Peripheral nerve blocks in primary headaches and neuralgias: a six-country multicenter real-world study

Peripheral nerve blocks (PNBs) represent an accessible, minimally invasive therapeutic approach for headache disorders; however, real-world data on procedural patterns and outcomes in different headache subtypes remain limited. This multicenter study evaluated 2,219 patients (receiving 2250 PNBs) with migraine, tension-type headache (TTH), trigeminal autonomic cephalalgias (TACs), and cranial neuralgias. Demographic features, preventive and acute medicine, target nerves, anaesthetic agents, injection volumes, application intervals, number of sessions, clinical outcomes, and adverse events were analysed. Longitudinal outcomes were assessed with three-level mixed-effects models accounting for repeated visits within patients and patients within centers, using linear mixed models for VAS and cumulative-link mixed models for ordinal headache frequency and analgesic use. Migraine was the predominant diagnosis (77.5%), comprising chronic (55.6%) and episodic (44.4%) forms. Greater occipital nerve block was the dominant procedure in migraine, TTH, and TACs, but was less frequent in neuralgias, both in occipital and trigeminal. Injection volume, application interval, and local anesthetic choice varied by headache type and target nerve. GON volumes were most often 1-2 mL across headache groups, except in neuralgias, where 2-3 mL was most common. PNBs were associated with statistically significant improvements in headache frequency, severity, and duration as well as decrease in analgesic use in all analysed groups and subgroups. Adverse events were uncommon and mainly mild. Intercept-only models indicated modest center-level clustering, with ICCs of 0.093 for VAS scores, 0.134 for headache frequency, and 0.130 for analgesic use. Overall, these findings support PNBs as useful and well-tolerated options while highlighting substantial real-world variation in practice.