Li Y, Cai J, Han Y, Xiao X, Meng X L, Su L, Liu F Y, Xing G G, Wan Y
Neuroscience Research Institute, Peking University, Beijing, China.
Eur J Pain. 2014 Jul;18(6):774-84. doi: 10.1002/j.1532-2149.2013.00420.x. Epub 2013 Oct 29.
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.
瞬时受体电位香草酸亚家族成员1（TRPV1）的上调与癌痛的发生和维持有关。本研究旨在探讨上调的TRPV1的电生理功能以及胰岛素样生长因子-1（IGF-1）对骨癌痛大鼠模型外周神经中TRPV1表达的潜在调节作用。
通过将MRMT-1（大鼠乳腺癌细胞）乳腺癌细胞注射到胫骨骨髓腔中建立大鼠骨癌痛模型。通过对热刺激的爪退缩潜伏期评估热痛觉过敏，并用von Frey细丝测量机械性异常性疼痛。用免疫组织化学染色和蛋白质印迹法检测TRPV1和IGF-1的表达。用全细胞膜片钳记录技术测量背根神经节（DRG）神经元的TRPV1电流密度。
将MRMT-1接种到胫骨骨髓后14-21天，大鼠出现热痛觉过敏和机械性异常性疼痛。DRG神经元中TRPV1蛋白表达及其电流密度增加。同时，胫骨骨髓腔中IGF-1表达增加，IGF-1孵育增加原代培养的DRG神经元中总TRPV1或膜TRPV1蛋白表达以及TRPV1电流。体内抑制IGF-1受体可逆转骨癌痛大鼠的机械性异常性疼痛和热痛觉过敏。
我们的结果为胫骨骨髓中IGF-1的增加提供了新的证据，这导致骨癌痛大鼠外周神经中TRPV1表达和功能上调。
