title: An opposite-direction modulation of the COMT Val158Met polymorphism on the clinical response to intrathecal morphine and triptans.
abstract: Genetic variation in the COMT gene is thought to have clinical implications for pain perception and pain treatment. In the present study, we first evaluated the association between COMT rs4680 and the analgesic response to intrathecal morphine in patients with chronic low back pain to provide confirmation of previously reported positive findings. Next, we assessed the relationship between rs4680 and headache response to triptans in 2 independent cohorts of migraine patients. In patients with chronic low back pain (n = 74), logistic stepwise regression analysis showed that age (odds ratio [OR]: .90, 95% confidence interval [CI]: .85-.96, P = .002) and the presence of the COMT Met allele (vs Val/Val, OR: .21, 95% CI: .04-.98, P = .048) were predictive factors for lower risk of poor analgesic response to intrathecal morphine. Intriguingly, in migraine patients, the COMT rs4680 polymorphism influenced headache response to triptans in the opposite direction. Indeed, in an exploratory cohort of migraine patients without aura (n = 75), homozygous carriers of the COMT 158Met allele were found at increased risk to be poor responders to frovatriptan when compared to homozygous patients for the Val allele (OR: 5.20, 95% CI: 1.25-21.57, P = .023). In the validation cohort of migraine patients treated with triptans other than frovatriptan (n = 123), logistic stepwise regression analysis showed that use of prophylactic medications (OR: .43, 95% CI: .19-.99, P = .048) and COMT Met/Met genotype (vs Val/Val, OR: 4.29, 95% CI: 1.10-16.71, P = .036) were independent risk factors for poor response to triptans.
  
  
  CONCLUSIONS
  This study highlights the importance of COMT rs4680 in influencing the clinical response to drugs used for chronic pain, including opioid analgesics and triptans. These findings also underline a complex relationship between COMT genotypes and pain responder status.
authors.affiliation: Università del Piemonte Orientale "A. Avogadro," Dipartimento di Scienze del Farmaco and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Novara, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cargnin
authors.forename: Francesco
authors.initials: F
authors.lastname: Magnani
authors.forename: Michele
authors.initials: M
authors.lastname: Viana
authors.forename: Cristina
authors.initials: C
authors.lastname: Tassorelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Mittino
authors.forename: Roberto
authors.initials: R
authors.lastname: Cantello
authors.forename: Grazia
authors.initials: G
authors.lastname: Sances
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nappi
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Canonico
authors.forename: Armando A
authors.initials: AA
authors.lastname: Genazzani
authors.forename: William
authors.initials: W
authors.lastname: Raffaeli
authors.forename: Salvatore
authors.initials: S
authors.lastname: Terrazzino
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D002227:Carbazoles / Q000008:administration & dosage / Q000627:therapeutic use; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007278:Injections, Spinal; D017116:Low Back Pain / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use*; D015999:Multivariate Analysis; D010146:Pain / Q000188:drug therapy* / Q000235:genetics*; D010147:Pain Measurement / Q000187:drug effects; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011237:Predictive Value of Tests; D016896:Treatment Outcome; D014363:Tryptamines / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D002227:Carbazoles; D014363:Tryptamines; D009020:Morphine; D002394:Catechol O-Methyltransferase; C108128:frovatriptan
keywords: COMT polymorphism; Low back pain; migraine; morphine; response; triptans