title: The Effects of Electroacupuncture on the Apelin/APJ System in the Spinal Cord of Rats With Inflammatory Pain.
abstract: Electroacupuncture (EA) is widely applied for pain management, but the analgesic effects of EA have not been fully elucidated. In this study, we investigated the effect of EA on inflammatory pain caused by intraplantar injection of complete Freund's adjuvant (CFA) and apelin/APJ expression in the spinal cord of rats.
  
  
  
  The study was conducted in 3 parts. In part 1, Sprague-Dawley rats were divided into 4 groups (n = 10): sham, CFA, EA (CFA + 2 Hz EA at acupoints), and NA-EA (CFA + acupuncture without electrical stimulation). The time courses of mechanical and thermal sensitivity were determined. The protein and messenger RNA (mRNA) levels of apelin and APJ in the spinal cord were assayed by Western blotting and real-time polymerase chain reaction, respectively. In part 2, the rats were divided into 5 groups (n = 7-8): sham, CFA, EA, F13A (CFA + intrathecal injection of F13A), and EA-F13A (CFA + EA + intrathecal injection of F13A). In part 3, the rats were divided into 5 groups (n = 8): sham, CFA, EA, apelin-13 (CFA + intrathecal injection of apelin-13), and EA + apelin-13 (CFA + EA + intrathecal injection of apelin-13).
  
  
  
  EA treatment exhibited significant antinociceptive effects (mechanical sensitivity: mean difference [99% confidence interval {CI}]: 5.86 [4.96-6.77]; thermal sensitivity: mean difference [99% CI]: 2.45 [0.91-4.00]; EA versus CFA) and mitigated the CFA-induced reduction of apelin and APJ protein and mRNA expression in the spinal cord. Furthermore, intrathecal injection of the apelin/APJ system antagonist F13A blocked the analgesic effect of EA (mechanical sensitivity: mean difference [99% CI]: 8.99 [5.81-12.17]; thermal sensitivity: mean difference [99% CI]: 4.22 [1.33-7.12]; EA versus EA-F13A). When EA was combined with apelin-13 through intrathecal administration, it was more potent in reducing mechanical allodynia (mean difference [99% CI]: 5.98 [2.38-9.57], EA + apelin-13 versus apelin-13; mean difference [99% CI]: 4.29 [0.72-7.87], EA + apelin-13 versus EA) and thermal hyperalgesia (mean difference [99% CI]: 5.23 [2.19-8.28], EA + apelin-13 versus apelin-13; mean difference [99% CI]: 6.43 [3.38-9.48], EA + apelin-13 versus EA).
  
  
  
  EA stimulation could alleviate inflammatory pain, at least in part, by restoring apelin and APJ mRNA and protein expression levels, which are downregulated in the CFA pain model.
authors.affiliation: From the *Laboratory of Integrative Medicine Surgery, Shu Guang Hospital Affiliated with the Shanghai University of Traditional Chinese Medicine, Shanghai, China; †College of Acumox and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, China; ‡Department of Cardiothoracic Surgery, Shu Guang Hospital Affiliated with the Shanghai University of Traditional Chinese Medicine, Shanghai, China; and §Department of Anesthesiology, Shu Guang Hospital Affiliated with the Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Ziyong
authors.initials: Z
authors.lastname: Ju
authors.forename: Yue
authors.initials: Y
authors.lastname: Yong
authors.forename: Tongyu
authors.initials: T
authors.lastname: Chen
authors.forename: Jiangang
authors.initials: J
authors.lastname: Song
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D015671:Electroacupuncture; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D059225:Nociception / Q000187:drug effects; D059226:Nociceptive Pain / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D017288:Pain Threshold / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000073861:Apelin; D000075244:Apelin Receptors; C498579:Apln protein, rat; C491284:Aplnr protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D005620:Freund's Adjuvant