Role of ATP-sensitive potassium channels in modulating nociception in rat model of bone cancer pain.
Bone cancer pain is a major clinical problem and remains difficult to treat. ATP-sensitive potassium (KATP) channels may be involved in regulating nociceptive transmission at the spinal cord level. We determined the role of spinal KATP channels in the control of mechanical hypersensitivity in a rat model of bone cancer pain. The rat model of bone cancer pain was induced by implanting rat mammary gland carcinoma cells (Walker256) into the tibias. KATP modulators (pinacidil and glibenclamide) or the specific Kir6.2-siRNA were injected via an intrathecal catheter. The mechanical withdrawal threshold of rats was tested using von Frey filaments. The Kir6.2 mRNA and protein levels were measured by quantitative PCR and western blots, respectively. Intrathecal injection of pinacidil, a KATP channel opener, significantly increased the tactile withdrawal threshold of cancer cell-injected rats in a dose-dependent manner. In contrast, intrathecal delivery of glibenclamide, a KATP channel blocker, or the specific Kir6.2-siRNA significantly reduced the tactile withdrawal threshold of cancer cell-injected rats. The mRNA and protein levels of Kir6.2 in the spinal cord of cancer cell-injected rats were significantly lower than those in control rats. Our findings suggest that the KATP channel expression level in the spinal cord is reduced in bone cancer pain. Activation of KATP channels at the spinal level reduces pain hypersensitivity associated with bone cancer pain.
Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Hui
H
Xia
Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Dengwen
D
Zhang
Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Shijie
S
Yang
Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Yu
Y
Wang
Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Lin
L
Xu
Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Jinjing
J
Wu
Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Jing
J
Ren
Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Wenlong
W
Yao
Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Longchang
L
Fan
Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Chuanhan
C
Zhang
Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Yuke
Y
Tian
Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Hui-Lin
HL
Pan
Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: xrwang@mail.hust.edu.cn.
Xueren
X
Wang
D000818:Animals; D001859:Bone Neoplasms / Q000503:physiopathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D049990:Membrane Transport Modulators / Q000494:pharmacology; D009374:Neoplasms, Experimental; D059225:Nociception / Q000502:physiology*; D010146:Pain / Q000378:metabolism / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D020110:Pinacidil / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D014110:Touch; D000099161:Kcnj11 Channel
D005905:Glyburide; D049990:Membrane Transport Modulators; D020110:Pinacidil; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000099161:Kcnj11 Channel
ATP-sensitive potassium channel; Allodynia; Bone cancer pain; Glibenclamide; Pinacidil; Spinal cord