Low-frequency electroacupuncture suppresses carrageenan-induced paw inflammation in mice via sympathetic post-ganglionic neurons, while high-frequency EA suppression is mediated by the sympathoadrenal medullary axis

Acupuncture has been used for thousands of years to treat pain and inflammation, but the scientific mechanisms by which it works are still not completely understood. A modern technique called electroacupuncture, which applies electrical stimulation to needles inserted at specific points of the body, has shown promising results in the treatment of inflammatory processes. This study investigated how different frequencies of electrical stimulation in electroacupuncture can activate distinct mechanisms in the nervous system to reduce inflammation.

The aim of the research was to compare the effects of low-frequency (1 Hz) versus high-frequency (120 Hz) electroacupuncture in an experimental model of inflammation in mice. The researchers used a substance called carrageenan, injected into the animals' paws, to create a controlled inflammatory process. After the injection, electroacupuncture was applied at Zusanli (ST-36), located in the leg region, for 30 minutes. To evaluate the anti-inflammatory effects, they measured paw swelling, myeloperoxidase activity (an enzyme indicating the presence of inflammatory cells), and pain sensitivity caused by the inflammation.

Additionally, they performed different experiments to identify which sympathetic nervous system pathways were involved in the observed effects.

The main results revealed that both electroacupuncture frequencies significantly reduced swelling, inflammatory cell infiltration, and pain hypersensitivity. However, it was discovered that the two frequencies work through completely different mechanisms. Low-frequency electroacupuncture exerted its anti-inflammatory effect through activation of sympathetic post-ganglionic neurons, which are nerve endings that release chemicals directly into tissues. This was confirmed by the fact that when these nerve endings were destroyed with a specific neurotoxic substance, the low-frequency effect was completely blocked.

In contrast, high-frequency electroacupuncture worked through activation of the sympathoadrenal axis, which involves the release of stress hormones (such as epinephrine) by the adrenal glands. When these glands were surgically removed, only the high-frequency effect was eliminated, without affecting the low-frequency effect.

For patients and healthcare professionals, these findings are extremely relevant because they demonstrate that electroacupuncture has solid scientific bases and that different treatment protocols can be optimized for specific situations. The fact that different frequencies activate distinct pathways of the nervous system suggests that acupuncturists can personalize treatments according to individual patient needs. For example, for conditions where more targeted local activation is desired, low frequency may be preferable, while situations that benefit from a broader systemic response may respond better to high frequency. In addition, both mechanisms converged on the activation of beta-adrenergic receptors on immune system cells, offering a common therapeutic point of action.

The study presents some important limitations that must be considered in interpreting the results. First, it was conducted exclusively in mice, and although these models are valuable for basic research, direct translation to humans requires caution. Physiological responses and neural mechanisms may differ between species. Second, only a specific model of acute carrageenan-induced inflammation was used, which may not adequately represent all types of inflammation encountered in clinical practice, especially chronic inflammatory processes.

Third, the observation time was relatively short (6 hours), providing no information about long-term effects or the durability of the observed benefits.

In conclusion, this study provides robust scientific evidence that electroacupuncture has well-defined mechanisms of action and that different stimulation frequencies can be strategically used to optimize therapeutic results. The finding that low and high frequency activate distinct neural pathways, but both culminate in anti-inflammatory effects, opens new possibilities for refining treatment protocols. Although more research is needed to confirm these findings in humans and in different clinical conditions, the results represent a significant advance in the scientific understanding of acupuncture and may contribute to its broader acceptance and integration into modern medicine as an evidence-based complementary therapy.