Polymorphisms of the Proinflammatory Cytokine Genes Modulate the Response to NSAIDs but Not to Triptans in Migraine Attacks

Int J Mol Sci. 2022 Dec 30;24(1):657. doi: 10.3390/ijms24010657.

Abstract

Migraine is a common neurovascular disorder characterized by recurrent episodes of headache and associated neurological symptoms. At present, a significant portion of patients do not obtain a satisfactory response to acute pain-relieving therapies, including NSAIDs and triptans. In this context, pharmacogenetics plays a key role in the understanding of such a diverse response. In order to investigate whether functional polymorphisms in proinflammatory cytokine genes (IL-1α, IL-1β, IL-1RN; IL-6 and TNF-α) may influence the response to acute treatment, 313 consecutive patients with episodic migraine without aura were enrolled. Pain relief by administration of NSAIDs or triptans for three consecutive migraine attacks was evaluated. We found a significant association between A allele of the TNF-α promoter (−308 A/G) and a lack of efficacy after NSAID administration (p < 0.01, OR 2.51, 95% CI: 1.33 < OR < 4.75 compared to the G allele). Remaining polymorphisms had no significant effect on pain relief. Our study showed that a functional polymorphism in the TNF-α gene significantly modulates the clinical response to NSAID administration in acute attacks. Patients with higher production of the active cytokine during stress showed a significantly lower anti-migraine effect. Our results further support a role for TNF-α in the pathophysiological mechanisms of migraine attack.

Keywords: NSAIDs; TNF-α; cytokines; migraine; polymorphism; triptans.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal* / therapeutic use
  • Headache / drug therapy
  • Humans
  • Migraine Disorders* / drug therapy
  • Migraine Disorders* / genetics
  • Tryptamines* / therapeutic use
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Tryptamines
  • Tumor Necrosis Factor-alpha

Grants and funding

This study was supported by Ministero dell’Università e della Ricerca, and MUR project “Dipartimenti di Eccellenza 2018 e 2022” to the Department of Neurosciences “Rita Levi Montalcini”, University of Torino, Italy.