title: Systemic clonidine activates neurons of the dorsal horn, but not the locus ceruleus (A6) or the A7 area, after a formalin test: the importance of the dorsal horn in the antinociceptive effects of clonidine.
abstract: OBJECTIVE
  In order to clarify the principal site for the antinociceptive effects of clonidine, we investigated the nociceptive behavior and neural activity (c-fos staining) of the dorsal horn (DH), locus ceruleus (LC), and A7 area after a formalin test in normal saline- or clonidine-injected rats.
  
  
  METHODS
  Thirty-six rats were divided into 6 groups as follows: formalin test + saline (FS); formalin test + clonidine (1 mg.kg(-1)) (FC1); formalin test + clonidine (10 mg.kg(-1)) (FC10); saline (S); clonidine (1 mg.kg(-1)) (C1); and clonidine (10 mg.kg(-1)) (C10). Normal saline or clonidine was injected intraperitoneally 30 min before the formalin test. In the FS, FC1, and FC10 groups, 10% formalin was injected into the left rear paw. All rats were killed 2.5 h after normal saline or clonidine injection. Sections of the lumbar spinal cord, LC, and A7 area were processed for c-fos immunohistochemistry using the avidin-biotin peroxidase complex method. To evaluate the sedative effects of clonidine, we investigated the loss of righting reflex (LORR) for 90 min in 6 other rats as follows: clonidine (1 mg.kg(-1)) (n = 3) and clonidine (10 mg.kg(-1)) (n = 3).
  
  
  RESULTS
  The FC10 group showed fewer nociceptive behaviors and higher c-fos expression in the DH, but not in the A7 area, as well as lower c-fos expression in the LC than rats in the FS and FC1 groups (P < 0.05). The C10 group showed lower c-fos expression in the LC than that of rats in the S and C1 groups (P < 0.05). No rats exhibited LORR.
  
  
  CONCLUSIONS
  The antinociceptive effects of clonidine might be mediated primarily by neural activity in the DH.
authors.affiliation: Department of Anesthesiology, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, Tsukuba University, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Fukuda
authors.forename: Hajime
authors.initials: H
authors.lastname: Furukawa
authors.forename: Setsuji
authors.initials: S
authors.lastname: Hisano
authors.forename: Hidenori
authors.initials: H
authors.lastname: Toyooka
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010147:Pain Measurement; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D003000:Clonidine