Electroacupuncture therapy in inflammation regulation: current perspectives

Figures & data

Figure 1 Sympathetic connection to immune cells in target organs.

Notes: Splanchnic nerve activity transmitted to the celiac ganglion may increase the release of norepinephrine (NE) of adrenergic postganglionic neurons. This in turn would activate immune-cell responses in target organs, such as macrophages in the spleen and T_H2 cells in the liver, and these cells regulate the production of pro- and anti-inflammatory cytokines. Vagal input, which has not been clearly identified, may have similar effects on the regulation of inflammation as sympathetic activity.

Abbreviations: T_H, T helper; ACh, acetylcholine; iNKT, invariant natural killer T.

Table 1 Summary of electroacupuncture (EA) studies on the regulation of inflammation in experimental animals

Animal model	Acupoints	Major EA effects	Reference(s)
Intestinal ischemia–reperfusion injury	ST36, ST36 plus stem-cell transplantation	Increased crypt-cell-proliferation index and mucosal mRNA expression of SDF1, CXCR4, EGF, and EGFR Decreased mucosal NFκB, p65 and serum inflammation factor (TNFα, IL6)	^Citation97
Spinal cord ischemia–reperfusion injury	GV6, GV9, EX-B2	Decreased TNFα, IL1β, and MMP9 Neuroprotective effects of EA suppressed by autophagic inhibitor (3-methyladenine)	^Citation98
TNBS-induced colitis	ST36, ST36 plus VNS	Decreased TNFα, IL1β, IL6, and MPO Increased vagal activity and decreased sympathetic activity	^Citation13
	PC3 and PC6	Decreased IL1β and NFκB	^Citation99
CPB-induced lung injury	PC6 and LI4	Decreased pp38, pJNK, and caspase 3 Increased SOD activity	^Citation6
Thermal injury-induced remote acute lung injury	ST36	Decreased IL1β, IL6, and HMGB1	^Citation100
CFA-induced inflammation	ST36–ST37	Decreased TRPV1, pERK, pp38, pJNK, pAkt, pCREB, Nav1.7, and Nav1.8 in DRG and Schwann cells	^Citation44, ^Citation45
	ST36	Decreased GFAP, IBA1, S100β, RAGE, and TRPV1, in the DRG and spinal cord dorsal horn Blocking opioid and adenosine A1 receptors reversed the effects of EA	^Citation45
	ST36 and GB34	Increased apelin, APJ protein, and mRNA expression in the spinal cord	^Citation101
	ST36 and BL60	Decreased mRNA and protein levels of TLR4, MYD88, and NFκB in ankle-bone tissue	^Citation102
	GB30	Increased plasma ACTH levels Increased phosphorylation of NR1 in CRH-containing neurons in the PVN	^Citation46
Electrical stimulation-induced migraine	GB20 and TE5	Decreased serum CGRP and PGE2 Decreased IL1β and COX2 expression in the trigeminal ganglion Decreased plasma protein extravasation CB1-receptor antagonism reversed the effects of EA	^Citation103
Septic brain injury	GV20, ST36	Decreased TNFα, IL6, and MDA Increased SOD and catalase activities in the serum and hippocampus Decreased TLR4, NFκB and IBA1 expression	^Citation104
MPTP-induced Parkinson’s disease	ST36 and SP6	Increased human placental alkaline phosphatase Decreased microglia activation in the striatum and midbrain	^Citation87
Obesity	CV12 and CV4	Decreased serum TNFα	^Citation105
	ST36	Decreased adipose tissue inflammation Decreased HIFα, hypoxia-related genes (VEGFA, SLC2AL, and GPX1), and inflammation-related genes (TNFA, IL6, and MCP1) Decreased macrophage recruitment and infiltration Decreased NFκB and increased IκBα	^Citation106
Collagen-induced rheumatoid arthritis	ST36, GB39, BL23	Decreased levels of NFκB (p65), TNFα, IL1β, IL6, and IL8	^Citation48
	GB39, ST36	Increased mRNA expression of VPAC1 Elevated CD4^+FOXP3^+ Treg-cell frequency and reduced CD4^+IL17^+ TH17-cell frequency	^Citation107
	ST36	Analgesic effect of EA was mediated by mAChR, 5HT1A, and 5HT3 receptors, but not by 5HT2 receptor	^Citation47
Ligature-induced periodontitis	LI4, LI11, ST36, ST44	Decreased TRAP-positive multinucleated cells Decreased expression of IL1β and MMP8 mRNAs Increased expression of IL6 mRNA	^Citation108
Cerebral ischemia–reperfusion injury	GV20 and ST36	Decreased ACTH and HSP70	^Citation2
	GV20 and GV14	Increased rCBF and IL6 expression Decreased IL1β and JAK2	^Citation109
	GV20 and GV14	Decreased mRNA level of ChAT, five subtypes of muscarinic receptors and α7 nAChR	^Citation92
	GV20 and GV14	Decreased Bax, TNFα, IL6, and IL1β Decreased excitotoxicity by NMDA Increased antioxidant systems (Bcl2, Nrf2, GCSh, GCSl, Gsh)	^Citation110
	LI11 and ST36	Decreased microglia activation of IBA1 and ED1 in cortex Decreased serum TNFα, IL1β, and IL6 Decreased cortical p38 MAPK and MyD88 Decreased cortical NFκB, TNFα, and IL1β	^Citation78, ^Citation111
	GV20 and ST36	Inhibited neuronal apoptosis, microglial activation of IBA1, and oxidative stress in the hippocampus Decreased hippocampal and serum IL6 and TNFα levels	^Citation79
	LI11 and ST36	Decreased TLR4/NFκB signaling and levels of TNFα, IL1β, and IL6	^Citation112

Abbreviations: HT, hydroxytryptamine; ACTH, adrenocorticotrophic hormone; APJ, apelin receptor; CFA, complete Freund’s adjuvant; CGRP, calcitonin gene-related peptide; CPB, cardiopulmonary bypass; CRH, corticotrophin-releasing hormone; DRG, dorsal root ganglion; Gsh, glutathione; MDA, malondialdehyde; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NMDA, N-Methyl-d-aspartic acid; PGE2, prostaglandin E₂; PVN, paraventricular nucleus; rCBF, regional cerebral blood flow; TG, trigeminal ganglion; TNBS, 2,4,6-trinitrobenzenesulfonic acid.

Figure 2 Possible neural pathways that transmit cutaneous ASs ultimately to internal visceral organs and induce anti-inflammatory responses in target organs.

Abbreviations: AS, acupuncture signal; NTS, nucleus tractus solitarius; DMV, dorsal motor nucleus of vagus nerve; NA, nucleus ambiguus.

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