Electroacupuncture affects immunity through a specific dopaminergic neuroendocrine pathway

Electroacupuncture – immunity – dopaminergic pathway

A new study, published in the February 23, 2014 issue of Nature Medicine provides perhaps the first robust evidence that electroacupuncture effects are translated through specific neuroendocrine and immune pathways.

The way acupuncture affects human physiologic processes, and particularly immune function and homeostasis, is not well understood.

Acupuncture has always been considered part of  ‘Eastern’ medicine and a type of  ‘alternative’ medicine not typically utilized by clinicians in critical scenarios.

In the Nature Medicine study, Torres-Rosas et al. administer electroacupuncture to mice challenged with LPS or mice with polymicrobial peritonitis, in combination with neurectomies and vagotomies.

In LPS-challenged mice, electroacupuncture was found to inhibit pro-inflammatory cytokine production in a voltage-dependent manner, in non-adrenalectomized animals only, in addition to decreasing mortality, morbidity, and weight loss. Interestingly, sciatic neurectomy and vagotomy both abolished this anti-inflammatory effect.

Electroacupuncture use was associated with increased catecholamine levels, but only dopamine appeared to be required to inhibit TNF-production. This effect was most likely mediated by D1 receptors as the selective D1/dopamine receptor agonist fenoldopam prevented mortality in animals with polymicrobial peritonitis as did electroacupuncture.

These findings not only elucidate a heretofore unrecognized complex pathway for the potential efficacy of electroacupuncture in critically ill patients but also suggest additional therapeutic modalities that merit further research.

Source: Nature Medicine (2014) doi:10.1038/nm.347
Read More: Nature Medicine

Updates

The authors of  a 2020 study developed an intersectional genetic strategy to manipulate sympathetic cells expressing neuropeptide Y (NPY) in sympathetic ganglia and/or adrenal glands. Using lipopolysaccharide (LPS)-induced endotoxemia as a model they demonstrate that electroacupuncture stimulation can activate distinct sympathetic pathways and modulate systemic inflammation in somatotopy-, stimulation intensity-, and disease state-dependent manners.

Specifically, the authors report that electroacupuncture stimulation with low intensity at hindlimb regions drives the vagal-adrenal axis, producing anti-inflammatory effects that depend on NPY+ adrenal chromaffin cells. High intensity ES at the abdomen activates NPY+ splenic noradrenergic neurons via the spinal-sympathetic axis; these neurons engage incoherent feedforward regulatory loops via activation of distinct adrenergic receptors (ARs), and their ES-evoked activation produces either anti- or pro-inflammatory effects due to disease state-dependent changes in AR profiles.

A 2021 study provides a neuroanatomical explanation for the presence of acupoint selectivity and acupoint specificity in driving a specific autonomic pathway: the vagal–adrenal axis.

Thus, the authors of this study give two examples: First, for low-intensity electroacupuncture stimulation, deep but not superficial stimulation of the ST36 site is crucial for driving the vagal–adrenal axis, which probably reflects the requirement of electric needle tips close to the major nerve bundles containing PROKR2^ADV fibres that innervate deep limb fascia. And second, the spinal sympathetic reflexes, which are independent of PROKR2^ADV neurons, can be evoked by high-intensity ES at both ST25 and ST36 acupoints.

In a 2021 commentary about the above-mentioned article, Luis Ulloa, an expert in this field, explains that The leg Zusanli (ST36) acupoint, located about 2 centimetres below the knee in humans, is the most frequently stimulated site for relieving inflammation. Importantly, he notes that electroacupuncture stimulation of ST36 can induce opposing effects depending on the intensity. Whereas high-intensity ES of ST36 activates the sympathetic nervous system, which supports ‘fight or flight’ responses to stress, low-intensity stimulation activates the parasympathetic nervous system, which regulates physiological functions that occur during rest.

The authors of a 2022 study determined whether activation of the sciatic–vagal network by electroacupuncture on ST36 acupoint can alleviate arthritis and inflammation in susceptible C3H/HeJ mice infected with a bioluminescent strain of B. burgdorferi N40.

The most pronounced effects of electroacupuncture stimulation treatment in infected mice were a significant reduction in Th17 cell-derived IL-17A, IL-17F, and IL-22 cytokines in the heart at 4 weeks p.i. Electroacupuncture stimulation treatment also reduced splenic IL-22 levels significantly. Of note, EA was even more effective in reducing TNF-α and IL-2 levels in the heart and TNF-α levels in the spleen.

The authors suggest a model where the neuromodulation of the brain through sciatic nerve electrostimulation by electroacupuncture  results in signaling of adrenal glands through vagus nerve to produce dopamine. Binding of dopamine neurotransmitter to receptor present on lymphocytes results in activation of Tregs, which then suppress Th1- and Th17-mediated inflammatory Lyme arthritis.