Mediators, Receptors, and Signalling Pathways in the Anti-Inflammatory and Antihyperalgesic Effects of Acupuncture

Table 1

Effects of electroacupuncture and manual acupuncture on inflammatory signalling pathways and receptors.

Author and year	Model	EA/acup	Acupuncture points	Effect	Thermal hyperalgesia	Mechanical allodynia	Oedema
Huang et al.; 2004 [10]	CFA hind paw FSD rats	EA 100 Hz	(B) ST 36, SP 6		No effect	Reduced
Huang et al.; 2008 [11]	CFA hind paw FSD rats	EA 100 Hz	(B) ST 36, SP 6	Reduced thermal hyperalgesia and increased EA tolerance; EA effects abolished by high dose Naloxone suggesting dynorphin mediation	Reduced
Su et al.; 2011 [12]	CFA hind paw MSD rats	EA 2 Hz	(I) GB 30, GB 34	Increased POMC and β-END expression in keratinocytes, macrophages, and T-lymphocytes in inflamed skin via activation of CB2 cannabinoid receptors	Reduced	Reduced
Zhang et al.; 2012 [13]	CFA hind paw rats	EA 10 Hz	GB 30	Suppressed spinal IL-17 and p-NR1	Reduced	Reduced
Shou et al.; 2013 [14]	CFA hind paw MSD rats	EA 2 Hz; EA 100 Hz	ST 36, BL 60	Increased CB1 expression with upregulation of D1 and D2 expression in striatum	Reduced
Fang et al.; 2013 [5]	CFA hind paw MSD rats	EA 2/100 Hz alt	(B) ST 36, BL 60	Inhibition of p38/MAPK/ATF-2/TRPV1 pathway producing downregulation of TRPV1 in spinal dorsal horn		Reduced	Reduced; only at day 14
Fang et al.; 2014 [15]	CFA hind paw MSD rats	EA 2/100 Hz alt	(B) ST 36, BL 60	Inhibited ERK1/2-COX-2 and ERK1/2-CREB-NK-1 pathway Downregulated NK-1 hence inhibiting SP		Reduced
Wang et al.; 2013 [9]	CFA hind paw M Wistar rats	EA 100 Hz	(B) GB 30	EA effects suppressed by opiate antagonists naloxone and natrindole	Reduced	Reduced	Reduced; slightly
Wang et al.; 2014 [16]	CFA hind paw M Wistar rats	EA 100 Hz	(B) GB 30	TNF-α and IL-1β downregulated,; IL-13 upregulated, and IL-1α and IL-4 unchanged; IFN-γ up-regulated stimulating CXCL10 increasing CXCR3+ macrophages	Reduced	Reduced
Du et al.; 2014 [4]	CFA hind paw MSD rats	EA 2/100 Hz alt	(B) ST 36, BL 60	Inhibited JNK1/2 and COX-2 but not TRPV1		Reduced	No effect
Chen et al.; 2011 [17]	Carrageenan & CFA hind paw CDI mice	EA 2 Hz	ST 36	Decreased overexpression of ASIC3 in DRG		Reduced
Huang et al.; 2013 [18]	Carrageenan & CFA hind paw F ICR mice	EA 2 Hz	ST 36	Decreased expression of sodium voltage-gated channels Nav 1.7 and Nav 1.8 but not Nav 1.9 in DRG	Reduced	Reduced
Kim et al.; 2012 [19]	Carrageenan hind paw MSD rats	EA 2/100 Hz alt	(B) ST 36, SP 6	Inhibition of p-PI3K blocked trkA/PI3K/PIP3/Akt pathway	Reduced	Reduced
da Silva et al. 2015 [20]	Carrageenan gastrocnemius C57BL/6 mice	Manual acup	SP 6	Increased IL-10 in inflamed muscle; Induced a phenotypic switch from M1 to M2 macrophages in inflamed muscle	Reduced	Reduced	Reduced
Kim et al.; 2009 [21]	Capsaicin hind paw; MSD rats	EA 2 Hz	(I) SI 3, TE 8; (GB 30, GB 34; BL 40, BL 60; GV 2, GV 6; LI 3, LI 6)	SI 3 & TE 8 effective, but other point combinations were not; Secondary (but nor primary) hyperalgesia is mediated by MOR and DOR but not KOR or adrenergic receptors		Reduced; secondary but not primary hyperalgesia
Hwang et al.; 2011 [22]	Exp. diabetic neuropathic pain MSD rats	EA 2 Hz; EA 120 Hz	(B) SP 9 or ST 36	Decreased cleavage of p35 to p25 hence inhibited p35/p25/Cdk5/MAPK and/or p35/p25/Cdk5/NMDA pathways	EA 2 Hz reduced; EA 120 Hz; no effect	EA 2 Hz reduced; EA 120 Hz no effect
Jiang et al.; 2013 [23]	SNL MSD rats	EA 2 Hz	(I) ST 36, BL 60	Downregulated TRPV1 in spinal dorsal horn and reduced CGRP		Reduced
Lee et al.; 2013 [24]	SCI MSD rats	Manual acup	GV 26, (B) GB 34	Inhibited JNK/p-c-Jun in spinal astrocytes; Decreased chemokines MCP-1, MIP-1β, and MIP-3α	Reduced	Reduced
Yu et al.; 2013 [25]	CCI SD rats	EA 2 Hz; EA 15 Hz	ST 36, GB 34	EA reduced ERK1/2 phosphorlylation and P2X3 expression in spinal cord	Reduced; EA 2 Hz > 15 Hz	Reduced; EA 2 Hz > 15 Hz
Hsu et al.; 2014 [26]	CCI MSD rats	EA 2 Hz; EA 15 Hz	(R) ST 36, ST 37	EA increased cerebral TRPV4 but not TRPV1 No change in spinal TRPV4 or TRPV1	Reduced	Reduced
Wang et al.; 2009 [27]	Surgical trauma MSD rats	EA 2/60 Hz alt	(B) ST 36, Lanwei (M-LE-13)	Suppressed lymphocyte proliferation; Reduced splenic T cells production of Th1 cytokines (IL-2 and IFN-γ) increased Th2 cytokines (IL-4, IL-10); Suppressed activity of ERK1/2, p38, NF-κB, and AP-1	Reduced	Reduced

EA: electroacupuncture, acup: acupuncture, CFA hind paw: model of inflammation induced by injection of complete Freund’s adjuvant into rats’ hind paws, FSD rats: female Sprague Dawley rats, MSD: male Sprague Dawley rats, alt: alternating, (B): bilateral, (I): ipsilateral, CB: cannabinoid receptor, D: dopamine receptor, TRPV: transient receptor potential vallinoid, proopiomelanocortin, β-END: beta endorphin, p-NR1: phosphorylation of NR1, SP: substance P, CGRP: calcitonin gene-related peptide, NK-1: neurokinin 1 receptor, DRG: dorsal root ganglion, MAPK: mitogen activated protein kinase, ATF-2: activating transcription factor 2, ERK: extracellular-regulated protein kinase, CREB: cAMP response element binding protein, NK-1: neurokinin 1 receptor, JNK: c-jun N terminal kinase, ASIC3: acid sensing ion channel 3, Nav: sodium voltage-gated channels, trkA: tyrosine kinase A, PI3K/PIP3: phosphatidylinositol 3 kinase/phosphatidylinositol phosphate 3 pathway, MOR: Mu opioid receptor, DOR: delta opioid receptor, KOR: kappa opioid receptor, AP-1: activator protein 1, Cdk5: cyclin-dependent kinase 5, and NMDA: N-methyl-D-aspartate.