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

Gao, Yonghui; Li, C. W.; Wang, J. Y.; Tan, Lian-Hong; Duanmu, C. L.; Jing, Xiang-Hong; Chang, Xiao-Rong; Liu, J. L.

doi:10.1007/s11302-016-9552-1

Cited by 34 publications

(21 citation statements)

References 37 publications

(43 reference statements)

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“…These results are consistent with our previous studies. 18,19,35,36 GABA has a vital role in the process of pain control 37,38 and EA analgesia in the spinal cord. GABA-A and GABA-B are two receptors involved in mediating incision-induced hyperalgesia.…”

Section: Discussionmentioning

confidence: 99%

“…Our past studies revealed that the analgesic effect of EA of LI18 and LI4-PC6 is realized by upregulating levels of GABA-Aα2 and GABA-B1 mRNAs and proteins (expressed on SP-positive large and medium size neurons and satellite glial cells, respectively) in cervical DRGs, 20 , 21 down-regulating levels of mGluR5, 18 SP-NK1 signaling 19 and activities of astrocytes and microglia cells in spinal DHs. 35 , 46 It is thus deduced that EA stimulation triggers release of GABA from the presynaptic endings, then acts on GABA-A and GABA-B receptors at both pre-synaptic endings and post-synaptic membranes of GABAergic interneurons to suppress activities of glutamatergic neurons, astrocytes, etc., inducing pain relief at last in incisional neck pain rats.…”

Section: Discussionmentioning

confidence: 99%

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<p>GABAergic Inhibition of Spinal Cord Dorsal Horns Contributes to Analgesic Effect of Electroacupuncture in Incisional Neck Pain Rats</p>

Wang¹,

Bai²,

Gao³

et al. 2020

JPR

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Background: Acupuncture has shown to be effective in relieving post-surgical pain. Nonetheless, its underlying mechanisms remain largely unknown. In the present study, we investigated the effect of electroacupuncture (EA) on the expression of GABA, GABA-A receptor (R) and GABA-BR in the spinal cord dorsal horns (DHs), and the involved neural cells in rats with incisional neck pain. Materials and Methods: Male SD rats were randomly divided into control, model, Futu (LI18), Hegu-Neiguan (LI4-PC6), and Zusanli-Yanglingquan (ST36-GB34) groups. The incisional neck pain model was established by making a longitudinal incision and repeated mechanical separation along the thyroid gland region. EA (2Hz/100Hz, 1mA) was applied to LI18, LI4-PC6, ST36-GB34 separately for 30min, once at 4, 24 and 48h after incision. The local thermal pain threshold (TPT) of the focus was measured and the expression of GABA, and GABAR proteins and mRNAs detected by immunofluorescence stain and quantitative RT-PCR, respectively. Results: The analgesic effect of LI18 and LI4-PC6 was superior to that of ST36-GB34 in incisional neck pain rats. Moreover, the EA stimulation of LI18 or LI4-PC6 increased the expression of GABA and GABA-Aα2 and GABA-Aβ3, GABA-B1, and GABA-B2 mRNAs in spinal DHs 4h after surgery, while GABA-A and GABA-B antagonists inhibited the analgesic effect of LI18. Immunofluorescence double staining showed that GABA was expressed on astrocytes and neurons, and GABA-B expressed only on neurons. Conclusion: EA of both LI18 and LI4-PC6 has a good analgesic effect in incisional neck pain rats, which is closely related to their effects in upregulating the expression of GABA and its receptors in spinal DHs. The effects of LI18 and LI4-PC6 EA are obviously better that those of ST36-GB34 EA, and GABA is expressed on neurons and astrocytes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

<p>GABAergic Inhibition of Spinal Cord Dorsal Horns Contributes to Analgesic Effect of Electroacupuncture in Incisional Neck Pain Rats</p>

Wang¹,

Bai²,

Gao³

et al. 2020

JPR

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“…EA has been used to treat a variety of diseases and symptoms, including pain. Recent studies, including our own, have shown that EA can increase the paw withdrawal threshold (PWT) in inflammatory pain and neuropathic pain induced by noxious stimulation [ 9 – 12 ]. In recent years, the mechanism and treatment of psychiatric disorders associated with chronic pain have received increasing attention.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Electroacupuncture on PKMzeta in the ACC in Regulating Anxiety-Like Behaviors in Rats Experiencing Chronic Inflammatory Pain

