title: Systemic QX-314 Reduces Bone Cancer Pain through Selective Inhibition of Transient Receptor Potential Vanilloid Subfamily 1-expressing Primary Afferents in Mice.
abstract: The aim of this study was to determine whether systemic administration of QX-314 reduces bone cancer pain through selective inhibition of transient receptor potential vanilloid subfamily 1 (TRPV1)-expressing afferents.
  
  
  
  A mouse model of bone cancer pain was used. The authors examined the effects of bolus (0.01 to 3 mg/kg, n = 6 to 10) and continuous (5 mg kg h, n = 5) administration of QX-314 on both bone cancer pain-related behaviors and phosphorylated cyclic adenosine monophosphate response element-binding protein expression in dorsal root ganglion neurons (n = 3 or 6) and the effects of ablation of TRPV1-expressing afferents on bone cancer pain-related behaviors (n = 10).
  
  
  
  The numbers of flinches indicative of ongoing pain in QX-314-treated mice were smaller than those in vehicle-treated mice at 10 min (3 mg/kg, 4 ± 3; 1 mg/kg, 5 ± 3 vs. 12 ± 3; P < 0.001; n = 8 to 9), 24 h (3 ± 2 vs. 13 ± 3, P < 0.001), and 48 h (4 ± 1 vs. 12 ± 2, P < 0.001; n = 5 in each group) after QX-314 administration, but impaired limb use, weight-bearing including that examined by the CatWalk system, and rotarod performance indicative of movement-evoked pain were comparable. QX-314 selectively inhibited the increase in phosphorylated cyclic adenosine monophosphate response element-binding protein expression in TRPV1-positive, but not in TRPV1-negative, dorsal root ganglion neurons compared to that in the case of vehicle administration (32.2 ± 3.0% vs. 52.6 ± 5.9%, P < 0.001; n = 6 in each group). Ablation of TRPV1-expressing afferents mimicked the effects of QX-314.
  
  
  
  This study showed that systemic administration of QX-314 in mice inhibits some behavioral aspects of bone cancer pain through selective inhibition of TRPV1-expressing afferents without coadministration of TRPV1 agonists.
authors.affiliation: From the Department of Anesthesiology and Resuscitology, Shinshu University School of Medicine, Matsumoto City, Nagano, Japan (S.F., K.Y., H.M., T.K., M.K.); and Department of Pharmacy, Shinshu University Hospital, Matsumoto City, Nagano, Japan (S.Y.).
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fuseya
authors.forename: Katsumi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Minemura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamaori
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kawamata
authors.forename: Mikito
authors.initials: M
authors.lastname: Kawamata
mesh_terms: D000779:Anesthetics, Local / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001859:Bone Neoplasms / Q000150:complications* / Q000473:pathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005727:Ganglia, Spinal / Q000187:drug effects; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009068:Movement; D010146:Pain / Q000188:drug therapy* / Q000209:etiology* / Q000523:psychology; D010147:Pain Measurement / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D016474:Weight-Bearing
chemical_list: D000779:Anesthetics, Local; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C012647:QX-314; D008012:Lidocaine