Enhanced function of TRPV1 via up-regulation by insulin-like growth factor-1 in a rat model of bone cancer pain.
BACKGROUND
Up-regulation of transient receptor potential vanilloid subfamily, member 1 (TRPV1) is associated with the development and maintenance of cancer pain. The present study aimed to investigate the electrophysiological function of the up-regulated TRPV1 and the potential regulatory effects of insulin-like growth factor-1 (IGF-1) on TRPV1 expression in peripheral nerves in a rat model of bone cancer pain.


METHODS
A bone cancer pain model of rats was established by injecting MRMT-1 (rat mammary gland carcinoma cells) breast cancer cells into the tibia bone cavity. Thermal hyperalgesia was assessed by paw-withdrawal latency to a thermal stimulus, and mechanical allodynia was measured with von Frey monofilaments. TRPV1 and IGF-1 expression were examined with immunohistochemical staining and Western blot. TRPV1 current density of dorsal root ganglion (DRG) neurons was measured with whole-cell patch clamping recording technique.


RESULTS
Rats showed thermal hyperalgesia and mechanical allodynia 14-21 days after MRMT-1 inoculation into the tibia bone marrow. TRPV1 protein expression and its current density increased in DRG neurons. At the same time, IGF-1 expression increased in tibia bone cavity, and IGF-1 incubation increased total or membrane TRPV1 protein expression and TRPV1 current in primary cultured DRG neurons. Inhibition of IGF-1 receptors in vivo reversed mechanical allodynia and thermal hyperalgesia in rats with bone cancer pain.


CONCLUSIONS
Our results provide novel evidence for the increase of IGF-1 in tibia bone marrow, which is responsible for the up-regulation of TRPV1 expression and function in the peripheral nerves of bone cancer pain rats.
Neuroscience Research Institute, Peking University, Beijing, China.
Y
Y
Li
J
J
Cai
Y
Y
Han
X
X
Xiao
X L
XL
Meng
L
L
Su
F Y
FY
Liu
G G
GG
Xing
Y
Y
Wan
D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D006930:Hyperalgesia; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D009374:Neoplasms, Experimental; D010146:Pain / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation
D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D007334:Insulin-Like Growth Factor I