Systemic QX-314 Reduces Bone Cancer Pain through Selective Inhibition of Transient Receptor Potential Vanilloid Subfamily 1-expressing Primary Afferents in Mice

被引:21
作者
Fuseya, Satoshi [1 ]
Yamamoto, Katsumi [1 ]
Minemura, Hitoshi [1 ]
Yamaori, Satoshi [2 ]
Kawamata, Tomoyuki [1 ]
Kawamata, Mikito [1 ]
机构
[1] Shinshu Univ, Sch Med, Dept Anesthesiol & Resuscitol, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan
[2] Shinshu Univ Hosp, Dept Pharm, Matsumoto, Nagano, Japan
基金
日本学术振兴会;
关键词
ROOT GANGLION NEURONS; LASTING LOCAL-ANESTHESIA; NERVE-FIBERS; DISTINCT SUBPOPULATIONS; TRPV1; ANTAGONIST; SKELETAL PAIN; ION CHANNELS; MURINE MODEL; SPINAL-CORD; LIDOCAINE;
D O I
10.1097/ALN.0000000000001152
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Background: 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. Methods: 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(-1) h(-1), 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). Results: 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 elementbinding 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 TRPV1expressing afferents mimicked the effects of QX-314. Conclusion: 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.
引用
收藏
页码:204 / 218
页数:15
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