Long‐term antinociception by electroacupuncture is mediated via peripheral opioid receptors in free‐moving rats with inflammatory hyperalgesia

Wang, Y.; Hackel, Dagmar; Peng, Fei; Rittner, Heike L.

doi:10.1002/j.1532-2149.2013.00325.x

Cited by 24 publications

(25 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A reproducible electroacupuncture protocol in free moving rats performed right after injection of CFA and at 24 h post CFA using 3D image computer modeling was previously established [10]. Rats were randomly divided into CFA+EA (EA) and CFA control (CFA) group and were carefully habituated within the sterilized disposable paper cap three days before experiment.…”

Section: Methodsmentioning

confidence: 99%

“…Endogenous opioid peptides such as beta-endorphin (END) also could contribute to acupuncture-induced analgesia. They activate opioid receptors both at the level of the spinal cord [7], [8] as well as on peripheral sensory neurons at the site of inflammation [9], [10]. Acupuncture triggers END transcription and translational in the inflamed tissue and this was attenuated by a CB2 antagonists [11].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

CXCL10 Controls Inflammatory Pain via Opioid Peptide-Containing Macrophages in Electroacupuncture

et al. 2014

View full text Add to dashboard Cite

Acupuncture is widely used for pain treatment in patients with osteoarthritis or low back pain, but molecular mechanisms remain largely enigmatic. In the early phase of inflammation neutrophilic chemokines direct opioid-containing neutrophils in the inflamed tissue and stimulate opioid peptide release and antinociception. In this study the molecular pathway and neuroimmune connections in complete Freund's adjuvant (CFA)-induced hind paw inflammation and electroacupuncture for peripheral pain control were analyzed. Free moving Wistar rats with hind paw inflammation were treated twice with electroacupuncture at GB30 (Huan Tiao - gall bladder meridian) (day 0 and 1) and analyzed for mechanical and thermal nociceptive thresholds. The cytokine profiles as well as the expression of opioid peptides were quantified in the inflamed paw. Electroacupuncture elicited long-term antinociception blocked by local injection of anti-opioid peptide antibodies (beta-endorphin, met-enkephalin, dynorphin A). The treatment altered the cytokine profile towards an anti-inflammatory pattern but augmented interferon (IFN)-gamma and the chemokine CXCL10 (IP-10: interferon gamma-inducible protein) protein and mRNA expression with concomitant increased numbers of opioid peptide-containing CXCR3+ macrophages. In rats with CFA hind paw inflammation without acupuncture repeated injection of CXCL10 triggered opioid-mediated antinociception and increase opioid-containing macrophages. Conversely, neutralization of CXCL10 time-dependently decreased electroacupuncture-induced antinociception and the number of infiltrating opioid peptide-expressing CXCR3+ macrophages. In summary, we describe a novel function of the chemokine CXCL10 - as a regulator for an increase of opioid-containing macrophages and antinociceptive mediator in inflammatory pain and as a key chemokine regulated by electroacupuncture.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CXCL10 Controls Inflammatory Pain via Opioid Peptide-Containing Macrophages in Electroacupuncture

et al. 2014

View full text Add to dashboard Cite

show abstract

“…EA has been widely accepted as an alternative method for the treatment of pain, such as migraine [31], neuropathic pain [32], visceral pain [33], and inflammatory pain [34]. However, AEA is another auxiliary acupuncture method that inserts needle into the auricle.…”

Section: Discussionmentioning

confidence: 99%

Effects and mechanisms of auricular electroacupuncture on gastric hypersensitivity in a rodent model of functional dyspepsia

