title: Intrathecal landiolol inhibits nociception and spinal c-Fos expression in the mouse formalin test.
abstract: OBJECTIVE
  The purpose of this study was to determine if intrathecal landiolol, a beta1-blocker, can modulate formalin-induced nociception and spinal c-Fos expression in mice, in the absence of anesthesia.
  
  
  METHODS
  Thirty-two mice were randomly assigned to one of four groups: the control group (n = 8) received intrathecal normal saline 10 microL, while the other three groups (n = 8 for each) received intrathecal landiolol at escalating doses of 250 microg.kg(-1), 500 microg.kg(-1) and 750 microg.kg(-1) respectively, immediately after induction of anesthesia with isoflurane. After awakening, inflammatory pain was induced by 10 microL of 5% formalin solution injected into the dorsal surface of the right hind paw. The nociceptive behaviours including licking, biting and lifting of the injected paw were cumulatively recorded as seconds of behaviours/min during phase I (0-10 min) and phase II (10-45 min). The c-Fos protein expressions in the spinal dorsal horn were detected with immunohistochemical techniques in the control and landiolol 750 microg.kg(-1) groups.
  
  
  RESULTS
  Compared to the control group, intrathecal injection of landiolol 750 microg.kg(-1) significantly decreased pain-related behaviours in phase I, while intrathecal landiolol 250 microg.kg(-1), 500 microg.kg(-1) and 750 microg.kg(-1) significantly decreased pain-related behaviours in phase II during the formalin test. The numbers of c-Fos immunoreactive nuclei in the L5 spinal dorsal horn were significantly lower in the landiolol 750 microg.kg(-1) group compared to the control group (landiolol 750 microg.kg(-1) 2.4 +/- 1.1 vs control 9.2 +/- 3.9; P < 0.01).
  
  
  CONCLUSIONS
  The present study indicates that intrathecally administered landiolol produces significant antinociceptive effects in the formalin test. Although further studies exploring the detailed mechanism are needed, these data suggest a potential role of beta1-adrenoreceptors in spinal nociceptive processing.
authors.affiliation: Department of Anaesthesiology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhao
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugawara
authors.forename: Shihiro
authors.initials: S
authors.lastname: Miura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Iijima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kashimoto
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000775:Anesthesia, Spinal; D000818:Animals; D005557:Formaldehyde; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009025:Morpholines / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D010147:Pain Measurement / Q000379:methods; D020671:Posterior Horn Cells / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D011897:Random Allocation; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D018709:Statistics, Nonparametric; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D009025:Morpholines; D016760:Proto-Oncogene Proteins c-fos; D005557:Formaldehyde; C077049:landiolol; D014508:Urea