Potential neural mechanisms of acupuncture therapy on migraine: a systematic review and activation likelihood estimation meta-analysis update.

Background: Migraine is a common, disabling, chronic headache disorder. Acupuncture is one of the effective complementary therapies for migraine. However, the neural mechanisms of acupuncture on migraine remain unclear. With the increased number of neuroimaging studies of acupuncture for migraine in recent years, there is an urgent need to update the data for pooled analyses. This study aimed to comprehensively summarize the relevant literature, identify brain regions with significant changes in brain activity after acupuncture, and explore the potential neural mechanisms of acupuncture on migraine.

Methods: A search was conducted by two independent researchers for neuroimaging studies using resting-state functional magnetic resonance imaging (fMRI) or positron emission tomography (PET) on the effects of acupuncture on migraine up to October 2023 in the databases of PubMed, MEDLINE, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data, Chinese Science and Technology Journal Database (VIP), and Chinese Biomedical Literature Database (SinoMed). Observational studies and clinical trials in Chinese or English were included; abstracts and studies without peer review were excluded. Brain regions with increased or decreased activity in the true acupuncture (TA) and sham acupuncture (SA) groups were pooled. A meta-analysis was performed using the activation likelihood estimation (ALE) algorithm. Fail-safe N (FSN) analysis was performed for publication bias and jackknife analysis was implemented for sensitivity analysis.

Results: The ALE meta-analysis included 15 peer-reviewed functional brain imaging studies with 514 migraine patients (401 female; mean age 32.38 years) and 163 healthy controls (130 female; mean age 27.28 years). A total of 12 studies scored 18 and above on the quality assessment (out of a total of 20). The results showed two increased activity clusters (the left pons and posterior insula) and four decreased activity clusters [the left cerebellum, temporal lobe, and right precuneus (two clusters)] after TA relative to baseline (P<0.001 uncorrected, volume >100 mm). We also identified five clusters of increased and seven clusters of decreased activity of SA relative to the baseline, and no overlap regions were found between the TA and SA groups (P<0.001 uncorrected, volume >100 mm). The results showed high replicability and reliability.

Conclusions: Acupuncture for migraine is a complex but targeted neuromodulation process, different from the random, nonspecific effects of SA. Emotional processing and sensitization reduction may be critical neurofunctional mechanisms of acupuncture. More high-quality randomized controlled studies are needed to validate the results.