title: Central pain sensitization, COMT Val158Met polymorphism, and emotional factors in fibromyalgia.
abstract: Neurobiological evidence points to altered central nervous system processing of nociceptive stimuli in fibromyalgia. Enzymes like catechol-O-methyl-transferase (COMT) are involved in the elimination of catecholamines playing a possible role in central sensitization and pain. We used quantitative sensory testing to evidence central sensitization in fibromyalgia patients and test whether COMTVal158Met polymorphism, associated with a reduction in enzyme activity, plays a role in sensitized patients. Pain evaluation and quantitative sensory testing were performed including the spinal nociceptive flexion reflex, a physiologic correlate for the evaluation of central nociceptive pathways. Quality of life and distress questionnaires were used. A total of 137 fibromyalgia patients were assessed and compared to 99 matched controls. Central sensitization (nociceptive flexion reflex <27 mA) was present in 95/134 (71%) patients. Among them, COMT p.Val158Met polymorphism displayed a significant linear "genotype effect" (P = .033), with the Met/Met (mean = 17.8 ± 4.8 mA) and Val/Val (mean = 21.4 ± 4.6 mA) subgroups at the opposite ends of the nociceptive flexion reflex threshold (Met/Met vs Val/Val P = .015) and the Val/Met subgroup (mean = 19 ± 4.9 mA) in between (Val/Met vs Val/Val P = .041). Spontaneous moderate to severe pain was more likely to be associated with COMT Met/Met genotype. Patients showed important emotional distress compared to controls. In sensitized patients, the COMT Met/Met subgroup showed systematically-though not significantly-worse scores for all psychological variables.
  
  
  CONCLUSIONS
  The association between COMT p.Val158Met polymorphism and central sensitization in fibromyalgia is essential as it refers to the severity of central sensitization and may be a risk factor for treatment outcome.
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland; Multidisciplinary Pain Center, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland. Electronic address: Jules.Desmeules@hcuge.ch.
authors.forename: Jules
authors.initials: J
authors.lastname: Desmeules
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Chabert
authors.affiliation: Division of Laboratory Medicine, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland.
authors.forename: Michela
authors.initials: M
authors.lastname: Rebsamen
authors.affiliation: Institute for Social and Preventive Medicine, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Rapiti
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland; Multidisciplinary Pain Center, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland.
authors.forename: Valerie
authors.initials: V
authors.lastname: Piguet
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland; Multidisciplinary Pain Center, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland.
authors.forename: Marie
authors.initials: M
authors.lastname: Besson
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland; Multidisciplinary Pain Center, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Dayer
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland; Multidisciplinary Pain Center, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland; Division of General Medical Rehabilitation, Geneva University Hospitals, Faculty of Medicine, Geneva University, Geneva, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Cedraschi
mesh_terms: D000344:Afferent Pathways / Q000503:physiopathology; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D059333:Central Nervous System Sensitization / Q000235:genetics / Q000502:physiology; D003080:Cold Temperature; D004558:Electric Stimulation; D004644:Emotions; D005260:Female; D005356:Fibromyalgia / Q000150:complications / Q000235:genetics* / Q000523:psychology*; D060005:Genotyping Techniques; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology / Q000523:psychology; D011110:Polymorphism, Genetic; D011788:Quality of Life; D011795:Surveys and Questionnaires
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: Fibromyalgia; catechol-O-methyl-transferase polymorphism; central sensitization; psychological distress; spinal nociceptive flexion reflex