Purinergic ATP triggers moxibustion-induced local anti-nociceptive effect on inflammatory pain model

Abstract

Purinergic signalling adenosine and its A1 receptors have been demonstrated to get involved in the mechanism of acupuncture (needling therapy) analgesia. However, whether purinergic signalling would be responsible for the local analgesic effect of moxibustion therapy, the predominant member in acupuncture family procedures also could trigger analgesic effect on pain diseases, it still remains unclear. In this study, we applied moxibustion to generate analgesic effect on complete Freund’s adjuvant (CFA)-induced inflammatory pain rats and detected the purine released from moxibustioned-acupoint by high-performance liquid chromatography (HPLC) approach. Intramuscular injection of ARL67156 into the acupoint Zusanli (ST36) to inhibit the breakdown of ATP showed the analgesic effect of moxibustion was increased while intramuscular injection of ATPase to speed up ATP hydrolysis caused a reduced moxibustion-induced analgesia. These data implied that purinergic ATP at the location of ST36 acupoint is a potentially beneficial factor for moxibustion-induced analgesia.

Grain-sized moxibustion at Zusanli (ST36) promotes hepatic autophagy in rats with hyperlipidemia by regulating the ULK1 and TFEB expression through the AMPK/mTOR signaling pathway

“…The activation of AMPK is related to ATP, ADP, and AMP and can phosphorylate TSC2 and RAPTOR and then down-regulate mTOR [ 45 ]. Additionally, mTOR can directly phosphorylate TFEB, regulate the c-terminal serine structure of TFEB to phosphorylate it, affect the transposition of TFEB, and play a role in the generation stage of the lysosome [ 46 ]. The regulation of autophagy by TFEB is mainly achieved by dephosphorylation.…”

“…The regulation of autophagy by TFEB is mainly achieved by dephosphorylation. When mTOR is inhibited, mTORC1 dissociates from the lysosome, and TFEB separates from cytoplasmic molecular chaperone 14-3-3 to dephosphorylate into the nucleus and combine with the promoter region of the target gene, which initiates the transcription of LC3 autophagy gene and lysosome synthesis [ 46 ]. Therefore, TFEB is isolated in the cytoplasm.…”

“…Therefore, TFEB is isolated in the cytoplasm. Once activated, it can translocate to the nucleus, coordinate the expression and regulation of lysosome, and participate in the gene transcription process of autophagy-lysosome (represented by LC3-TFEB) [ 46 ]. In addition, the serine/threonine kinase ULK-1 may be phosphorylated by AMPK and mTOR to regulate autophagy14.…”

“…Moxibustion can activate AMPK by affecting ATP in mice and rats [ 48 , 49 ]. Moxibustion can effectively improve the ATP level, change the energy in local and diseased areas of moxibustion in a chronic disease state, activate the AMPK expression, and stimulate a series of reactions downstream of the pathway [ 46 , 50 ]. In this study, Compound C was adopted to inhibit AMPK, and WB and qPCR methods were used to detect the expression of p-AMPK, p-mTOR, p-ULK1 protein, and mRNA in rat liver tissues.…”

Editorial: Purinergic signalling — a perspective from China

“…In the present special issue, six original articles deal with acupuncture research. These papers engage in a multitude of issues, all related to acupuncture (the role of ATP in moxibustion-induced anti-nociceptive effect on inflammatory pain [15], the involvement of P2X3 receptors (P2X3Rs) in electro-acupuncture analgesia (EAA) on bone cancer pain [16], the participation of P2X4 and P2X7Rs in EAA effects on diabetes-induced hyperalgesia [17], P2X7R involvement in EAA affecting visceral hypersensitivity of rats with irritable bowel syndrome [18], and P2Y 1 R participation in anti-depressive-like effects of EAA treatment on social isolation stress of mice [19]). A novel approach on the real-time detection of acupuncture-induced extracellular ATP mobilization at acupoints has also been described and is believed to mediate subsequent analgesia [20].…”