Zhou

Wang

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

BackgroundFunctional dyspepsia (FD) is a common functional gastrointestinal disease, and abdominal pain is one of the main symptoms. The aim of this study was to explore the effects and mechanisms of auricular electro-acupuncture (AEA) on gastric hypersensitivity in a rodent model of FD.MethodsTen-day-old pups were gavaged with 0.2 ml of 0.1% iodoacetamide daily for 6 days. AEA at the “stomach” point with different parameters or sham-EA was performed on 8-week-old animals. Gastric sensitivity to gastric distention was measured under different conditions. Autonomic functions were assessed from the spectral analysis of heart rate variability (HRV) derived from the electrocardiogram. Naloxone was injected intraperitoneally before AEA to explore the opioid mechanism. Gastric emptying was measured at the end of the study.Results1) Gastric sensitivity to gastric distention was higher in the FD rats. AEA with parameters of 0.1s on, 0.4s off, 100Hz, 0.3ms and 0.4–0.5mA, but not other parameters or sham-EA, decreased gastric hypersensitivity in the FD rats. Naloxone did not block the effect of AEA. 2) Lower vagal activity and higher sympathovagal ratio were noted in the FD rats, compared with the controls. AEA increased vagal activity and improved sympathovagal imbalance.ConclusionsAEA ameliorates gastric hypersensitivity in FD rats and this effect may be attributed to the improvement of sympathovagal balance.

show abstract

“…Paw volume was measured by submerging the hind paw till the tibiotarsal joint inside the water-filled Perspex cell of a plethysmometer at the same time points (37140, Ugo Basile, Comerio, Italy) [51]. …”

Section: Methodsmentioning

confidence: 99%

Toll like Receptor (TLR)-4 as a Regulator of Peripheral Endogenous Opioid-Mediated Analgesia in Inflammation

et al. 2014

View full text Add to dashboard Cite

BackgroundLeukocytes containing opioid peptides locally control inflammatory pain. In the early phase of complete Freund’s adjuvant (CFA)-induced hind paw inflammation, formyl peptides (derived e.g. from Mycobacterium butyricum) trigger the release of opioid peptides from neutrophils contributing to tonic basal antinociception. In the later phase we hypothesized that toll-like-receptor-(TLR)-4 activation of monocytes/macrophages triggers opioid peptide release and thereby stimulates peripheral opioid-dependent antinociception.ResultsIn Wistar rats with CFA hind paw inflammation in the later inflammatory phase (48–96 h) systemic leukocyte depletion by cyclophosphamide (CTX) or locally injected naloxone (NLX) further decreased mechanical and thermal nociceptive thresholds. In vitro β-endorphin (β-END) content increased during human monocyte differentiation as well as in anti-inflammatory CD14+CD16- or non-classical M2 macrophages. Monocytes expressing TLR4 dose-dependently released β-END after stimulation with lipopolysaccharide (LPS) dependent on intracellular calcium. Despite TLR4 expression proinflammatory M1 and anti-inflammatory M2 macrophages only secreted opioid peptides in response to ionomycin, a calcium ionophore. Intraplantar injection of LPS as a TLR4 agonist into the inflamed paw elicited an immediate opioid- and dose-dependent antinociception, which was blocked by TAK-242, a small-molecule inhibitor of TLR4, or by peripheral applied NLX. In the later phase LPS lowered mechanical and thermal nociceptive thresholds. Furthermore, local peripheral TLR4 blockade worsened thermal and mechanical nociceptive pain thresholds in CFA inflammation.ConclusionEndogenous opioids from monocytes/macrophages mediate endogenous antinociception in the late phase of inflammation. Peripheral TLR4 stimulation acts as a transient counter-regulatory mechanism for inflammatory pain in vivo, and increases the release of opioid peptides from monocytes in vitro. TLR4 antagonists as new treatments for sepsis and neuropathic pain might unexpectedly transiently enhance pain by impairing peripheral opioid analgesia.

show abstract

Long‐term antinociception by electroacupuncture is mediated via peripheral opioid receptors in free‐moving rats with inflammatory hyperalgesia

Cited by 24 publications

References 59 publications

CXCL10 Controls Inflammatory Pain via Opioid Peptide-Containing Macrophages in Electroacupuncture

CXCL10 Controls Inflammatory Pain via Opioid Peptide-Containing Macrophages in Electroacupuncture

Effects and mechanisms of auricular electroacupuncture on gastric hypersensitivity in a rodent model of functional dyspepsia

Toll like Receptor (TLR)-4 as a Regulator of Peripheral Endogenous Opioid-Mediated Analgesia in Inflammation

Contact Info

Product

Resources

About