P2X7 receptor of rat dorsal root ganglia is involved in the effect of moxibustion on visceral hyperalgesia

Liu, Shuangmei; Shi, Qingming; Zhu, Qicheng; Zou, Ting; Li, Guilin; Huang, An; Wu, Bing; Peng, Li; Song, Miaomiao; Wu, Qin; Xie, Qiuyu; Lin, Weijian; Xie, Wei; Wen, Shiyao; Zhang, Zhedong; Lv, Qiulan; Zou, Lifang; Zhang, Xi; Ying, Mofeng; Li, Guodong; Liang, Shangdong

doi:10.1007/s11302-014-9439-y

Cited by 32 publications

(25 citation statements)

References 41 publications

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“…P2XRs seem to be involved in visceral pain and are directly involved in the pathophysiology of IBD, with regard to intestinal inflammation but also to dysmotility and pain. 36 In animals, several studies have also evidenced P2XRs involvement in visceral pain [37][38][39] and in accordance to our findings, in post-infectious CHS, 6 even if, in our model, the direct involvement of P2XRs in CHS need to be prove using P2XRs knockout mice or P2XRs antagonists.…”

Section: Discussionsupporting

confidence: 90%

Adherent-Invasive E. coli enhances colonic hypersensitivity and P2X receptors expression during post-infectious period

et al. 2017

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Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) are related gastrointestinal disorders characterized by abdominal pain associated with colonic hypersensitivity (CHS). Studies in humans have reported an abnormal colonization of Adherent-Invasive E. coli (AIEC) in the ileum of Crohn's disease (CD) patients associated with overexpression of the bacterial colonizing receptor CEACAM6. The aim of the present study was to investigate whether AIEC reference strain LF82 could induce intestinal impairment during infectious and/or post-infectious periods and subsequently the development of CHS. Transgenic mice overexpressing human CEACAM6 protein (TG) and their wild-type littermates were gavaged by CD-associated AIEC bacteria (reference strain LF82) or PBS for 3 d. Colonic hypersensitivity was assessed by colorectal distension (CRD) test during infectious (D4) and post-infectious periods (D21). Several markers of intestinal inflammation were monitored and the colonic expression of purinergic P2X receptors was quantified. At D4, an increased visceromotor response (VMR) to the CRD test was observed in TG mice infected with CD-associated AIEC LF82 in comparison with non-infected TG mice and persisted in a subgroup of infected animals at D21 after bacteria clearance. Increased VMR was associated with low-grade intestinal inflammation, increased intestinal permeability and expression of P2X 3, 4 and 7. This study shows that certain susceptible hosts infected with CD-associated AIEC bacteria can develop persistent CHS associated with low-grade inflammation and increased P2X receptors expression. Thus, CD-associated AIEC infection in CEACAM6 transgenic mice could be used as a novel post-infectious mouse model mimicking quiescent IBD with IBS-like symptoms such as visceral pain.

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Section: Discussionsupporting

confidence: 90%

Adherent-Invasive E. coli enhances colonic hypersensitivity and P2X receptors expression during post-infectious period

et al. 2017

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“…Visceral hypersensitivity is often seen in IBS. It has been suggested that P2X7R of rat dorsal root ganglia may play a role in the transmission of the nociceptive signal (Liu et al, 2015). Emerging evidence suggests that electroacupuncture may downregulate the expression of the P2X3R and ease the sensitivity to IBS visceral pain (Weng et al, 2015).…”

Section: Irritable Bowel Syndrome (Ibs)mentioning

confidence: 99%

Purinergic drug targets for gastrointestinal disorders

Burnstock

Christofi

2017

Current Opinion in Pharmacology

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Purinergic receptors are implicated in the pathogenesis of gastrointestinal disorders and are being explored as potential therapeutic targets. Gut inflammation releases ATP that acts on neuron, glial, epithelial and immune cells. Purinergic signalling in glia and neurons is implicated in enteric neuropathies. Inflammation activates glia to increase ATP release and alter purinergic signalling. ATP release causes neuronal death and gut motor dysfunction in colitis via a P2X7-dependent neural-glial pathway and a glial purinergic-connexin-43 pathway. The latter pathway also mediates morphine-induced constipation and gut inflammation that may differ from opioid-induced constipation (OIC). P2X7R antagonists are protective in inflammatory bowel disease (IBD) models, where as AZD9056 is questionable in CD, but is potentially beneficial for chronic abdominal pain. Drug targets under investigation for IBD, IBS and motility disorders include P2X7R, P2X3R, P2Y2R, A2A/A2BAR, enzymes and transporters.

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“…Recent studies suggest that neuron-microglia interaction mediated by purinergic receptors, and subsequently by chemokine fractalkine (FKN) and its sole receptor CX3C chemokine receptor 1 (CX3CR1), plays a pivotal role in nociceptive signal transmission [9]. In addition, it was reported that ATP-gated purinergic receptor P2X7 of the dorsal root ganglia (DRG) was involved in the analgesia effect of moxibustion in rats with chronic visceral inflammatory pain [15]. ATP and P2X3 receptor in DRGs and the spinal cord were implicated in the pain relief of electroacupuncture (EA) in rats with neuropathic pain [16,17].…”

Section: Y H Gao and Cw LI Contributed Equally To This Workmentioning

confidence: 99%

Effect of electroacupuncture on the cervicospinal P2X7 receptor/fractalkine/CX3CR1 signaling pathway in a rat neck-incision pain model

Gao

Wang

et al. 2016

Purinergic Signalling

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Increasing evidence supports that acupuncture intervention is an effective approach for intraoperative and postoperative pain. Neuron-microglia crosstalk, mediated by the purinergic P2X7 receptor (R)/fractalkine/CX3CR1 cascade in the spinal cord dorsal horn, plays a pivotal role in pain processing. However, its involvement in the analgesic effect of electroacupuncture (EA) remains unclear. In this study, a rat neck-incision pain model was established by making a longitudinal incision along the midline of the neck and subsequent repeated mechanical stimulation. EA stimulation was applied to bilateral LI18, LI4-PC6, or ST36-GB34. The thermal pain threshold, cervicospinal ATP concentration, expression levels of purinergic P2XR and P2YR subunits mRNAs, and fractalkine, CX3CR1 and p38 MAPK proteins, were detected separately. The neck incision induced strong thermal hyperalgesia and upregulation of spinal ATP within 48 h. No significant change was found in thermal hyperalgesia after a single session of EA intervention. However, a single session of EA dramatically enhanced the neck incision-induced upregulation of ATP and upregulated the expression of P2X7R, which was reversed by two sessions of EA. Two sessions of EA at bilateral LI18 or LI4-PC6 attenuated hyperalgesia significantly, accompanied with downregulation of P2X7R/fractalkine/ CX3CR1 signaling after three sessions of EA. EA stimulation of LI18 or LI4-PC6 alleviates thermal hyperalgesia in neck-incision pain rats, which may be associated with its effects in regulating the neck incision-induced increase of ATP and P2X7R and subsequently suppressing fractalkine/CX3CR1 signaling in the cervical spinal cord.

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P2X7 receptor of rat dorsal root ganglia is involved in the effect of moxibustion on visceral hyperalgesia

Cited by 32 publications

References 41 publications

Adherent-Invasive E. coli enhances colonic hypersensitivity and P2X receptors expression during post-infectious period

Adherent-Invasive E. coli enhances colonic hypersensitivity and P2X receptors expression during post-infectious period

Purinergic drug targets for gastrointestinal disorders

Effect of electroacupuncture on the cervicospinal P2X7 receptor/fractalkine/CX3CR1 signaling pathway in a rat neck-incision pain model

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