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Catechol-O-Methyltransferase (COMT) rs4680Val158Met Polymorphism is Associated With Widespread Pressure Pain Sensitivity and Depression in Women With Chronic, but not Episodic, Tension-Type Headache

Fernández-de-las-Peñas, César, PT, PhD, DrMedSci*,†; Ambite-Quesada, Silvia, PT, PhD*,†; Palacios-Ceña, María, PT, PhD*,†; Guillem-Mesado, Amparo, MD; Guerrero-Peral, Ángel, MD, PhD§; Pareja, Juan A., MD, PhD; Arendt-Nielsen, Lars, PhD, DrMedSci

doi: 10.1097/AJP.0000000000000684
Original Articles

Objectives: The aims of this study were: (1) to investigate the association between the rs4680Val158Met polymorphism in frequent episodic tension-type headache (FETTH) and chronic tension-type headache (CTTH); and (2) to analyze the association between the rs4680Val158Met polymorphism with clinical, psychological, or psychophysical variables.

Methods: In total, 50 women with FETTH, 50 with CTTH, and 50 matched headache-free women participated. After amplifying Val158Met polymorphism by polymerase chain reaction, the genotype frequencies and allele distributions based on restriction fragment length polymorphism were assessed. Participants were classified according to the Val158Met polymorphismrs4680 genotype (Val/Val, Val/Met, or Met/Met). A headache diary collected clinical features. Disability (Headache Disability Inventory), sleep quality (Pittsburgh Sleep Quality Index), and depression/anxiety levels (Hospital Anxiety and Depression Scale) were also assessed. Pressure pain thresholds were assessed bilaterally over the temporalis, upper trapezius, second metacarpal, and tibialis anterior by a blinded assessor.

Results: The distribution of rs4680 Val158Met genotype was not significantly different between women with/without headache (P=0.796). No differences in headache features, disability, anxiety, or sleep quality were observed depending on the rs4680 Val158Met genotype. Women with CTTH, but not FETTH, carrying the Met/Met genotype had lower widespread pressure pain thresholds and higher depressive symptoms than those with Val/Val or Val/Met genotype (P<0.05).

Conclusions: The Val158Met polymorphism (rs4680) does not appear to be involved in predisposition to tension-type headache; however, this genetic factor may be involved in the pathogenesis expression of CTTH, as greater pressure pain sensitivity and higher depressive levels were found in CTTH carrying the Met/Met genotype.

*Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, Alcorcón

Department of Neurology, Hospital Universitario Gregorio Marañón

Department of Neurology, Hospital Universitario Fundación Alcorcon, Madrid

§Headache Unit, Hospital Clínico Universitario de Valladolid, Valladolid, Spain

Department of Health Science and Technology, School of Medicine, Center for Sensory-Motor Interaction (SMI), Aalborg University, Aalborg, Denmark

C.F.-d.-l.-P., S.A.-Q., and M.P.C.: did the main analysis and interpretation of data. A.G.-M., Á.G.-P., J.A.P. and L.A.-N.: provided administrative, technical, and material support. L.A.-N.: supervised the study.

The authors declare no conflict of interest.

Reprints: César Fernández-de-las-Peñas, PT, PhD, DrMedSci, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avenida de Atenas s/n, Alcorcón, Madrid 28922, Spain (e-mail:

Received October 1, 2018

Received in revised form December 12, 2018

Accepted December 19, 2018

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