title: Effect of electroacupuncture on the cervicospinal P2X7 receptor/fractalkine/CX3CR1 signaling pathway in a rat neck-incision pain model.
abstract: 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.
authors.affiliation: Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: Y H
authors.initials: YH
authors.lastname: Gao
authors.affiliation: College of Acupuncture and Moxibustion and Tui-na, Hunan University of Chinese Medicine, Changsha, Hunan Province, 410208, China.|First Affiliated Hospital of Hunan Traditional Chinese Medical College, Zhuzhou, Hunan Province, 412012, China.
authors.forename: C W
authors.initials: CW
authors.lastname: Li
authors.affiliation: Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: J Y
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Moleculobiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: L H
authors.initials: LH
authors.lastname: Tan
authors.affiliation: Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: C L
authors.initials: CL
authors.lastname: Duanmu
authors.affiliation: Meridian Research Center, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: X H
authors.initials: XH
authors.lastname: Jing
authors.affiliation: College of Acupuncture and Moxibustion and Tui-na, Hunan University of Chinese Medicine, Changsha, Hunan Province, 410208, China.
authors.forename: X R
authors.initials: XR
authors.lastname: Chang
authors.affiliation: Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China. 13521898023@163.com.
authors.forename: J L
authors.initials: JL
authors.lastname: Liu
mesh_terms: D000698:Analgesia / Q000379:methods*; D000818:Animals; D000073883:CX3C Chemokine Receptor 1 / Q000378:metabolism; D002574:Cervical Vertebrae; D054428:Chemokine CX3CL1 / Q000378:metabolism; D004195:Disease Models, Animal; D015671:Electroacupuncture / Q000379:methods*; D008297:Male; D019547:Neck Pain / Q000209:etiology / Q000628:therapy*; D017288:Pain Threshold; D010149:Postoperative Pain / Q000209:etiology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000072836:Surgical Wound / Q000150:complications*
chemical_list: D000073883:CX3C Chemokine Receptor 1; C516305:CX3CR1 protein, rat; D054428:Chemokine CX3CL1; C515540:Cx3cl1 protein, rat; D058486:Receptors, Purinergic P2X7
keywords: ATP; Electroacupuncture; Fractalkine/ CX3CR1 signaling; Neck-incision pain; Neuron-microglia interaction; P2X7 receptor