Hyperalgesia and Central Sensitization Signs in Patients with Cluster Headache: A Cross-Sectional Study

Abstract

Objective To investigate central sensitization (CS) in cluster headache (CH) and to evaluate its relationship with disease characteristics and psychological comorbidities. Design Cross-sectional study. Settings Whether CS occurs in CH, as it does in other primary headaches, is a subject of debate. Few studies have evaluated the presence of CS and its relationship with psychological comorbidities in patients with CH. Subjects Twenty patients with episodic or chronic CH and 16 healthy controls were recruited. Methods The variables evaluated included frequency, intensity and duration of headache attacks, pressure pain thresholds (PPTs) and wind-up (WU) ratios of pain bilaterally measured over trigeminal and extratrigeminal areas, and results of questionnaires regarding anxiety and depression (Hospital Anxiety and Depression Scale [HADS], Beck Depression Inventory [BDI], State-Trait Anxiety Inventory [STAI]), quality of life (Short Form-36 [SF-36]), headache impact (Headache Impact Test [HIT-6]), and allodynia (Allodynia Symptom Checklist [ASC]). Results PPT levels were significantly lower in the CH group compared with the healthy participants (all tested points, P < 0.001). No differences were found in WU ratios between groups. However, differences in HADS (P < 0.01), BDI (P < 0.01), STAI (P < 0.01), SF-36 (P < 0.01), HIT-6 (P < 0.001), and ASC (P < 0.01) were observed between groups. The healthy group showed a moderate negative correlation between SF-36 and BDI (rho = –0.59, P = 0.03). Likewise, the CH group showed a moderate negative correlation between frequency and BDI (rho = –0.52, P = 0.03), a strong positive correlation between duration and HADS (rho = 0.86, P < 0.01), and a moderate negative correlation between intensity and PPT over symptomatic V1 (rho = –0.66, P < 0.01) and over asymptomatic V1 (rho = –0.65, P < 0.01). The CH group also showed a moderate negative correlation between SF-36 and anxiety and depression variables. Conclusions Our findings show that patients with CH have lower PPT levels at cranial and extracranial points, suggesting, as in other primary headaches, the presence of CS. We have also found a high prevalence of psychiatric comorbidities that correlate with the length and frequency of attacks. These findings highlight the importance of a multidisciplinary approach to the treatment of patients with CH.

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

“…Recent reviews have reported that PPTs are consistently lower in patients with migraine or tension‐type headache when compared with asymptomatic healthy subjects, with the trigemino‐cervical region being the most sensitive area . Our findings supporting the presence of widespread pain hyperalgesia and central sensitization in individuals with CH agree with those of Ladda et al, Fernández‐de‐las‐Peñas et al, and Gil‐Martínez et al However, these studies included small samples (ranging from 16 to 20) and did not control for the presence of depressive and anxiety levels, which could modify the excitability of central pain pathways . In fact, our study is the first one investigating widespread pressure pain hyperalgesia in individuals with CH that controlled for the potential effects of depression and anxiety, and is also the one with the largest sample to date.…”

“…Fernández‐de‐las‐Peñas et al also observed pressure pain hypersensitivity in both symptomatic and distant pain‐free areas in 16 men with episodic CH during a remission phase compared to controls. More recently, Gil‐Martínez et al found hypersensitivity to pressure pain at cranial and extra‐cranial points in 20 patients with episodic or chronic CH. The results of these studies all support the presence of widespread pressure pain hyperalgesia in CH.…”

“…Nevertheless, these studies included small sample sizes ranging from 16 to 20 subjects, and some of them also had heterogeneous samples that included patients of both genders, with either episodic or chronic CH and in different phases of the disease (active cluster or remission). Moreover, none of these studies has controlled the results of pain thresholds for the presence of mood disorders (eg, anxiety or depression) . Louter et al found that patients with CH have a 3‐fold increased risk for experiencing depression.…”

“…Moreover, none of these studies has controlled the results of pain thresholds for the presence of mood disorders (eg, anxiety or depression). [9][10][11] Louter et al 12 found that patients with CH have a 3-fold increased risk for experiencing depression. Since depression and anxiety may elicit different responses to the central nervous system, 13,14 studies assessing widespread pressure pain sensitivity should take into account these variables to confirm the presence of a genuine altered central nociceptive pain processing in individuals with CH.…”

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

“…There is also evidence showing the presence of pressure pain hypersensitivity over the trigeminal area in patients with CH. Yet, some authors have reported bilateral hypersensitivity to pressure pain [4,5], whereas others have described an asymmetry whereby the symptomatic side was more sensitive than the non-symptomatic side [6]. In all these studies, measurements were conducted on specific points in each of the head regions studied [4,5,6].…”