title: Electroacupuncture attenuates mechanical allodynia by suppressing the spinal JNK1/2 pathway in a rat model of inflammatory pain.
abstract: BACKGROUND
  Electroacupuncture (EA) has a substantial analgesic effect on inflammatory pain induced by complete Freund's adjuvant (CFA). The activation of the c-Jun N-terminal kinase 1/2 (JNK1/2) signal transduction pathway in the spinal cord is associated with inflammatory pain. However, the relationship between EA's analgesic effect and the JNK1/2 signal transduction pathway in the inflammatory pain remain unclear. In the present study, we used the established rat model of CFA-induced inflammatory pain to investigate the role of the spinal JNK1/2 pathway in EA-mediated analgesia.
  
  
  RESULTS
  We observed a decrease in paw withdrawal thresholds and an increase in paw edema at 1 and 3 days after injecting CFA into the right hindpaw. CFA, 3 days after injection, upregulated expression of phospho-c-Jun N-terminal kinase1/2 (p-JNK1/2) protein and its downstream targets, the transcriptional regulators p-c-Jun and activator protein-1 (AP-1), as well as cyclooxygenase-2 (COX-2) and the transient receptor potential vanilloid 1 (TRPV1). EA significantly alleviated CFA-induced inflammatory pain. In addition, EA reduced p-JNK1/2 protein levels and COX-2 mRNA expressions, a degree of down-regulated p-c-Jun protein level and AP-1 DNA binding activity in the spinal dorsal horn of CFA-administered animals, but it had no effect on TRPV1 mRNA expression. Furthermore, EA and the JNK inhibitor SP600125 synergistically inhibited CFA-induced hyperalgesia and suppressed the COX-2 mRNA expression in the spinal dorsal horn.
  
  
  CONCLUSIONS
  Our findings indicate that EA alleviates inflammatory pain behavior, at least in part, by reducing COX-2 expression in the spinal cord via the JNK1/2 signaling pathway. Inactivation of the spinal JNK1/2 signal transduction pathway maybe the potential mechanism of EA's antinociception in the inflammatory pain model.
authors.affiliation: Department of Neurobiology and Acupuncture Research, the 3rd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China. Electronic address: dujunying0706@163.com.
authors.forename: Jun-Ying
authors.initials: JY
authors.lastname: Du
authors.affiliation: Department of Neurobiology and Acupuncture Research, the 3rd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China. Electronic address: fangjianqiao7532@163.com.
authors.forename: Jian-Qiao
authors.initials: JQ
authors.lastname: Fang
authors.affiliation: Department of Neurobiology and Acupuncture Research, the 3rd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China. Electronic address: liangyiwww@126.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Neurobiology and Acupuncture Research, the 3rd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China. Electronic address: fangjunfan0223@163.com.
authors.forename: Jun-Fan
authors.initials: JF
authors.lastname: Fang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015671:Electroacupuncture; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000517:prevention & control; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology*; D020935:MAP Kinase Signaling System; D008297:Male; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000201:enzymology* / Q000517:prevention & control*; D017288:Pain Threshold; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000201:enzymology
chemical_list: D005620:Freund's Adjuvant; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8
keywords: Analgesia; CFA; COX-2; Electroacupuncture; Inflammatory pain; JNK1/2; c-Jun