Abstract

BackgroundEvidence is building steadily on the effectiveness of acupuncture therapy in pain relief and repeated acupuncture-induced pain relief is accompanied by improvement of hippocampal neural synaptic plasticity. To further test the cellular and molecular changes underlying analgesic effect of acupuncture, the global change of acupuncture associated protein profiles in the hippocampus under neuropathic pain condition was profiled.MethodsThe chronic constrictive injury (CCI) model was established by ligature of the unilateral sciatic nerve in adult Wistar rats. Rats were randomized into normal control (NC) group, CCI group, and CCI with electroacupuncture (EA) stimulation group. EA was applied to bilateral Zusanli (ST36) and Yanglingquan (GB34) in the EA group. Differentially expressed proteins in the hippocampus in the three groups were identified by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry. The functional clustering of the identified proteins was analyzed by Mascot software.ResultsAfter CCI, the thermal pain threshold of the affected hind footpad was decreased and was reversed gradually by 12 sessions of acupuncture treatment. Following EA, there were 19 hippocampal proteins identified with significant changes in expression (>2-fold), which are involved in metabolic, physiological, and cellular processes. The top three canonical pathways identified were “cysteine metabolism”, “valine, leucine, and isoleucine degradation” and “mitogen-activated protein kinase (MAPK) signaling”.ConclusionsThese data suggest that the analgesic effect of EA is mediated by regulation of hippocampal proteins related to amino acid metabolism and activation of the MAPK signaling pathway.

Highlights

  • Evidence is building steadily on the effectiveness of acupuncture therapy in pain relief and repeated acupuncture-induced pain relief is accompanied by improvement of hippocampal neural synaptic plasticity

  • We previously reported that repeated acupuncture intervention-induced pain relief in rats with chronic constrictive injury (CCI) of the sciatic nerve was accompanied by improvement of hippocampal neural synaptic plasticity and regulation of CaMKII and synaptophysin expression [15]

  • Effects of EA on pain threshold Before ligature of the sciatic nerve, there was no difference in the Difference value of PWL (PWLD) between the healthy and the affected hindlimbs in the normal control (NC), CCI, and EA groups (P > 0.05), suggesting a similar baseline thermal pain threshold in rats in the three groups (Figure 1B)

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Summary

Introduction

Evidence is building steadily on the effectiveness of acupuncture therapy in pain relief and repeated acupuncture-induced pain relief is accompanied by improvement of hippocampal neural synaptic plasticity. It is well established that acupuncture therapy is effective in relieving symptoms of patients with neuropathic pain [4,5,6]. Experimental studies have demonstrated that acupuncture intervention can effectively relieve chronic neuropathic and inflammatory pain in rats [7,8]. Acupuncture therapy is considered a better choice for pain relief due to the limited options, side effects, and insufficient analgesia of currently available drugs. We previously reported that repeated acupuncture intervention-induced pain relief in rats with chronic constrictive injury (CCI) of the sciatic nerve was accompanied by improvement of hippocampal neural synaptic plasticity and regulation of CaMKII and synaptophysin expression [15]

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