An opposite-direction modulation of the COMT val158met polymorphism on the clinical response to intrathecal morphine and triptans

Sarah Cargnin, Francesco Magnani, Michele Viana, Cristina Tassorelli, Daniela Mittino, Roberto Cantello, Grazia Sances, Giuseppe Nappi, Pier Luigi Canonico, Armando A. Genazzani, William Raffaeli, Salvatore Terrazzino

Research output: Contribution to journalArticle

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. Perspective: 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.

Original languageEnglish
Pages (from-to)1097-1106
Number of pages10
JournalJournal of Pain
Volume14
Issue number10
DOIs
Publication statusPublished - Oct 2013

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Keywords

  • COMT polymorphism
  • Low back pain
  • migraine
  • morphine
  • response
  • triptans

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Neurology
  • Clinical Neurology

Cite this

Cargnin, S., Magnani, F., Viana, M., Tassorelli, C., Mittino, D., Cantello, R., Sances, G., Nappi, G., Canonico, P. L., Genazzani, A. A., Raffaeli, W., & Terrazzino, S. (2013). An opposite-direction modulation of the COMT val158met polymorphism on the clinical response to intrathecal morphine and triptans. Journal of Pain, 14(10), 1097-1106. https://doi.org/10.1016/j.jpain.2013.04.006