Probing the Effects and Mechanisms of Electroacupuncture at Ipsilateral or Contralateral ST36–ST37 Acupoints on CFA-induced Inflammatory Pain

Huang

et al. 2017

Sci Rep

Self Cite

Although inflammatory pain is a common clinical condition, its mechanisms are still unclear. Electroacupuncture (EA), a well-known method of pain management, may reduce inflammatory pain by regulating neurons, astrocytes, and inflammatory signaling pathways. Injections of complete Freund’s adjuvant (CFA), which can initiate cell-mediated inflammatory pain, resulted in significant hyperalgesia, which was subsequently prevented by EA. In CFA-injected mice, a dramatic increase was observed in the expression of the following proteins in the dorsal root ganglion and spinal cord dorsal horn: the astrocytic marker GFAP, S100B, RAGE, pPKCε, COX-2, pERK, and pNFκB. These effects were reversed by EA. In addition, mechanical hyperalgesia was significantly reduced in the N6-cyclopentyladenosine (CPA) i.p. or i.m. and endomorphin (EM) i.p. groups. Neither EM i.m. nor EM i.p. exhibited any analgesic effect on thermal hyperalgesia. However, both CPA i.m. and CPA i.p. attenuated thermal hyperalgesia in the mouse inflammatory pain model. We showed that CPA reduced COX-2 and pPKCε expression. However, EM administration did not reduce COX-2 levels. Combined administration of naloxone and rolofylline increased pPKCε and COX-2 pathways. Taken together, our study results revealed a novel and detailed mechanism of EA-induced analgesia that involves the regulation of the opioid and adenosine pathways.

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Electroacupuncture Attenuates Induction of Inflammatory Pain by Regulating Opioid and Adenosine Pathways in Mice

Liao

Huang

et al. 2017

Sci Rep

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“…Mice were anesthetized with 1% isoflurane and given a single injection of 20 μ l saline (pH 7.4, buffered with 20 mM HEPES) or CFA (75% in saline, 0.5 mg/ml heat-killed M. tuberculosis [Sigma, St. Louis, MO]) in the plantar surface of the hind paw to induce chronic intraplantar inflammation [ 19 ]. Behaviour tests are conducted every 3 days after induction of chronic inflammatory pain.…”

Section: Methodsmentioning

confidence: 99%

Role of Transient Receptor Potential Vanilloid 1 in Electroacupuncture Analgesia on Chronic Inflammatory Pain in Mice

Yang

BioMed Research International

Lin

2017

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Chronic inflammatory pain may result from peripheral tissue injury or inflammation, increasing the release of protons, histamines, adenosine triphosphate, and several proinflammatory cytokines and chemokines. Transient receptor potential vanilloid 1 (TRPV1) is known to be involved in acute to subacute neuropathic and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are not elucidated. Our results showed that EA significantly reduced chronic mechanical and thermal hyperalgesia in the chronic inflammatory pain model. Chronic mechanical and thermal hyperalgesia were also abolished in TRPV1−/− mice. TRPV1 increased in the dorsal root ganglion (DRG) and spinal cord (SC) at 3 weeks after CFA injection. The expression levels of downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of pERK, pp38, and pJNK. Transcription factors (pCREB and pNFκB) and nociceptive ion channels (Nav1.7 and Nav1.8) were involved in this process. Inflammatory mediators such as GFAP, S100B, and RAGE were also involved. The expression levels of these molecules were reduced in EA and TRPV1−/− mice but not in the sham EA group. Our data provided evidence to support the clinical use of EA for treating chronic inflammatory pain.

“…The NR1, NR2A, NR2B, and NR2D subunits are distributed in the DRG and SC [19,20]. Activation of NRs can induce the influx of Ca 2+ and then lead to the activation of Ca 2+ /calmodulin-dependent protein kinase 2 (CaMKII) for signaling in the postsynaptic density [21]. There are four isomers of CaMKII in mammals, i.e., α, β, γ, and δ. CaMKII is a holoenzyme and a serine/threonine kinase that is highly expressed in the brain mainly participates in its phosphorylation [22].…”

Section: Introductionmentioning

confidence: 99%

TRPV1 is a Responding Channel for Acupuncture Manipulation in Mice Peripheral and Central Nerve System

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Acupuncture involves inserting a fine needle into a specific point, often called an acupoint, thereby initiating a therapeutic effect accompanied by phenomena such as soreness, heaviness, fullness, and numbness. Acupoints are characterized as points located in deep tissues with abundant sensory nerve terminals, which suggests that there is a strong relationship between acupoints and peripheral sensory afferents. In this study, we determined whether manual acupuncture (MA) or different frequencies of electroacupuncture (EA) share similar mechanisms for activating excitatory neurotransmission. Methods: We performed MA or EA at acupoint ST36 and we also used western blot and immunostaining techniques to determine neural changes at the peripheral dorsal root ganglion (DRG), spinal cord (SC), and somatosensory cortex (SSC) levels. Results: Our results show that either MA or EA at the ST36 acupoint significantly increased components of the TRPV1-related signaling pathway, such as pPKA, pPI3K, pPKC-pERK, and pAKT (but not pp38 or pJNK) at the peripheral DRG and central SC-SSC levels. Furthermore, excitatory phosphorylated N-methyl-D-aspartate receptor (pNMDA) and pCaMKIIα (but not pNR2B, pCaMKIIδ, or pCaMKIIγ) also increased. These molecules could not increase in the DRG and SC-SSC of TRPV1^–/–mice. Conclusion: Our data demonstrates that both MA and EA can activate excitatory signals in either peripheral or central levels. We also define that TRPV1 is crucial for an acupuncture effect and then initiate excitatory pNR1-pCaMKII pathway, at peripheral DRG and central SC-SSC level. We suggest that the TRPV1 signaling pathway is highly correlated to Acupuncture effect that implies the real clinical significance.