Electroacupuncture Improves Survival in Rats with Lethal Endotoxemia via  the Autonomic Nervous System

Abstract

Background: Recent advances have indicated a complex interplay between the autonomic nervous system and the innate immune system. Targeting neural networks for the treatment of sepsis is being developed as a therapeutic strategy. Because electroacupuncture at select acupoints can modulate activities of the autonomic nervous system, we tested the hypothesis that electroacupuncture at specific acupoints could modulate systemic inflammatory responses and improve survival via its impact on the autonomic nervous system in a rat model of sepsis. Methods: Sprague-Dawley male rats received electroacupuncture for 45 min before and at 1, 2, or 4 h after a lethal dose of intraperitoneal lipopolysaccharide injection (6 mg/ kg). Outcomes included survival and systemic cytokine re-

Electrical Stimulation at the ST36 Acupoint Protects against Sepsis Lethality and Reduces Serum TNF Levels through Vagus Nerve- and Catecholamine-Dependent Mechanisms

“…The findings reported in the present study indicate that EA induces an anti-inflammatory mechanism that reduces TNF, IL-6, nitrite, and HMGB1 production in one of the more widely used rat models for studying polymicrobial sepsis [11] (Figure 1). These results are consistent with previously reported data in a model of septic shock induced by LPS [16] and in a model of sepsis induced by CLP [17]. …”

“…Previous studies have indicated that VN electric-stimulation during septic shock [16] and endotoxemia [14] specifically attenuates TNF production in spleen macrophages (main source of TNF in endotoxemia) through the cholinergic anti-inflammatory pathway [14], which is dependent on the anatomical and functional integrity of the VN, celiac-superior mesenteric plexus ganglia, and the splenic nerve [14]. The contribution of the VN was confirmed in the present study, as surgical vagotomy abolished the anti-inflammatory potential of electroacupuncture (Figure 4).…”

Molecular and Functional Neuroscience in Immunity

“…Stimulation of somatosensory signaling to the CNS by acupuncture activates a brain muscarinic acetylcholine receptor (mAChR) mechanism that is linked with efferent vagus nerve activity and catecholaminergic regulation that suppresses serum TNF, IL-1β, and IL-6 levels in murine endotoxemia (124). Activation of the sciatic nerve by electroacupuncture via unknown mechanisms triggers stimulation of efferent vagus nerve signaling to the adrenal medulla that results in increased dopamine release (125).…”

Neural circuitry and immunity

“…Increased acetylcholine levels in spleen of mice treated with McN-A-343 mediate anti-inflammatory drug efficacy in colitis and these effects require signaling along the vagus nerve and splenic nerve, because they are abolished in mice with vagotomy and splenic nerve transection [32]. An anti-inflammatory role of brain mAChRs has been demonstrated in experimental models of hemorrhagic shock [84,85] and in mediating the anti-inflammatory efficacy of acupuncture [86]. In addition, peripheral administration of the centrally-acting M1 mAChR agonist xanomeline significantly suppresses serum TNF and improves survival in murine endotoxemia [87].…”