Fang

Chen

et al. 2017

Neural Plasticity

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Chronic inflammatory pain can induce emotional diseases. Electroacupuncture (EA) has effects on chronic pain and pain-related anxiety. Protein kinase Mzeta (PKMzeta) has been proposed to be essential for the maintenance of pain and may interact with GluR1 to maintain CNS plasticity in the anterior cingulate cortex (ACC). We hypothesized that the PKMzeta-GluR1 pathway in the ACC may be involved in anxiety-like behaviors of chronic inflammatory pain and that the mechanism of EA regulation of pain emotion may involve the PKMzeta pathway in the ACC. Our results showed that chronic inflammatory pain model decreased the paw withdrawal threshold (PWT) and increased anxiety-like behaviors. The protein expression of PKCzeta, p-PKCzeta (T560), PKMzeta, p-PKMzeta (T560), and GluR1 in the ACC of the model group were remarkably enhanced. EA increased PWT and alleviated anxiety-like behaviors. EA significantly inhibited the protein expression of p-PKMzeta (T560) in the ACC, and only a downward trend effect for other substances. Further, the microinjection of ZIP remarkably reversed PWT and anxiety-like behaviors. The present study provides direct evidence that the PKCzeta/PKMzeta-GluR1 pathway is related to pain and pain-induced anxiety-like behaviors. EA treatment both increases pain-related somatosensory behavior and decreases pain-induced anxiety-like behaviors by suppressing PKMzeta activity in the ACC.

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“…This manipulation at the same time suppressed the overexpression of the two inflammatory cytokines, interleukin-1β (IL-1β) and IL-18. Further, in the neck incision pain model, both the levels of ATP and the expression of P2X7R mRNA and protein were upregulated in the spinal cord [54]. Both effects could be antagonized by EAP applied to the acupoints Zusanli and Yanglinquan.…”

Section: P2x7 Receptorsmentioning

confidence: 90%

Purinergic signaling as a basis of acupuncture-induced analgesia

Tang

et al. 2020

Purinergic Signalling

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This review summarizes experimental evidence indicating that purinergic mechanisms are causally involved in acupuncture (AP)-induced analgesia. Electroacupuncture (EAP) and manual AP release at pain-relevant acupoints ATP which may activate purinergic P2X receptors (Rs) especially of the P2X3 type situated at local sensory nerve endings (peripheral terminals of dorsal root ganglion [DRG] neurons); the central processes of these neurons are thought to inhibit via collaterals of ascending dorsal horn spinal cord neurons, pain-relevant pathways projecting to higher centers of the brain. In addition, during AP/EAP non-neuronal P2X4 and/or P2X7Rs localized at microglial cells of the CNS become activated at the spinal or supraspinal levels. In consequence, these microglia secrete bioactive compounds such as growth factors, cytokines, chemokines, reactive oxygen, and nitrogen species, which modulate the ascending neuronal pathways conducting painful stimuli. Alternatively, ATP released at acupoints by AP/EAP may be enzymatically degraded to adenosine, stimulating in loco presynaptic A1Rs exerting an inhibitory influence on the primary afferent fibers (the above mentioned pain-sensing peripheral terminals of DRG neurons) which thereby fail to conduct action potentials to the spinal cord dorsal horn. The net effect of the stimulation of P2X3, P2X4, P2X7, and A1Rs by the AP/EAP-induced release of ATP/adenosine at certain acupoints will be analgesia.

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

Cited by 34 publications

References 37 publications

<p>GABAergic Inhibition of Spinal Cord Dorsal Horns Contributes to Analgesic Effect of Electroacupuncture in Incisional Neck Pain Rats</p>

<p>GABAergic Inhibition of Spinal Cord Dorsal Horns Contributes to Analgesic Effect of Electroacupuncture in Incisional Neck Pain Rats</p>

The Effect of Electroacupuncture on PKMzeta in the ACC in Regulating Anxiety-Like Behaviors in Rats Experiencing Chronic Inflammatory Pain

Purinergic signaling as a basis of acupuncture-induced analgesia

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