ABSTRACT:Our aim was to investigate the relationship between Val158Met polymorphisms, headache, and pressure hypersensitivity in children with chronic tension-type headache (CTTH). A casecontrol study with blinded assessor was conducted. Seventy children with CTTH associated with pericranial tenderness and 70 healthy children participated. After amplifying Val158Met polymorphism by polymerase chain reactions, we assessed genotype frequencies and allele distributions. We classified children according to their T ension-type headache is the most common form of head pain in both adult (1) and child (2) population. Although there has been an increasing knowledge in the pathogenesis of tension-type headache (TTH), the pathoanatomical mechanisms are not completely understood (3). As TTH has several negative repercussions for children, further studies are needed (4,5).Genetic epidemiological studies have investigated the familial aggregation of TTH. In fact, in individuals with chronic TTH (CTTH), first-degree relatives have a 3.1-fold significantly increased risk of suffered from CTTH (6,7), suggesting a possible role of genetic factors in CTTH. The catechol-Omethyltransferase (COMT) gene is one of the several potential headache genetic determinants. The COMT is an enzyme involved in the metabolic degradation of dopamine, norepinephrin, and epinephrine (8). Several studies indicate that the genetic polymorphism due to a G3 A substitution at codon 158 of the COMT gene, which leads to a valine (Val) to methionine (Met) substitution, results in differences in COMT activity: a valine (Val) at codon 158 results in a heat-stable, high-activity COMT variant (Val/Val), whereas a methionine (Met) at this position (Val/Met, or Met/Met) results in heatlabile, low-activity variants (9,10). Zubieta et al. (11) demonstrated that individuals with Val/Val genotype have a 3-to 4-fold higher activity of the COMT enzyme and reduced pain sensitivity compared with those with the Met/Met genotype, suggesting that the presence of Met/Met genotype may predispose for chronic pain.Although it might be possibly an influence of COMT polymorphisms for chronic pain, few studies have examined the association between Val158Met polymorphisms and headache. In addition, results from the studies are controversial, as one study found that the frequency of Met/Met genotype was higher in subjects with migraine (12), whereas others reported no differences in genotype distribution and allele frequency of COMT polymorphisms between migraine and healthy subjects (13,14). Another study did not find relationship of Val158Met polymorphism at the COMT in individuals with medication overuse chronic daily headache, episodic migraine without aura, and without analgesic abuse and healthy controls (15). Therefore, more studies are required.In addition, mechanical hypersensitivity is considered a clear manifestation of hyperexcitability of peripheral and central nociceptive pain pathways in TTH, in both adults (16) and children (17). Jensen et al. (18) have recently rep...