<p>Proteomics analysis of the amygdala in rats with CFA-induced pain aversion with electro-acupuncture stimulation</p>

Abstract

Background: Clinical patients suffering from pain usually exhibit aversion to pain-associated environments (pain aversion). Electro-acupuncture (EA) has been proven to be effective for the treatment of pain aversion in our previous studies. The amygdala could have substantial consequences on emotion and pain consolidation as well as general pain aversion behavior, however, the underlying mechanism remains unclear. Purpose: The current study was performed to investigate Isobaric tags for relative and absolute quantitation (iTRAQ) based quantitative proteomic analysis of the amygdala in rats with complete Freund's adjuvant (CFA)-induced pain aversion, and comprehensive analysis of protein expression were performed to explore the underlying mechanism by which EA affects pain aversion. Materials and methods: Inflammatory pain was induced with an intraplantar injection of 100 μL of CFA in the plantar surface of the left hind paw of the male Spragure-Dawley (SD) rats. Then the CFA-induced conditioned place aversion (C-CPA) test was performed. EA stimulation on the bilateral Zusanli and Sanyinjiao acu-points was used for 14 days and the EA stimulation frequency is 2 Hz. Based on iTRAQ-based proteomics analysis, we investigated the protein expression in the amygdala. Results: EA can increase the paw withdrawal threshold in inflammatory pain induced by noxious stimulation. A total of 6319 proteins were quantified in amygdala. Of these identified proteins, 123 were identified in the pain aversion group relative to those in the saline group, and 125 significantly altered proteins were identified in the pain aversion + EA group relative to the pain aversion group. A total of 11 proteins were found to be differentially expressed in the amygdala of pain aversion and EA-treated rats. The expression of three proteins, glyceraldehyde-3-phosphate dehydrogenase, glutamate transporter-1, and p21-activated kinase 6, were confirmed to be consistent with the results of the proteome. Conclusion: Our investigation demonstrated the possible mechanism of central nerve system by which EA intervetion on pain aversion.

Quantitative Proteomic Analysis of the Central Amygdala in Neuropathic Pain Model Rats

“…Several gene array studies and proteomics studies have been directed to investigate the genes regulated in CNS following nerve injury. A recent report by Wu et al showed effects of electro-acupuncture stimulation on protein levels in amygdala of complete Freund’s adjuvant-induced inflammatory pain model rats using iTRAQ labeling . They showed more than 100 altered proteins in the painful condition, and this proves the hypothesis that plastic changes occur in amygdala in pain conditions, albeit they used the entire amygdala rather than focusing on the CeA.…”

“…A recent report by Wu et al showed effects of electroacupuncture stimulation on protein levels in amygdala of complete Freund's adjuvant-induced inflammatory pain model rats using iTRAQ labeling. 40 They showed more than 100 altered proteins in the painful condition, and this proves the hypothesis that plastic changes occur in amygdala in pain conditions, albeit they used the entire amygdala rather than focusing on the CeA. In this study, we performed proteomics investigation of neuropathic CeA using the spinal nerve transection model in which animals developed signs of neuropathy at days 7 and 14 (group 1) and at days 3, 7, and 21 (group 2) post-transection of L5 spinal nerve.…”

Acupuncture for Psychological Disorders Caused by Chronic Pain: A Review and Future Directions

“…Consistent with these results, carpal tunnel syndrome patients responded to acupuncture with greater deactivation in the amygdala compared to healthy people ( Napadow et al, 2007 ). A preclinical investigation indicated that electroacupuncture inhibited the complete Freund’s adjuvant-induced emotional response in the conditioned place aversion test by down- or upregulating the protein expression in the amygdala of pain aversion rats ( Wu et al, 2019 ).…”

Electroacupuncture Attenuates CFA-Induced Inflammatory Pain by Regulating CaMKII

“…There is a need to identify effective therapeutic methods that have minimal side effects. According to the theory of Chinese medicine, there are hundreds of acupuncture points in the human body; acupuncture points, especially the Zusanli and Sanyinjiao points, can be stimulated to relieve pain [ 4 , 5 ]. The World Health Organization has reported that acupuncture can treat 77 diseases [ 6 ].…”