Effectiveness of Peripheral Nerve Blocks for the Treatment of Primary Headache Disorders: A Systematic Review and Meta-Analysis

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Written By Dr. Marcus Yu Bin Pai

MD, PhD. Physical Medicine & Rehabilitation Physician from São Paulo - Brazil. Pain Fellowship in University of São Paulo.

Effectiveness of Peripheral Nerve Blocks for the Treatment of Primary Headache Disorders: A Systematic Review and Meta-Analysis

Headaches, especially migraine and tension-type headaches, are extremely common disorders affecting a large proportion of the population globally.

They cause substantial disability and negatively impact quality of life. In emergency departments (EDs), acute headache treatment poses challenges due to the slow onset of pain relief from standard medications like NSAIDs, triptans, and dopamine antagonists. This systematic review and meta-analysis examined the effectiveness of peripheral nerve blocks, including greater occipital nerve blocks, sphenopalatine ganglion blocks, and trigger point injections, as potential faster treatment options for primary headache disorders in the ED or clinic setting.


This was a systematic review and meta-analysis of randomized controlled trials comparing peripheral nerve blocks to placebo or active control for treatment of primary headache disorders. A comprehensive literature search was conducted in November 2020 using Ovid MEDLINE, EMBASE, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials. Eligible studies were randomized trials of patients with migraine, tension, or benign primary headaches receiving peripheral nerve blocks. Outcomes collected were pain scores at multiple timepoints up to 2 hours. Meta-analyses using a random effects model were conducted when studies were sufficiently homogenous. The certainty of evidence was assessed using GRADE criteria.


11 randomized trials (N=860 patients) met eligibility criteria, with 9 included in meta-analyses. Compared to placebo, peripheral nerve blocks significantly reduced pain scores at 1, 5, 15 and 30 minutes. At 15 minutes, the mean difference in pain scores was -1.17 (95% CI -1.82 to -0.51, p=0.0005, I2=49%).

At 30 minutes, the mean difference was -0.99 (95% CI -1.66 to -0.32, p=0.004, I2=36%). Peripheral nerve blocks were associated with minor adverse events like burning sensation or numbness, but no serious adverse events. Evidence for other secondary outcomes was limited and inconsistent.

Primary Outcome – Pain Scores Within 120 Minutes

  • For the comparison of peripheral nerve blocks versus placebo, 9 randomized controlled trials were included in the meta-analysis.
  • Peripheral nerve blocks significantly reduced pain scores compared to placebo at very early time points. At 1 minute, the mean difference in pain scores was -0.92 (95% CI -1.38 to -0.46, I2=23%).
  • The pain relieving effects compared to placebo increased over time. At 5 minutes, the mean difference was -1.05 (95% CI -1.67 to -0.43, I2=55%).
  • The maximal differences were observed at 15 minutes, with a mean reduction of -1.17 (95% CI -1.82 to -0.51, I2=49%) favoring peripheral nerve blocks.
  • This statistically significant pain relief was maintained at 30 minutes, with a mean difference of -0.99 (95% CI -1.66 to -0.32, I2=36%).
  • Only 2 studies assessed pain at 45 and 60 minutes. The limited data showed dissipation of the treatment effect by 45-60 minutes.
  • Peripheral nerve blocks appeared beneficial for pain management versus placebo within the first 30 minutes based on this meta-analysis.

Secondary Outcomes:

  • Adverse events were more common with peripheral nerve blocks, but were mild (e.g. burning sensation, numbness). No serious adverse events were reported.
  • Evidence around need for rescue medications was limited and inconsistent between studies.
  • Only 2 studies measured return ED visits for headache within 72 hours. Results were conflicting, preventing firm conclusions.
  • For the comparison to active treatment, there was insufficient data to pool studies for meta-analysis due to clinical and methodological heterogeneity. Peripheral nerve blocks appeared favorable at earlier timepoints based on limited data.


This systematic review found evidence that peripheral nerve blocks can provide rapid pain relief within 30 minutes for primary headache disorders compared to placebo. However, there was insufficient evidence to determine effectiveness compared to standard active treatments.

Peripheral nerve blocks, especially sphenopalatine ganglion blocks, should be considered as adjunctive therapy for acute headache management in the ED.

Comparison with standard treatment options

High-quality randomized controlled trials are needed that directly compare specific peripheral nerve block techniques head-to-head with standard abortive treatments like triptans, dopamine antagonists, NSAIDs, or opioids.

Studies should have larger sample sizes, blinding, concealed allocation, validated headache diagnosis criteria, standardization of nerve block protocols, and assessment of pain at serial clinically relevant time points. This will provide evidence to determine if nerve blocks are truly superior or at least non-inferior to current first-line medications for acute headache treatment in the ED setting.

Optimal techniques and dosing

There is heterogeneity in the peripheral nerve block techniques and anesthetic dosing used across studies. Some evidence suggests shorter-acting lidocaine provides faster onset of pain relief compared to longer-acting bupivacaine.

However, bupivacaine may confer greater duration of analgesia. Optimal dosing has not been firmly established. Future studies comparing different anesthetic agents and doses head-to-head while measuring both speed of onset and duration of effects would help refine the protocols.

Further high quality research is needed to establish peripheral nerve blocks as first-line alternatives to standard therapies.


Peripheral nerve blocks reduce pain scores within 30 minutes versus placebo for primary headaches, but more evidence is required to demonstrate superiority or non-inferiority over standard active treatments.

They are a safe and rapid option to consider as adjunctive therapy for acute headache in the ED.


Patel D, Yadav K, Taljaard M, Shorr R, Perry JJ. Effectiveness of peripheral nerve blocks for the treatment of primary headache disorders: A systematic review and meta-analysis. Annals of Emergency Medicine. 2022 Mar 1;79(3):251-61.

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MD, PhD. Physical Medicine & Rehabilitation Physician from São Paulo - Brazil. Pain Fellowship in University of São Paulo.

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