Dopamine mediates vagal modulation of the immune system by electroacupuncture

Abstract

Previous anti-inflammatory strategies against sepsis, a leading cause of death in hospitals, had limited efficacy in clinical trials, in part because they targeted single cytokines and the experimental models failed to mimic clinical settings1-3. Neuronal networks represent physiological mechanisms selected by evolution to control inflammation that can be exploited for the treatment of inflammatory and infectious disorders3. Here, we report that sciatic nerve activation with electroacupuncture controls systemic inflammation and rescues mice from polymicrobial peritonitis. Electroacupuncture at the sciatic nerve controls systemic inflammation by inducing a vagal activation of DOPA decarboxylase leading to the production of dopamine in the adrenal medulla. Experimental models with adrenolectomized animals mimic clinical adrenal insufficiency4, increase the susceptibility to sepsis, and prevent the anti-inflammatory potential of electroacupuncture. Dopamine inhibits cytokine production via dopaminergic type-1 receptors. Dopaminergic D1-agonists suppress systemic inflammation and rescue mice from polymicrobial peritonitis in animals with adrenal insufficiency. Our results suggest a novel anti-inflammatory mechanism mediated by the sciatic and the vagus nerves modulating the production of catecholamines in the adrenal glands. From a pharmacological perspective, selective dopaminergic agonists mimic the anti-inflammatory potential of electroacupuncture and can provide therapeutic advantages to control inflammation in infectious and inflammatory disorders.

Defining the Quality of Acupuncture

“…31 Electro-acupuncture at Zusanli controls systemic inflammation by the production of dopamine in the adrenal medulla, and dopamine inhibits cytokine production. 32 Animal or clinical evidence for regulating immunity and/or reducing inflammation was available for most of the acupuncture points used in the clinical trials for CRF. The causes and manifestations of CRF are multifactorial.…”

Dopamine Receptor D3 Signaling on CD4+ T Cells Favors Th1- and Th17-Mediated Immunity

“…Given that CD4 + T cells not only play a key role in protecting the organism from various threats but are also potentially harmful to self-tissues, their function needs to be under stringent control. Dopamine (DA) is typically recognized for controlling complex processes such as locomotion, cognition, hormone secretion, renal function, and intestinal motility; however, recent evidence points to DA as a key regulator of the immune response involved in sepsis, autoimmune diseases, and neurodegenerative disorders (4)(5)(6)(7)(8). DA operates through engagement of five different DA receptors, termed DRD1-DRD5.…”

The endocannabinoid system in pain and inflammation: Its relevance to rheumatic disease

“…Other neural-immune reflexes such as dopamine and electro-acupuncture based circuits also exist but are less-well defined, as shown in Figure 4 (75). The effects of acupuncture stimulation on neural reflex immunity circuits provides important and exciting insights into the regulation of innate immunity and the discovery of new targets as anti-inflammatory therapeutics (76).…”