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.
Keywords: Iba1; Preemptive analgesia; c-fos; formalin-induced acute inflammatory pain; inflammatory cytokines; neurotransmitters; pre-electroacupuncture.