Differential proteomics analysis of the analgesic effect of electroacupuncture intervention in the hippocampus following neuropathic pain in rats

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.

Activation of hippocampal MEK1 contributes to the cumulative antinociceptive effect of electroacupuncture in neuropathic pain rats

“…We found that after CCI, MEK1 was down-regulated in the hippocampus and up-regulated in the hypothalamus. However, following 12 sessions of EA intervention, MEK1 in both regions recovered to normal levels [18, 21]. We extended that work in the present study to clarify the differential effects of multiple and single EA intervention sessions in CCI rats.…”

“…ST36 is located 5 mm beneath the capitulum fibulae and lateral posterior to the knee joint, and GB34 is approximately 5 mm superior-lateral to ST36 [18]. In the present study, the animals in the EA group were treated with bilateral ST36 and GB34.…”

“…These findings may support the notion that hippocampal formation plays an important role in both pain and EA perception. Our initial work showed that the hippocampus participated in the cumulative analgesic effect of multiple sessions of EA intervention, and many molecules in this brain region were implicated in this process [18]. Among them, mitogen-activated protein kinase kinase 1 (MEK1) signaling has warranted special attention.…”

Positive shift of Nav1.8 current inactivation curve in injured neurons causes neuropathic pain following chronic constriction injury

“…A 20 sec limit was imposed to prevent tissue damage. Each rat was assessed five times and the mean value was expressed as the thermal withdrawal latency (22). The paw withdrawal response to mechanical stimuli was measured using the Electronic von Frey Anesthesiometer (IITC Life Science Inc.).…”

NK cells mediate the cumulative analgesic effect of electroacupuncture in a rat model of neuropathic pain

“…In our previous studies, repeated EA intervention induces a cumulative effect in chronic constriction injury (CCI) rats [18–20]. The analgesic effect of EA peaked after several successive sessions of treatment.…”