title: COMTandOPRM1Genotype Associations with Daily Knee Pain Variability and Activity Induced Pain.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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 Met158allele ofCOMTrs4680 (A-A or A-G) and one or more copies of the Asp40allele ofOPRM1rs1799971 (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.
  
  
  METHODS
  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 modeling 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.
  
  
  RESULTS
  RegardingOPRM1rs1799971 (Asn40Asp), patients with two copies of the Asn40allele showed the greatest day-to-day pain variability. RegardingCOMTrs4680 (Val158Met), 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 toCOMTrs4680, orOPRM1rs1799971.
  
  
  CONCLUSIONS
  This study provides preliminary evidence that patients with certain genotypes forCOMTrs4680 andOPRM1rs1799971 (G-G and A-A, respectively) experience more variability in their day-to-day pain and exacerbation of pain after daily physical activity compared to patients with other genotypes. Our findings should be replicated in larger study populations.
  
  
  CONCLUSIONS
  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.
authors: The Pennsylvania State University, PennsylvaniaUnited States.
authors: Lynn M
authors: LM
authors: Martire
authors: The Pennsylvania State University, PennsylvaniaUnited States.
authors: Stephanie J
authors: SJ
authors: Wilson
authors: University of South Florida, South FloridaUnited States.
authors: Brent J
authors: BJ
authors: Small
authors: University of Pittsburgh, PittsburghUnited States.
authors: Yvette P
authors: YP
authors: Conley
authors: Penn State College of Medicine, PennUnited States.
authors: Piotr K
authors: PK
authors: Janicki
authors: The Pennsylvania State University, PennsylvaniaUnited States.
authors: Martin J
authors: MJ
authors: Sliwinski
keywords: ambulatory; genetics; osteoarthritis; pain; physical activity