Background

Previously reported increases in serum levels of vasodilating neuropeptides pituitary adenylate cyclase-activating peptide-38 (PACAP38) and vasoactive intestinal peptide (VIP) during attacks of cluster headache could indicate their involvement in cluster headache attack initiation. We investigated the attack-inducing effects of PACAP38 and vasoactive intestinal peptide in cluster headache, hypothesising that PACAP38, but not vasoactive intestinal peptide, would induce cluster-like attacks in episodic active phase and chronic cluster headache patients.

Methods

In a double-blind crossover study, 14 episodic cluster headache patients in active phase, 15 episodic cluster headache patients in remission phase and 15 chronic cluster headache patients were randomly allocated to receive intravenous infusion of PACAP38 (10 pmol/kg/min) or vasoactive intestinal peptide (8 pmol/kg/min) over 20 min on two study days separated by at least 7 days. We recorded headache intensity, incidence of cluster-like attacks, cranial autonomic symptoms and vital signs using a questionnaire (0–90 min).

Results

In episodic cluster headache active phase, PACAP38 induced cluster-like attacks in 6/14 patients and vasoactive intestinal peptide induced cluster-like attacks in 5/14 patients (p = 1.000). In chronic cluster headache, PACAP38 and vasoactive intestinal peptide both induced cluster-like attacks in 7/15 patients (p = 0.765). In episodic cluster headache remission phase, neither PACAP38 nor vasoactive intestinal peptide induced cluster-like attacks.

Conclusions

Contrary to our hypothesis, attack induction was lower than expected and roughly equal by PACAP38 and vasoactive intestinal peptide in episodic active phase and chronic cluster headache patients, which contradicts the PAC₁-receptor as being solely responsible for attack induction.

Trial registration: clinicaltrials.gov (identifier NCT03814226).

中文翻译：

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垂体腺苷酸环化酶激活肽 38 和血管活性肠肽在丛集性头痛中的作用。

背景

先前报道的在丛集性头痛发作期间血管舒张神经肽垂体腺苷酸环化酶激活肽 38 (PACAP38) 和血管活性肠肽 (VIP) 的血清水平升高可能表明它们参与了丛集性头痛发作的开始。我们研究了 PACAP38 和血管活性肠肽在丛集性头痛中的诱发发作作用，假设 PACAP38 而非血管活性肠肽会在发作性活动期和慢性丛集性头痛患者中诱发丛集样发作。

方法

在一项双盲交叉研究中，14 名处于活动期的发作性丛集性头痛患者、15 名处于缓解期的发作性丛集性头痛患者和 15 名慢性丛集性头痛患者被随机分配接受静脉输注 PACAP38（10 pmol/kg/min）或血管活性药物肠肽 (8 pmol/kg/min) 在至少相隔 7 天的两个研究日超过 20 分钟。我们使用问卷（0-90 分钟）记录了头痛强度、集群样发作的发生率、颅自主神经症状和生命体征。

结果

在发作性丛集性头痛活动期，PACAP38 在 6/14 患者中诱发丛集样发作，在 5/14 患者中血管活性肠肽诱发丛集样发作 ( p  = 1.000)。在慢性丛集性头痛中，PACAP38 和血管活性肠肽均在 7/15 的患者中引起丛集样发作（p  = 0.765）。在发作性丛集性头痛缓解期，PACAP38 和血管活性肠肽均未诱导丛集样发作。

结论

与我们的假设相反，在发作性活动期和慢性丛集性头痛患者中，PACAP38 和血管活性肠肽的攻击诱导低于预期且大致相等，这与 PAC ₁受体仅负责攻击诱导相矛盾。

试验注册： clinicaltrials.gov（标识符 NCT03814226）。