penn State College of Medicine , Penn United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin J.","family":"Sliwinski","sequence":"additional","affiliation":[{"name":"The Pennsylvania State University , Pennsylvania United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2016,1,1]]},"reference":[{"key":"2025120909564031066_j_j.sjpain.2015.07.004_ref_001","doi-asserted-by":"crossref","unstructured":"Murphy  L, Schwartz TA, Helmick CG, Renner JB, Tudor  G, Koch  G, Dragomir  A, Kalsbeek WD, Luta  G, Jordan JM. 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