Cranial autonomic symptoms in migraine are related to central sensitization: a prospective study of 164 migraine patients at a tertiary headache center

Abstract

Background Cranial autonomic symptoms (CASs) during migraine attacks are reported to be quite common regardless of ethnicity. In our previous study investigating 373 migraineurs, we found that 42.4% of them had CASs. The patients with CASs more frequently had cutaneous allodynia than did those without CASs, and we speculated that CASs were associated with central sensitization. The present study searched for substantial evidence on the relationship between CASs and central sensitization in migraine patients. Methods This was a prospective cross-sectional study. We studied a new independent cohort of 164 migraineurs who presented to the Tominaga Hospital Headache Center from July 2018 until December 2019. The clinical features of CASs according to the criteria in ICHD-3 (beta) were investigated. We also evaluated central sensitization based on the 25 health-related symptoms utilizing the validated central sensitization inventory (CSI), and each symptom was rated from 0 to 4 resulting a total score of 0–100. Results The mean age was 41.8 (range: 20 to 77) years old. One hundred and thirty-one patients (78.9%) were women. Eighty-six of the 164 (52.4%) patients had at least 1 cranial autonomic symptom. The CSI score of the patients with ≥3 CASs reflected a moderate severity and was significantly higher than in those without CASs (41.9 vs. 30.7, p = 0.0005). The score of the patients with ≥1 conspicuous CAS also reflected a moderate severity and was significantly higher than in those without CASs (40.7 vs. 33.2, p = 0.013). The patients in the CSI ≥40 group had lacrimation, aural fullness, nasal blockage, and rhinorrhea, which are cranial autonomic parasympathetic symptoms, significantly more frequently than those in the CSI < 40 group. Conclusions Migraine patients with CASs showed significantly greater central sensitization than those without such symptoms. In particular, cranial parasympathetic symptoms were more frequent in centrally sensitized patients than in nonsensitized patients, suggesting that cranial parasympathetic activation may contribute to the maintenance of central sensitization. Trial registration This study was retrospectively registered with UMIN-CTR on 29 Aug 2020 (UMIN000041603).

Cranial Autonomic Symptoms and Migraine: What Relationship and What Meaning? A Review

“…These data [7,28] confirmes those coming from the clinical series [4][5][6][8][9][10][11][12][13][14][15][17][18][19][20][21][22][23][24][25][26][27]. Further the prevalence may be sometimes undervalued because some researches only look for the unilateral CAS while in clinical series they may be also present bilaterally as well as migraine pain may have bilateral lateralization.…”

“…Another study [27] evidenced that CAS+ migraineurs had significantly a greater central sensitization scored by the validated central sensitization inventory (CSI), suggesting a role of cranial parasympathetic activation to activate the central sensitization. This study support the Yarnitsky et al [38] study that suggested that the role of cranial parasympathetic outflow to sensitize the intracranial nociceptors and to induce parasympathetically indipendent allodynia by sensitizing central trigeminal nociceptors.…”

Central Sensitization in Migraine: A Narrative Review

“…The determinants of CS in migraine patients were restless legs syndrome and interference of headache pain with daily activities. Danno et al, 54 (2022) 164 patients with migraine A cross-sectional study using CSI CS was observed in 32.3% of migraine patients and was related to cranial parasympathetic symptoms such as lacrimation, aural fullness, nasal blockage, and rhinorrhea, Suzuki et al, 56 (2022) 95 patients with migraine A cross-sectional study using CSI and QEESI Multiple chemical sensitivity was found in 20% of migraine patients and was related to CS, photophobia, osmophobia, visual aura, sensory aura, higher migraine-related disability and Kessler Psychological Distress scores. Note : CSI scores ≥ 40 were defined as having CS.…”

“…For example, in a cross-sectional study including 164 patients with migraine, CS was observed in 53 patients (32.3%). 54 CS is associated with cranial parasympathetic symptoms such as lacrimation, aural fullness, nasal blockage, and rhinorrhea, suggesting that both trigeminovascular systems and the cranial parasympathetic system contribute to persistent CS in patients with migraine. MCS is reported to overlap with fibromyalgia, a disease known to be associated with CS.…”

Pathophysiology and Therapy of Associated Features of Migraine

“…Many of these “evahistic” manifestations can actually be the main symptom of the clinical picture in a patient with migraine, and imply a higher disability [ 5 ]. Migraine patients with sensory hypersensitivity may have more attention difficulties during daily activities [ 6 ], or more cranial autonomic symptoms associated to the headache [ 7 ], and the response to preventive treatments may vary [ 8 ]. Exogenous factors, such as stress, obesity, intestinal microbiota and even parental behaviour, have been speculated to play a role in the chronification and sensitization process [ 9 , 10 , 11 , 12 ].…”