Central Sensitization May Occur in Cluster Headache

Woman with her head in her hands, migraine, headache
Woman with her head in her hands, migraine, headache
Individuals with vs without cluster headache were found to have lower cranial and extracranial pressure pain thresholds, indicating central sensitization.

Individuals with vs without cluster headache were found to have lower cranial and extracranial pressure pain thresholds (PPTs), indicating central sensitization, according to a study published in Pain Medicine.

Although central sensitization and its clinical markers — allodynia, hyperalgesia, and temporal summation (TS) — have been documented in some headache disorders and suggested as possible mechanisms in cluster headache, few studies have examined this hypothesis.

In this cross-sectional study, 20  adults with cluster headaches (60% and 40% with episodic and chronic headache, respectively; 55% with left-sided headache; median age, 37.5; 85% men; median disease duration, 14 years; median attack frequency, 1.5 per day; median pain intensity, 8/10; 70% taking preventive medications) and 16 healthy controls age 18 to 65 years (median age, 37; 81.3% men)with normal brain magnetic resonance imaging results were enrolled between September 2016 and June 2017.

Participants completed a general questionnaire regarding demographic and clinical information, as well as the Hospital Anxiety and Depression Scale (HADS), the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI), the 36-Item Short Form Health Survey (SF-36), the Headache Impact Test (HIT-6), and the Allodynia Symptom Checklist (ASC). Participants then underwent bilateral trigeminal and extra-trigeminal PPT and perceptual wind-up ratio testing to assess temporal summation of pain.

Participants with vs without cluster headache had lower PPTs at all locations (P <.001 at all points tested), but comparable wind-up ratios (P >.05). Regarding psychological factors, there were significant differences between patients with cluster headache and control participants on the HADS, BDI, STAI, SF-36, and ASC (P <.01 for all), as well as on the HIT-6 (P <.001).

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There was a moderate negative correlation in the control group between BDI and SF-36 (p =  −0.59; P =.03). In the cluster headache group, there was a strong positive correlation between HADS and attack duration (p = 0.86; P <.01), and between HADS and BDI (ρ = 0.75; P <.01). A moderate negative correlation was established between BDI and attack frequency (ρ = −0.52; P =.03), between SF-36 and HADS (ρ = −0.64; P =.03), between BDI and SF-36 (ρ = −0.53; P =.02), SF-36 and HIT-6 (ρ = −0.58; P <.01), and between attack intensity and PPT over symptomatic (ρ = −0.66; P <.01) and asymptomatic (ρ = −0.65; P <.01) supraorbital nerves.

Study limitations include the use of a non-validated ASC and the small sample size.

“The results obtained in previous studies evaluating central sensitization in patients with [cluster headache] coincide with the results of the present study, and they support the main hypothesis that confirms the presence of central sensitization in patients with [cluster headache],” noted the authors. “These findings increase our knowledge of [cluster headache] and emphasize the importance of a multidisciplinary approach to treating these patients.”

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Gil-Martínez A, Navarro-Fernández G, Mangas-Guijarro MÁ, Díaz-De-Terán J. Hyperalgesia and central sensitization signs in patients with cluster headache: a cross-sectional study. Pain Med. April 2019:1-9. doi:10.1093/pm/pnz070