Mechanisms of acupuncture-electroacupuncture on persistent pain

Abstract

In the last decade, preclinical investigations of electroacupuncture mechanisms on persistent tissue injury (inflammatory), nerve injury (neuropathic), cancer, and visceral pain have increased. These studies show that electroacupuncture activates the nervous system differently in health than in pain conditions, alleviates both sensory and affective inflammatory pain, and inhibits inflammatory and neuropathic pain more effectively at 2 to 10 Hz than at 100 Hz. Electroacupuncture blocks pain by activating a variety of bioactive chemicals through peripheral, spinal, and supraspinal mechanisms. These include opioids, which desensitize peripheral nociceptors and reduce proinflammatory cytokines peripherally and in the spinal cord, and serotonin and norepinephrine, which decrease spinal N-methyl-D-aspartate receptor subunit GluN1 phosphorylation. Additional studies suggest that electroacupuncture, when combined with low dosages of conventional analgesics, provides effective pain management which can forestall the side effects of often-debilitating pharmaceuticals.

Conflict of interest statement

Conflicts of interest: The authors declare no competing interests.

Figures

Figure 1

Electroacupuncture inhibits inflammatory, neuropathic, cancer, and visceral pain in various animal models.

Figure 2

Rat and human maps of acupoints used in pain studies.

Figure 3

Mechanisms of electroacupuncture inhibition of inflammatory and neuropathic pain. Symbols + and − respectively represent enhancement and inhibition. 5-HT1AR = 5-hydroxytryptamine 1A receptors; ACC = anterior cingulated cortex; ATF-2 = activating transcription factor-2;CB2R = Cannabinoid 2 receptor; CORT = corticosterone; COX-2 = cyclooxygenase-2; EAA = excitatory amino acid; GABA = γ-aminobutyric acid; ICAM-1 = intracellular adhesion molecule-1; IL-6 = interleukin-6; IL-1β = interleukin-1beta; LC = locus coeruleus; N/OFQ = nociceptin/orphanin FQ; NE = norepinephrine; NMDAR = n-methyl-d-aspartate receptor; NRM = nucleus raphe magnus; PAG = periaqueductal grey; p-Akt = phosphorylated Akt; PGE2 = prostaglandin E2; pGluN1 = phosphorylated GluN1; SP = substance P; TNF-α = tumor necrosis factor-α.

Figure 4

Electroacupuncture inhibited the affective component of pain. Conditioned place avoidance scores, used to indicate affective response, were determined by subtracting time spent in the pain-paired compartment during preconditioning from time spent in that compartment during the post-conditioning test: the less post-conditioning time spent in the compartment, the greater the affective response. * P < 0.05 compared to sham control in CFA-injected rats. Reprinted with permission from Elsevier, Eur J Pain 16(2), 2012. EA = electroacupuncture, CFA = complete Fruend’s adjuvant.

Figure 5

Microphotographs showing distribution and co-localization of GluN1 and μ opioid receptors in rACC neurons. A, B: Sections were double-labeled with guinea pig polyclonal antibody against μ opioid receptors (A, red) and goat polyclonal antibody against GluN1 (B, green). C: Merged A and B photographs showing co-localization of μ opioid receptors and GluN1 in the rACC. Arrows point to double-labeled neurons (yellow). Scale bars=50 μm. rACC = rostral anterior cingulate cortex.

Figure 6

Mechanisms of electroacupuncture inhibition of visceral pain. Symbols + and − respectively represent enhancement and inhibition. CRF = corticotrophin-releasing factor; DRN = dorsal raphe nucleus; NK-1 = neurokinin 1; RVM = rostral ventromedial medulla; SP = substance P; TNF-α = tumor necrosis factor-α; VIP = vasoactive intestinal polypeptides; VIPR = VIP receptor; 5-HT = 5-hydroxytryptamine