Peripheral nerve blocks, steroid injections and their niche in headache medicine.

Peripheral nerve blocks (PNBs) have long been employed in the treatment of various primary and secondary headache disorders (1), are increasingly used in general neurological practice (2) and may be utilized by up to 69% of practitioners with expertise in the treatment of headache disorders (3). The mechanism for PNBs in the treatment of headache disorders is not known. Clearly, the treatment effect is not based on a pure peripheral action. This principle is best demonstrated by the highest quality of evidence for PNBs in the treatment of cluster headache. A single (4,5) or repeated (6) injection with corticosteroid in the occipital or suboccipital region, targeting the greater occipital nerve (GON), derived largely from the C2 spinal level, effectively treats cluster headache, which is a trigeminal autonomic cephalalgia featuring pain in the ophthalmic division of the trigeminal nerve. In addition, pain relief from PNBs may not depend on the presence or duration of a pure local anesthetic effect (5), also evident by their reduction in allodynia contralateral to the side of injection (7) as well as photophobia (8). Presumably, GON blocks and other PNBs reduce nociceptive input into the trigeminocervical complex and lead to central descending inhibitory, secondary effects (8) in aborting an acute headache attack or shortening an acute cluster period. There is a wealth of clinical experience and a heterogeneous evidence base suggesting PNBs as a safe and effective therapy in headache medicine, particularly cluster headache (1,3,9). However, for migraine the evidence is less certain (1,9), most notably featuring a single randomized controlled comparative trial that assessed the benefit of a corticosteroid added to a local anesthetic agent in patients with transformed migraine (10). In this issue of Cephalalgia, Dilli and colleagues fill this gap, addressing GON blockade with corticosteroid for the treatment of migraine in a randomized, doubleblind, placebo-controlled trial (11). They included patients at a single center, 18–75 years of age with episodic or chronic migraine who had at least one weekly attack but without continuous headache, recent initiation of evidence-based prophylaxis, frequent opioid use, substance abuse, allergy to injection ingredients, major psychiatric disorder or other contemporaneous headache disorders. Patients were randomized to injections in the GON region with either the active therapy: 2.5ml 0.5% bupivacaine plus 0.5ml 20mg methylprednisolone or what they termed their placebo: 2.75ml normal saline plus 0.25ml 1% lidocaine without epinephrine. Injections were performed unilaterally or bilaterally, depending on the location of the patient’s head pain. Various baseline predictive data points were captured that are novel in this setting, including pain directionality and graded GON region tenderness. Prospective diary completion in the 4 weeks before and after GON blockade was another major strength. Reasonably based on their clinical experience, the primary endpoint was defined as a 50% or more reduction in the frequency of moderate or severe headache days in the active versus placebo group at 4 weeks compared to a 4 week preinjection baseline period. Ultimately the authors analyzed 33 patients in the active group and 30 patients in the placebo group, who were mostly women, usually featured an occipital location of head pain and had a mean baseline headache frequency of 13 days during the 4-week baseline period. Over 75% of patients in both groups received bilateral injections. The study failed to meet its primary endpoint, as the 50% reduction in the frequency of moderate or severe migraine headache days at 4 weeks was 30% for both groups. The study also failed to meet any secondary