Modulatory effects of acupuncture on raphe nucleus-related brain circuits in patients with chronic neck pain: A randomized neuroimaging trial

Neck pain is a very common condition in the population, affecting more than 30% of people annually and ranking as the fourth leading cause of disability worldwide. Although many acute episodes resolve spontaneously, about half of patients continue to experience some degree of pain or recurrent episodes, becoming a chronic problem that significantly impacts quality of life. Treatment has traditionally been based on medications such as analgesics and anti-inflammatories; however, these can cause important side effects, including fatigue, nausea, headaches, and even chemical dependence with prolonged use. Furthermore, the cost of pharmacologic management of back and neck pain exceeds 100 billion dollars in the United States alone, creating an urgent need for safer and more effective alternative treatments.

Acupuncture has been widely used for the treatment of neck pain, but its efficacy remains controversial in the scientific literature. Previous clinical studies have shown mixed results, possibly due to heterogeneous methodologies and a lack of understanding of the brain mechanisms through which acupuncture acts. One area of particular interest is the brain's serotonergic system, specifically the raphe nuclei, which are important sources of serotonin and play a crucial role in endogenous pain control, including pain inhibition, negative affect, and passive coping. This neuronal circuit shows high congruence with the regions where serotonin acts and represents a fundamental component of the descending pain regulation network.

This randomized controlled trial aimed to investigate the efficacy of true acupuncture compared with sham acupuncture in the treatment of patients with chronic neck pain, using both clinical assessments and functional neuroimaging to understand the brain mechanisms involved. Researchers recruited 99 patients with chronic neck pain from university hospitals in China, aged 18 to 65 years, who had pain for at least three months and a score of 4 or higher on a 0-to-10 pain scale. Participants were randomized in a 2:1 ratio to receive true acupuncture or sham acupuncture over four weeks, with three sessions per week, totaling 12 treatment sessions of 30 minutes each.

In the true acupuncture group, five specific points were selected based on each patient's individual tenderness, including traditional Chinese medicine points such as Tianliao, Jianwaishu, Jianzhongshu, Dazhu, and Jugu. Needles were inserted at depths of 0.5 to 1.5 cm with manipulation to obtain the "deqi" sensation, which includes numbness, tingling, or fullness, indicating effective stimulation. In the sham acupuncture control group, five points that did not correspond to traditional acupuncture points were used, with superficial insertion of only 2 mm without manipulation to avoid the deqi sensation. All participants also underwent functional MRI before and after treatment to assess changes in raphe nuclei-related brain circuits.

The clinical results clearly demonstrated the superiority of true acupuncture over sham acupuncture. The primary outcomes, which included pain intensity measured by the visual analog scale and the duration of each pain episode, showed significant improvements in the true acupuncture group. Pain intensity decreased by an average of 16.9 mm on the scale, while in the sham group the reduction was only 5.41 mm without statistical significance. The duration of each pain episode decreased by 4.3 hours in the true acupuncture group compared with 2.06 hours in the sham group.

Secondary outcomes also favored true acupuncture, including significant improvements in the Neck Disability Index, the Northwick Park Neck Pain Questionnaire, the McGill Pain Questionnaire, the anxiety and depression scales, and patients' overall quality of life.

The neuroimaging analyses revealed fascinating findings about how acupuncture modulates pain-related brain circuits. The researchers focused specifically on two subdivisions of the raphe nuclei: the dorsal raphe nucleus and the median raphe nucleus. True acupuncture increased functional connectivity between the dorsal raphe nucleus and the thalamus, a region crucial for pain processing, while decreasing connectivity with the lingual gyrus and the middle frontal gyrus. For the median raphe nucleus, acupuncture increased connectivity with regions of the limbic system, including the amygdala, the bilateral insula, and the parahippocampal gyrus—areas important in emotional pain processing—while reducing connectivity with the medial frontal cortex.

These changes suggest that acupuncture acts by reconfiguring the neural circuits responsible for both sensory and emotional processing of pain.

The clinical implications of this study are significant for patients and health care professionals. The results provide robust scientific evidence that acupuncture is more effective than a placebo procedure for treating chronic neck pain, going beyond a simple psychological effect. For patients, this means a valid non-pharmacologic treatment option that can reduce reliance on analgesic medications and their associated side effects. Acupuncture showed benefits not only in pain intensity but also in the duration of pain episodes, neck function, emotional well-being, and overall quality of life.

For health care professionals, the findings offer a solid scientific basis for recommending acupuncture as part of a comprehensive treatment plan for chronic neck pain.

The study also revealed interesting correlations between changes in brain circuits and clinical improvements. The modifications in dorsal raphe nucleus connectivity correlated specifically with improvements in pain intensity and duration, while changes in the median raphe nucleus were associated with improvements in quality of life and emotional aspects related to pain. This suggests that different subdivisions of the raphe nuclei may have specific roles in pain treatment through acupuncture, with the dorsal nucleus more related to the sensory aspects of pain and the median nucleus to emotional aspects.

It is important to acknowledge some limitations of this study. First, it was conducted at a single center in China, which may limit the generalizability of the results to other populations and cultural contexts. Second, due to the nature of the intervention, acupuncturists could not be blinded to the treatment, although other researchers responsible for assessments remained blinded. Third, the treatment was individualized based on the sens