title: Involvement of microglia and interleukin-18 in the induction of long-term potentiation of spinal nociceptive responses induced by tetanic sciatic stimulation.
abstract: OBJECTIVE
  The present study aimed to investigate the potential roles of spinal microglia and downstream molecules in the induction of spinal long-term potentiation (LTP) and mechanical allodynia by tetanic stimulation of the sciatic nerve (TSS).
  
  
  METHODS
  Spinal LTP was induced in adult male Sprague-Dawley rats by tetanic stimulation of the sciatic nerve (0.5 ms, 100 Hz, 40 V, 10 trains of 2-s duration at 10-s intervals). Mechanical allodynia was determined using von Frey hairs. Immunohistochemical staining and Western blot were used to detect changes in glial expression of interleukin-18 (IL-18) and IL-18 receptor (IL-18R).
  
  
  RESULTS
  TSS induced LTP of C-fiber-evoked field potentials in the spinal cord. Intrathecal administration of the microglial inhibitor minocycline (200 μg/20 μL) 1 h before TSS completely blocked the induction of spinal LTP. Furthermore, after intrathecal injection of minocycline (200 μg/20 μL) by lumbar puncture 1 h before TSS, administration of minocycline for 7 consecutive days (once per day) partly inhibited bilateral allodynia. Immunohistochemistry showed that minocycline inhibited the sequential activation of microglia and astrocytes, and IL-18 was predominantly colocalized with the microglial marker Iba-1 in the spinal superficial dorsal horn. Western blot revealed that repeated intrathecal injection of minocycline significantly inhibited the increased expression of IL-18 and IL-18Rs in microglia induced by TSS.
  
  
  CONCLUSIONS
  The IL-18 signaling pathway in microglia is involved in TSS-induced spinal LTP and mechanical allodynia.
authors.affiliation: Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Chu
authors.forename: Yu-Qiu
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Zhi-Qi
authors.initials: ZQ
authors.lastname: Zhao
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D006930:Hyperalgesia / Q000378:metabolism* / Q000503:physiopathology; D020382:Interleukin-18 / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D017628:Microglia / Q000378:metabolism*; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology; D009457:Neuroglia / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053724:Receptors, Interleukin-18 / Q000378:metabolism; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D020382:Interleukin-18; D053724:Receptors, Interleukin-18; D008911:Minocycline