Inhibition of Spinal Microglia and Astrocytes Contributes to the Anti-Allodynic Effect of Electroacupuncture in Neuropathic Pain Induced by Spinal Nerve Ligation

Liang, Yi; Qiu, Yue; Du, Junying; Liu, Jin; Fang, Jiaqi; Zhu, Jing; Fang, Jianqiao

doi:10.1136/acupmed-2015-010773

Cited by 52 publications

(41 citation statements)

References 26 publications

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“…These results suggest that, to maintain homeostasis at the early stage of neck incision, EA may suppress sFKN/CX3CR1/p38 MAPK-induced neuronalmicroglia crosstalk through regulation of ATP and its receptors in microglia. These results are similar to previous reports by Liang and colleagues that EA stimulation alleviates spinal nerve ligation-induced neuropathic pain, partially through inhibition of microglia and reduced p38 MAPK phosphorylation in rats [42,43].…”

Section: Discussionsupporting

confidence: 82%

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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Section: Discussionsupporting

confidence: 82%

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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“…Inhibition of the astrocyte activation effectively alleviates neuropathic pain induced by spinal nerve ligation in rats. 18 In the present study, CCI resulted in an up-regulation of GFAP protein in the spinal cord, accompanied by an increased number of GFAP-labeled astrocytes in the damaged tissues. It is possible that inhibition of activated astrocytes may contribute to neuropathic pain relief through suppressing the secretion of proinflammatory cytokines.…”

Section: Astrocyte Activation Contributes To Central Sensitization Ansupporting

confidence: 53%

Kindlin-1 Regulates Astrocyte Activation and Pain Sensitivity in Rats With Neuropathic Pain

Zhao

Pan

2018

Regional Anesthesia and Pain Medicine

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“…Hence, novel strategies targeting neuropathic pain are much needed clinically. Indeed, non-pharmacological approaches, such as transcutaneous electrical nerve stimulation [5], transcranial magnetic stimulation [6], and electro acupuncture [7] have been proven to significantly alleviate neuropathic pain. Nevertheless, the long-term efficacy of these approaches is yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

Hyperbaric oxygen attenuates neuropathic pain and reverses inflammatory signaling likely via the Kindlin-1/Wnt-10a signaling pathway in the chronic pain injury model in rats

Zhao

Pan

2017

J Headache Pain

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BackgroundHyperbaric oxygen (HBO) therapy is proven to attenuate neuropathic pain in rodents. The goal of the present study was to determine the potential involvement of the Kindlin-1/Wnt-10a signaling pathway during astrocyte activation and inflammation in a rodent model of neuropathic pain.MethodsRats were assigned into sham operation, chronic constriction injury (CCI), and CCI + HBO treatment groups. Neuropathic pain developed in rats following CCI of the sciatic nerve. Rats in the CCI + HBO group received HBO treatment for five consecutive days beginning on postoperative day 1. The mechanical withdrawal threshold (MWT) and the thermal withdrawal latency (TWL) tests were performed to determine mechanical and heat hypersensitivity of animals, respectively. Kindlin-1, Wnt-10a and β-catenin protein expression was examined by immunohistochemistry and Western blot analysis. Expression of tumor necrosis factor (TNF)-α was also determined by ELISA.ResultsOur findings demonstrated that HBO treatment significantly suppressed mechanical and thermal hypersensitivity in the CCI neuropathic pain model in rats. HBO therapy significantly reversed the up-regulation of Kindlin-1 in dorsal root ganglia (DRG), spinal cord, and hippocampus of CCI rats. CCI-induced astrocyte activation and increased levels of TNF-α were efficiently reversed by HBO (P < 0.05 vs. CCI). HBO also reversed Wnt-10a up-regulation induced by CCI in the DRG, spinal cord, and hippocampus (P < 0.05 vs. CCI).ConclusionsOur findings demonstrate that HBO attenuated CCI-induced rat neuropathic pain and inflammatory responses, possibly through regulation of the Kindlin-1/Wnt-10a signaling pathway.

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Inhibition of Spinal Microglia and Astrocytes Contributes to the Anti-Allodynic Effect of Electroacupuncture in Neuropathic Pain Induced by Spinal Nerve Ligation

Abstract: EA stimulation alleviates SNL-induced neuropathic pain, at least in part through inhibition of spinal glial activation. Moreover, inhibition of spinal microglia and astrocyte activation may contribute to the immediate effects and maintenance of EA analgesia, respectively.

Cited by 52 publications

References 26 publications

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

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

Kindlin-1 Regulates Astrocyte Activation and Pain Sensitivity in Rats With Neuropathic Pain

Hyperbaric oxygen attenuates neuropathic pain and reverses inflammatory signaling likely via the Kindlin-1/Wnt-10a signaling pathway in the chronic pain injury model in rats

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