Electroacupuncture ameliorates mechanical hypersensitivity by down-regulating spinal Janus kinase 2/signal transducer and activation of transcription 3 and interleukin 6 in rats with spared nerve injury

Abstract

Background: Evidence shows that the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway participates in the pathogenesis of neuropathic pain. Our previous study revealed that electroacupuncture (EA) attenuated neuropathic pain via activation of alpha-7 nicotinic acetylcholine receptor (α7nAChR) in the spinal cord. However, whether 2 Hz EA alleviates neuropathic pain by regulating the downstream molecules JAK2/STAT3 has not been fully clarified. Methods: Paw withdrawal threshold (PWT) was used as a marker of mechanical allodynia in rats with spared nerve injury (SNI). After applying 2 Hz EA on day 3, 7, 14 and 21 post-surgery, spinal expression of JAK2, STAT3 and pro-inflammatory cytokine interleukin (IL)-6 was examined using quantitative reverse transcription and real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Intrathecal injection of the α7nAChR antagonist alpha-bungarotoxin (α-Bgtx) was used to further explore the mechanism underlying the effects of 2 Hz EA on expression of JAK2/STAT3 in SNI rats. Results: It was found that levels of spinal STAT3 and IL-6 mRNA, as well as levels of phosphorylated (p)-JAK2, p-STAT3 and IL-6 protein, were markedly increased in SNI rats. 2 Hz EA attenuated the SNI-induced up-regulation of p-JAK2, p-STAT3 and IL-6 expression in the spinal cord. Furthermore, intrathecal injection of α-Bgtx (1.0 μg/kg) not only inhibited the effect of 2 Hz EA on mechanical hypersensitivity but also ameliorated the down-regulation of p-JAK2, p-STAT3 and IL-6 expression induced by 2 Hz EA. Conclusion: This study revealed that 2 Hz EA attenuated SNI-induced mechanical hypersensitivity and the concomitant up-regulation of spinal JAK2, STAT3 and IL-6 in SNI rats, suggesting that suppression of the JAK2/STAT3 signaling pathway might be the mechanism underlying the therapeutic effect of 2 Hz EA on neuropathic pain.

The Anti-Inflammatory Actions and Mechanisms of Acupuncture from Acupoint to Target Organs via Neuro-Immune Regulation

“…EA at ST36 and SP6 alleviates SNI-induced mechanical hypersensitivity, possibly via the activation of α7nAChR, inhibition of the JAK2/STAT3 pathway, and down-regulation of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in the DRG or spinal cord. 142 , 143 …”

“…EA at ST36 and SP6 alleviates SNI-induced mechanical hypersensitivity, possibly via the activation of α7nAChR, inhibition of the JAK2/STAT3 pathway, and down-regulation of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in the DRG or spinal cord. 142,143 In the respiratory system, acupuncture exerts the opposite effect on the regulation of the cholinergic system. [144][145][146][147] It is well known that ACh is a major transmitter of parasympathetic nerve fibers, which innervate the glands and smooth muscles of the airway.…”

Ropivacaine with intraspinal administration alleviates preeclampsia-induced kidney injury via glycocalyx /alpha 7 nicotinic acetylcholine receptor pathway

“…In addition, α7nAChR and its involved cholinergic anti-inflammatory pathway connect the nervous system and immune response system through the vagus nerve. For instance, α7nAChR was triggered by electroacupuncture in the spinal cord [ 37 ]. In our previous studies, α7nAChR expression in placental tissue was significantly up-regulated in the group with intraspinal labor analgesia of ropivacaine injection [ 15 , 16 ].…”

Role of nerve signal transduction and neuroimmune crosstalk in mediating the analgesic effects of acupuncture for neuropathic pain

“…It has been shown that EA upregulated α7nAChR in the L4-L6 spinal cord, thereby, upregulating GABA, 5-HT, etc. expression to reduce SNI-induced mechanical hypersensitivity (29).…”