Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: Enhanced function of TRPV1 via up-regulation by insulin-like growth factor-1 in a rat model of bone cancer pain.

Authors: Y Li, J Cai, Y Han, X Xiao, X L Meng, L Su, F Y Liu, G G Xing, Y Wan

Journal, date & volume: Eur J Pain, 2014 Jul , 18, 774-84

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24827675

Abstract
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.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.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.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.