title: Association between extracellular signal-regulated kinase expression and the anti-allodynic effect in rats with spared nerve injury by applying immediate pulsed radiofrequency.
abstract: BACKGROUND
  The application of pulsed radiofrequency (PRF) close to the dorsal root ganglia, or peripheral nerves, has been demonstrated to be effective for the treatment of chronic neuropathic pain conditions. The goal of this study was to investigate the analgesic effect of immediate PRF treatment after nerve injury and its possible cellular alterations in the dorsal horn of the spinal cord in rats with spared nerve injury (SNI).
  
  
  METHODS
  Neuropathic pain was achieved in a SNI neuropathic pain model by ligating and cutting the common peroneal and tibial branches of the left sciatic nerve, leaving the sural nerve intact. Wistar rats were divided into four groups that received different treatments, i.e., SNI and PRF for 6 min at 45 V (SNI + PRF-45 V), at 60 V (SNI + PRF-60 V), SNI alone, and sham groups. After the SNI surgery, each rat was immediately given the PRF treatment (500 kHz, rate of 2 Hz, 20 ms duration, temperature below 42 °C) on the left sciatic nerve 0.3-0.4 cm proximal to the injured site. The behavioral measurements included mechanical allodynia and cold allodynia of the ipsilateral hind paw and were performed during the 28 days that followed the SNI surgery and PRF treatment. Total extracellular signal-regulated kinase 1 and 2 (ERK1/2) and phospho-ERK1/2 were measured using Western blot in the ipsilateral spinal cord from animals in the different groups.
  
  
  RESULTS
  The three groups of rats with nerve injuries manifested a lower paw withdrawal threshold (PWT) in the behavioral measurement of mechanical allodynia and a shorter painful-behavior duration in the cold allodynia test over 28 days. Mechanical allodynia measurement showed that both the PRF-45 V and PRF-60 V treatment groups exhibited a more prominent antiallodynic effect than did the SNI group from days 1 to 28 after surgery. Similarly, in comparison with the SNI group, both the SNI + PRF-45 V and SNI + PRF-60 V groups had significant inhibition on the cold allodynia measurement from days 1 to 28 after surgery. Furthermore, the activation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) in the ipsilateral spinal dorsal horn of SNI rats was effectively inhibited in the SNI + PRF-45 V and SNI + PRF-60 V groups for 28 days after surgery.
  
  
  CONCLUSIONS
  Immediate PRF application on the proximal nerve injury site provided a significant inhibition of neuropathic pain formation, accompanied by the inhibition of ERK activation.
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei, 24205, Taiwan.|Department of Anesthesiology & Integrated Pain Management Center, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan.|Department of Chemistry, Fu-Jen Catholic University and Graduate Institute of Basic Medicine, Fu-Jen Catholic University, Taipei, Taiwan.
authors.forename: Chun-Chang
authors.initials: CC
authors.lastname: Yeh
authors.affiliation: Department of Anesthesiology & Integrated Pain Management Center, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan.
authors.forename: Zhi-Fu
authors.initials: ZF
authors.lastname: Wu
authors.affiliation: Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan.
authors.forename: Jui-Chieh
authors.initials: JC
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology & Integrated Pain Management Center, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan.|Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan.
authors.forename: Chih-Shung
authors.initials: CS
authors.lastname: Wong
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei, 24205, Taiwan.|Department of Medical Research, Cathay General Hospital, Taipei, Taiwan.|Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chi-Jung
authors.initials: CJ
authors.lastname: Huang
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei, 24205, Taiwan. 034407@mail.fju.edu.tw.
authors.forename: Jinn-Shyan
authors.initials: JS
authors.lastname: Wang
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei, 24205, Taiwan. chiencmail@gmail.com.|Department of Anesthesiology, Sijhih Cathay General Hospital, New Taipei, Taiwan. chiencmail@gmail.com.|Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan. chiencmail@gmail.com.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chien
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics*; D006930:Hyperalgesia / Q000628:therapy*; D008297:Male; D009437:Neuralgia / Q000628:therapy*; D061208:Pulsed Radiofrequency Treatment / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries; D013116:Spinal Cord / Q000378:metabolism; D013497:Sural Nerve / Q000378:metabolism; D013997:Time Factors
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases