Enhanced itch elicited by capsaicin in a chronic itch model.
Chronic itch (pruritus) is an important clinical problem. However, the underlying molecular basis has yet to be understood. The Transient Receptor Potential Vanilloid 1 channel is a heat-sensitive cation channel expressed in primary sensory neurons and involved in both thermosensation and pain, but its role in chronic itch remains elusive. Here, we for the first time revealed an increased innervation density of Transient Receptor Potential Vanilloid 1-expressing sensory fibers in the skin afflicted with chronic itch. Further analysis indicated that this phenomenon is due to an expansion of Transient Receptor Potential Vanilloid 1-expressing sensory neurons under chronic itch conditions. As a functional correlates of this neuronal expansion, we observed an enhanced neuronal responsiveness to capsaicin under the dry skin conditions. Importantly, the neuronal hypersensitivity to capsaicin results in itch, rather than pain sensation, suggesting that the up-regulated Transient Receptor Potential Vanilloid 1 underlies the pain-to-itch switch under chronic itchy conditions. The study shows that there are different mechanisms of chronic pain and itching, and Transient Receptor Potential Vanilloid 1 plays an important role in chronic itch.
College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA.
Guang
G
Yu
College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Niuniu
N
Yang
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China.
Fengxian
F
Li
College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Meijuan
M
Chen
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA.
Changxiong J
CJ
Guo
College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Changming
C
Wang
College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Danyou
D
Hu
College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Yan
Y
Yang
College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Chan
C
Zhu
College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Zhongli
Z
Wang
College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Hao
H
Shi
College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Tana
T
Gegen
College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Ming
M
Tang
College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Qian
Q
He
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA liuqi@anest.wustl.edu.
Qin
Q
Liu
College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China zongxiangtang@njutcm.edu.cn.
Zongxiang
Z
Tang
D000096:Acetone; D000818:Animals; D001522:Behavior, Animal; D002211:Capsaicin / Q000008:administration & dosage; D002908:Chronic Disease; D004195:Disease Models, Animal; D004986:Ether; D005260:Female; D007279:Injections, Subcutaneous; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010146:Pain / Q000473:pathology; D011537:Pruritus / Q000139:chemically induced* / Q000473:pathology*; D050916:TRPV Cation Channels / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000378:metabolism / Q000473:pathology; D014867:Water
D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D014867:Water; D004986:Ether; D000096:Acetone; D002211:Capsaicin
Chronic itch; Transient Receptor Potential Vanilloid 1; calcium imaging; pain