The preemptive analgesia of pre-electroacupuncture in rats with formalin-induced acute inflammatory pain

Abstract

Background Electroacupuncture has been elicited to effectively alleviate the pain sensation. Preemptive analgesic effect of pre-electroacupuncture has also been suggested in recent studies, while the underlying analgesic mechanism of pre-electroacupuncture requires further investigation. This study aimed to explore the preemptive analgesia of pre-electroacupuncture in formalin-induced acute inflammatory pain model. Methods Forty rats were randomly divided into control, model, pre-electroacupuncture, and post-electroacupuncture group. Inflammatory pain model was induced via injecting 50 µl 5% formalin into the plantar surface of right hind paw, while the equal volume of saline injection in the control group. Rats in the pre-electroacupuncture group were treated with electroacupuncture at ipsilateral Zusanli (ST36) and Weizhong (BL40) acupoints (2 Hz, 1 mA) for 30 min before formalin injection, while received the same electroacupuncture treatment immediately after formalin injection in the post-electroacupuncture group. Flinching number and licking time were recorded during 60 min after formalin injection. Immunofluorescence and Western blot were used to detect the expression of ionized calcium binding adapter molecule 1 (Iba1) and c-fos in spinal cord. Moreover, enzyme-linked immunosorbent assay was applied to measure the secretion of IL-6, IFN-γ, IL-4, substance P, and calcitonin gene-related peptide in spinal cord. Results Paw flinching and licking were obviously induced by formalin injection. Iba1, c-fos, proinflammatory cytokines (IL-6 and IFN-γ), and pain neurotransmitters (substance P and calcitonin gene-related peptide) were dramatically increased in the L4-5 spinal cord after formalin injection, while anti-inflammatory cytokine IL-4 was decreased. Pre-electroacupuncture and post-electroacupuncture administration significantly attenuated formalin-induced nociceptive effects, spinal microglia and neurons activation, proinflammatory cytokines and pain neurotransmitters upregulation, and upregulated the anti-inflammatory cytokine. Furthermore, these effects of pre-electroacupuncture were more significant than that of post-electroacupuncture. Conclusions This study illustrates the potential therapeutic effect of pre-electroacupuncture against acute inflammatory pain and reveals the mechanism underlying pre-electroacupuncture mediated analgesia, thus providing a novel preemptive analgesic treatment.

<p>Electroacupuncture Regulates Pain Transition by Inhibiting the mGluR5-PKCϵ Signaling Pathway in the Dorsal Root Ganglia</p>

“…Electroacupuncture (EA) is one of the most common methods for treating pain in Chinese medical clinics and has a therapeutic effect on acute and chronic pain. 28,29 Previous studies have shown that EA can partly prevent the transition from acute to chronic pain. 30,31 However, the mechanisms underlying its preventive effect remain unclear.…”

Phosphoproteomic Profiling of Rat’s Dorsal Root Ganglia Reveals mTOR as a Potential Target in Bone Cancer Pain and Electro-Acupuncture’s Analgesia

“…In recent years, various studies have proved the efficacy of EA in BCP from animal experiments and clinical trials ( Chen et al, 2008b ; Paley et al, 2011 ; Ryu et al, 2014 ; Paley et al, 2015 ). As reported, EA at ST36 acupoint counteracted cancer pain, attenuated nociceptive effects in inflammatory pain conditions and also neuropathic pain ( Zhang et al, 2012 ; Lu et al, 2018 ; Liu et al, 2019 ). Similar analgesic effects have also been observed in BL60 ( Chang et al, 2012 ; Liang et al, 2016 ).…”

The Anti-Nociceptive Potential of Tulathromycin against Chemically and Thermally Induced Pain in Mice

“…In mice, the centrally administered aminoglycoside (neomycin > gentamicin > kanamycin) induced significant analgesia due to blocking N-type calcium channels and thus lowering the neuronal calcium availability [ 10 ]. In rats, injection of formalin into the plantar surface of right hind paw as a pain induction model has dramatically increased the level of ionized calcium-binding adapter molecule 1 as well as the proinflammatory cytokines (IL-6 and IFN-γ), and pain neurotransmitters [ 60 ]. Tilmicosin administration was also associated with calcium channel blockade [ 57 , 61 ].…”