Therapeutic applications and potential mechanisms of acupuncture in migraine: A literature review and perspectives

Acupuncture represents one of the most widely used non-pharmacologic therapies in the treatment of migraine, offering significant benefits with few adverse effects. This literature review study sought to gather scientific evidence on the neural mechanisms and clinical applications of this ancient practice in the management of migraine, a neurologic condition that affects more than 1.25 billion people globally.

Migraine is characterized as an episodic and recurrent dysfunction of brain excitability, manifesting as moderate to severe, throbbing, unilateral headaches. It is the fifth most prevalent and seventh most disabling condition in the world. Although there are effective pharmacologic treatments such as triptans and prophylactic medications, these often present significant side effects with prolonged use. Acupuncture emerges as a promising alternative, proving to be at least as effective as conventional medications in attack prevention, as indicated in recent systematic reviews.

To better understand the effects and mechanisms of acupuncture in migraine, the researchers conducted a comprehensive systematic review of the PubMed, Science Direct, and Web of Science databases, covering publications between 1965 and 2022. The methodology included analysis of controlled clinical studies, basic research in animal models, and neuroimaging studies. Of the 1,067 articles initially identified, 56 clinical studies and 12 basic studies met the inclusion criteria, totaling 5,576 participants in the clinical trials.

The clinical results demonstrated that acupuncture provides lasting and clinically relevant benefits for patients with migraine. Thirty-three of the forty clinical studies reported positive results, including significant reduction in pain intensity (measured by scales such as VAS and SF-MPQ), decrease in attack duration and frequency, reduction in headache days, and lower need for acute attack medication. Notably, nine of ten studies that compared acupuncture with medications showed superior effects of acupuncture, especially in long-term benefits. When compared with flunarizine, topiramate, and metoprolol, acupuncture demonstrated greater efficacy in reducing the frequency, severity, and duration of pain.

In addition to benefits on pain, acupuncture showed positive effects on the comorbidities frequently associated with migraine. Approximately 40% of patients with migraine also have depression, and about 50% suffer from anxiety disorders. The reviewed studies demonstrated that acupuncture reduced anxiety and depression, increased self-esteem, and significantly improved patients' quality of life, measured through specific scales such as MSQ and SF-36.

The neurobiologic mechanisms underlying the effects of acupuncture were investigated through basic studies in animal models of migraine. This research revealed that acupuncture can protect against neuroinflammation and neuronal sensitization, two fundamental processes in the pathophysiology of migraine. Neuroinflammation is initiated by activation of the trigeminovascular system, leading to the release of neuropeptides such as CGRP, substance P, and PACAP into the perivascular space. Acupuncture has demonstrated the capacity to significantly reduce levels of these neuropeptides, both in plasma and in specific brain regions related to pain.

The research also showed that acupuncture modulates the activation of dural immune cells, including macrophages and mast cells, and reduces the release of inflammatory mediators such as interleukins, prostaglandins, and tumor necrosis factor. These anti-inflammatory effects contribute to the reduction of peripheral and central sensitization, processes that maintain chronic pain in migraine. Additionally, acupuncture influences important neuromodulatory systems, including the endocannabinoid and serotonergic systems, which play crucial roles in pain transmission and modulation.

Neuroimaging studies provided valuable insights into how acupuncture alters abnormal brain activity and connectivity in patients with migraine. Sixteen studies using advanced techniques such as functional magnetic resonance imaging revealed that acupuncture normalizes the function of the descending pain modulation system, particularly in the regions of the periaqueductal gray matter and rostral ventromedial medulla. These areas are fundamental for endogenous pain control and frequently exhibit dysfunction in patients with migraine.

Acupuncture also demonstrated effects on the brain's default mode network, including the anterior cingulate cortex, precuneus, and medial prefrontal cortex. These regions are involved in the emotional and cognitive processing of pain. The studies showed that acupuncture increases functional connectivity between these areas and regions of the pain modulation system, potentially explaining its effects on both pain intensity and the emotional aspects of migraine.

The clinical implications of these findings are substantial for patients and health professionals. Acupuncture offers a safe and effective alternative for the prophylactic treatment of migraine, with benefits extending beyond pain reduction to include improvement in quality of life and reduction of psychiatric comorbidities. For patients who do not tolerate conventional medications or experience significant side effects, acupuncture represents a valuable therapeutic option. The results suggest that acupuncture can be effectively integrated into conventional treatment protocols, potentially reducing dependence on medications and their associated adverse effects.

For health professionals, these findings provide a solid scientific basis for recommending acupuncture as a first-line treatment for migraine. The evidence of specific neurobiologic mechanisms helps demystify the effects of acupuncture and provides a scientific foundation for its practice. Neuroimaging studies, in particular, offer potential biomarkers for predicting treatment response and monitoring therapeutic progress.

However, the review identified several important limitations that should be considered. Many studies used placebo acupuncture control groups, which presents unique methodologic challenges, since any intervention that penetrates the skin cannot be considered truly inert. There was substantial heterogeneity among studies regarding acupuncture techniques, point selection, treatment parameters, and outcome measures. In the basic studies, the lack of standardization for the location of acupuncture points in animals and questions about the translation of human points to animal models limit the interpretation of results.

The neuroimaging studies, although promising, had limitations including small sample sizes, absence of adequate control groups, and a high probability of false positives. Many studies lack cross-validation of results through mu