Widespread Hypersensitivity to Pressure Pain in Men With Cluster Headache During Prolonged Remission Is Not Related to the Levels of Depression and Anxiety

Abstract

Background Diminished pressure pain thresholds (PPTs) have been found in patients with cluster headache (CH), suggesting the presence of central sensitization. However, it is not known whether sensitization persists over time during the asymptomatic periods. Objective To investigate if men with episodic CH in a long‐lasting remission phase exhibit widespread pressure pain hypersensitivity. Methods Forty men with episodic CH and 40 matched controls were enrolled. PPTs were assessed bilaterally over 1 trigeminal (temporalis muscle) and 3 extra‐trigeminal points (C5/C6 zygapophyseal joint, second metacarpal, tibialis anterior muscle) by a blinded assessor. Patients were assessed in a prolonged remission phase, at least 6 months after their last CH attack and without taking any medication. Depression and anxiety levels were assessed with the Hospital Anxiety and Depression Scale (HADS). For each point, differences in PPTs were evaluated with a multivariate mixed‐model analysis of covariance test, with side and group as main factors and depression and anxiety levels as covariates. Results PPTs were significantly decreased bilaterally over the temporalis muscle (mean difference: 85 to 100 kPa), C5/C6 zygapophyseal joint (mean difference: 65 to 80 kPa), second metacarpal (mean difference: 65 to 90 kPa), and tibialis anterior muscle (mean difference: 135 to 155 kPa) in patients with CH when compared to headache‐free subjects (all, P < 0.001). No effect of anxiety or depression levels was found. Conclusions Patients with CH exhibited bilateral widespread hypersensitivity to pressure pain during long‐lasting remission periods, which was not associated with depression or anxiety. These results support the persistence of central sensitization in episodic CH, even in remote asymptomatic phases.

Spatial Distribution of Temporalis Pressure Pain Sensitivity in Men with Episodic Cluster Headache

“…All patients had unilateral CH with no side shifts (19 left side, 21 right side). Table 1 summarizes clinical data of both groups [11].…”

“…The current paper is part of a multicenter headache study. Some of the patients of the current study were also included in a previous study [11]. This study presents new additional data and different statistical analyses.…”

“…A structured questionnaire was used to obtain demographic and clinical data, including [11] age, time since the onset of CH, number of clusters/year, time since the last cluster period, painful side in the last cluster attack and in previous attacks, intensity and duration of attacks, medication intake for attacks, and time without medication. All participants reported normal neurologic and ophthalmologic examinations as well as normal brain magnetic resonance imaging (MRI).…”

“…Participants attended a preliminary session for familiarization with pressure test procedures where PPT assessment was first made on the wrist extensor muscles of the right forearm. The assessments were held in an asymptomatic and remission phase, e.g., when no headache attack had occurred for at least 3 months to ensure that the patient was not switching to a chronic form of CH [11,12] and to avoid pain-related allodynia. Additionally, preventive medication or abortive drugs had to be stopped at least 1 month before PPT assessments.…”

“…As previously described [11], sample size was calculated for detecting a moderate-large effect size (0.70) between patients and controls on PPT, with a two-tailed test, an alpha level (α) of 0.05 and a desired power (β) of 90%. These data generated a sample size of at least 35 participants per group.…”