Pressure Pain Thresholds Across Nerve-Related and Muscular Sites in Frequent Episodic Tension-Type Headache: An Exploratory Case-Control Study.

Background/Objectives: Pressure pain thresholds (PPTs) are widely used to quantify hyperalgesia in tension-type headache (TTH). However, previous diagnostic accuracy research has mainly focused on muscular or segmental sites, while the discriminative performance of PPTs measured over peripheral nerves remains largely unexplored. This study primarily aimed to compare PPTs measured across nerve-related and muscular anatomical sites between women with frequent episodic TTH and headache-free controls. As a secondary exploratory objective, site-specific ROC analyses were performed to examine within-sample discrimination and derive sample-specific exploratory cut-offs. Methods: A cross-sectional exploratory study with a case-control sampling design evaluated 31 women with frequent episodic TTH (mean age: 19.6 ± 4.3 years) and 32 headache-free women (mean age: 22.1 ± 4.9 years). The groups differed significantly in age (p = 0.039). PPTs were recorded over peripheral nerves (greater occipital, median, ulnar, radial, tibial, common fibular), muscles (temporalis, tibialis anterior), 2nd-3rd interdigital hand space and the C5/C6 zygapophyseal joints. Results: Women with TTH showed lower PPTs than controls across all evaluated locations. However, after adjustment for age and Holm correction across the 20 anatomical sites, only the right greater occipital nerve remained statistically significant (p = 0.043). The right greater occipital nerve also yielded the highest area under the curve (AUC = 0.706; 95% CI 0.576-0.836) and was the only location whose AUC remained significantly different from 0.50 after correction for multiple testing (p = 0.040). Its sample-derived exploratory cut-off of 1.75 kg/cm2 showed low sensitivity (0.419; 95% CI 0.245-0.609) but high specificity (0.969; 95% CI 0.838-0.999). Although the corresponding LR+ was 13.419, its confidence interval was extremely wide (95% CI 1.866-96.525), indicating substantial imprecision. The LR- was 0.599 (95% CI 0.442-0.814). Overall, the operating characteristics varied considerably across locations and should be interpreted as exploratory. Conclusions: Women with frequent episodic TTH showed generally lower PPTs across nerve and muscle locations. However, after adjustment for age and multiple testing, the between-group difference was statistically supported only at the right greater occipital nerve. Although this location showed the highest AUC and high specificity at the sample-derived cut-off, its low sensitivity and the considerable imprecision of the LR+ estimate limit its interpretation. These findings reflect discrimination between selected participants with established TTH and headache-free controls, and should not be interpreted as evidence of clinical differential-diagnostic accuracy.