Influence of Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism in Conditioned Pain Modulation in Women with Migraine.

The role of the catechol-O-methyltransferase (COMT) Val158Met rs4680 polymorphism in altered pain processing in headaches is controversial. The aim of this study was to investigate the influence of the Val158Met rs4680 polymorphism in conditioned pain modulation (CPM) in women with migraine. A case-control study including 70 women with chronic migraine, 70 with episodic migraine and 70 pain-free women was conducted. Pressure pain thresholds (PPTs) at the temporalis muscle, lateral epicondyle, and tibialis anterior were bilaterally assessed. Heat (HPT) and cold (CPT) pain thresholds at the frontalis muscle were also assessed. Subsequently, CPM was evaluated immediately after a one-minute cold-pressor test paradigm on changes obtained in PPTs, HPT and CPT. Thus, after amplifying Val158Met polymorphism by polymerase chain reaction, genotype frequencies (Val/Val, Val/Met, or Met/Met) and allele distributions were identified. The distribution of Val158Met genotypes (p = 0.097) was not significantly different among women with episodic migraine, chronic migraine and pain-free controls. The results revealed significant group*time*Val 158Met interactions for PPTs at the temporalis (Wilk's λ = 0.917, F [4, 193] = 4.377, p = 0.002, n2p = 0.083, 1 - β = 0.930) and lateral epicondyle (Wilk's λ = 0.892, F [4, 193] = 5.870, p < 0.001, n2p = 0.108, 1 - β = 0.982), as well as CPT (Wilk's λ = 0.872, F [4, 193] = 7.111, p < 0.001, n2p = 0.128, 1 - β = 0.995) or HPT (Wilk's λ = 0.921, F [4, 193] = 4.133, p = 0.003, n2p = 0.079, β - 1 = 0.914), but not for the PPT at tibialis anterior (Wilk's λ = 0.983, F [4, 193] = 0.834, p = 0.505, n2p = 0.017, 1 - β = 0.263). Women with chronic migraine with the Met/Met genotype exhibited reduced CPM indexes for PPT, CPT, or HPT at the temporalis (trigeminal area) than those with the Val/Val genotype. This study showed that CPM deficit is higher in women with migraine with the Met/Met genotype, but this association is mostly present in the symptomatic (trigeminal) area in the chronic form of the disease. No association of the Met/Met genotype with CPM was seen in healthy controls.