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

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.

Study on the correlation between IL-12p70, IL-17A and migraine in children

“…Unfortunately, no significant predictive value for diagnosis was found. However, Rubino et al firstly used pharmacogenetic methods to confirm that TNF-α polymorphisms in gene function significantly modulated the clinical response to NSAID administration during acute migraine attacks, further supporting the role of the pro-inflammatory cytokine TNF-α in the pathophysiological mechanism of migraine attack ( 11 ).…”

Experimental and Clinical Investigation of Cytokines in Migraine: A Narrative Review

“…Genetic analysis of cytokines suggests that TNF-α and other cytokines are involved not only in the risk of migraine [104][105][106]119] but also in the pathophysiology during attacks [111]. Furthermore, comprehensive genetic analysis using GWAS has identified not only genes encoding CGRP and 5-HT1F receptors but also genes involved in the production of TNF-α and IL-6 and regulating apoptosis and inflammatory responses as candidate genes for migraine [115,116].…”

“…An analysis of sites in linkage disequilibrium with variants including rs1800629 aimed at resolving previously reported discrepancies and showed that the LTA gene haplotype was associated with migraine risk in Koreans [110]. In addition, pharmacogenetics showed that the efficacy of NSAIDs was significantly lower in migraine attacks in rs1800629 carriers [111], suggesting that rs1800629 may be deeply involved in the pathophysiology of migraine attacks as well as in the risk of migraine. The reproducibility of the results is expected to be reported.…”