Serotonergic Activity Contributes to Analgesic Overuse in Chronic Tension‐Type Headache

Abstract

To evaluate the possible existence of a genetically determined innate factor that could exert a profound influence on the development of analgesic overuse in chronic tension-type headache (CTTH). Many patients with CTTHs report the regular use of analgesics. Continuous use of analgesics results in the ultimate worsening of headaches. The factors related to development of analgesic overuse, however, remain poorly understood. The genetic factors for serotonin metabolism and the harm avoidance (HA) personality dimension are known to be associated with various substance abuse patterns. We performed serotonin transporter protein (5-HTT) gene-linked polymorphic region (5-HTTLPR) genotype polymorphism analyses, and investigated serotonin-related personality traits by assessing the HA dimension using tridimensional personality questionnaire, given to 48 patients with CTTHs and reported analgesic overuse (CTTH-AO), in 50 patients with CTTHs without analgesic overuse (CTTH-NO), and in 100 healthy controls. We compared their headache characteristics using standardized questionnaires. We discovered an excess frequency of 5-HTTLPR short allele and a different genotypic distribution in patients with CTTH-AO. The S/S genotype frequency was significantly higher in patients with CTTH-AO (83%) than in CTTH-NO (72%) and control (59%; P= .010) groups. Patients with CTTH-AO exhibited the highest HA scores (23.3 +/- 5.4), as compared to CTTH-NO (19.9 +/- 6.7) and control (16.3 +/- 6.1) groups. Individuals with the S/S genotype showed a greater tendency toward analgesic overuse (13.3 +/- 11.3 days per month) than did those with the non-S/S genotype (7.0 +/- 8.6 days per month: P= .02). Our data suggest that serotonergic activity may be involved in the development of analgesic overuse in CTTH and that 5-HTTLPR might be one of the genetically contributing factors.