{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T10:03:11Z","timestamp":1780999391325,"version":"3.54.1"},"reference-count":38,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ilustre Colegio Profesional de Fisioterapeutas de la Comunidad de Madrid y el Colegio Oficial de Farmac\u00e9uticos de Madrid"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019s \u03bb = 0.917, F [4, 193] = 4.377, p = 0.002, n2p = 0.083, 1 \u2212 \u03b2 = 0.930) and lateral epicondyle (Wilk\u2019s \u03bb = 0.892, F [4, 193] = 5.870, p &lt; 0.001, n2p = 0.108, 1 \u2212 \u03b2 = 0.982), as well as CPT (Wilk\u2019s \u03bb = 0.872, F [4, 193] = 7.111, p &lt; 0.001, n2p = 0.128, 1 \u2212 \u03b2 = 0.995) or HPT (Wilk\u2019s \u03bb = 0.921, F [4, 193] = 4.133, p = 0.003, n2p = 0.079, \u03b2 \u2212 1 = 0.914), but not for the PPT at tibialis anterior (Wilk\u2019s \u03bb = 0.983, F [4, 193] = 0.834, p = 0.505, n2p = 0.017, 1 \u2212 \u03b2 = 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.<\/jats:p>","DOI":"10.3390\/ijms27115107","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T01:23:21Z","timestamp":1780622601000},"page":"5107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Influence of Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism in Conditioned Pain Modulation in Women with Migraine"],"prefix":"10.3390","volume":"27","author":[{"given":"Margarita","family":"Cigar\u00e1n-M\u00e9ndez","sequence":"first","affiliation":[{"name":"Department of Psychology, Universidad Rey Juan Carlos, 28922 Alcorc\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3087-3614","authenticated-orcid":false,"given":"Ana I.","family":"de-la-Llave-Rinc\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Universidad Rey Juan Carlos, 28922 Alcorc\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Pacho-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Research and Psychology in Education, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7539-2406","authenticated-orcid":false,"given":"Angela","family":"Tejera-Alonso","sequence":"additional","affiliation":[{"name":"Department of Psychology, Universidad Rey Juan Carlos, 28922 Alcorc\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6193-358X","authenticated-orcid":false,"given":"Cristina","family":"G\u00f3mez-Calero","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Universidad Rey Juan Carlos, 28922 Alcorc\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3772-9690","authenticated-orcid":false,"given":"C\u00e9sar","family":"Fern\u00e1ndez-de-las-Pe\u00f1as","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Universidad Rey Juan Carlos, 28922 Alcorc\u00f3n, Spain"},{"name":"Center for Neuroplasticity and Pain (CNAP), Sensory-Motor Interaction (SMI) Center, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, DK-9220 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0892-1579","authenticated-orcid":false,"given":"Lars","family":"Arendt-Nielsen","sequence":"additional","affiliation":[{"name":"Center for Neuroplasticity and Pain (CNAP), Sensory-Motor Interaction (SMI) Center, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, DK-9220 Aalborg, Denmark"},{"name":"Department of Gastroenterology & Hepatology, Mech-Sense, Clinical Institute, Aalborg University Hospital, DK-9000 Aalborg, Denmark"},{"name":"Steno Diabetes Center North Denmark, Clinical Institute, Aalborg University Hospital, DK-9000 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6755-8189","authenticated-orcid":false,"given":"Silvia","family":"Ambite-Quesada","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Universidad Rey Juan Carlos, 28922 Alcorc\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1186\/s10194-025-02142-9","article-title":"The global prevalence of headache disorders of public-health importance: A meta-analysis of population-based individual participant data from 41,614 adults from 17 countries","volume":"26","author":"Yu","year":"2025","journal-title":"J. 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