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. CONCLUSION: 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.
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. CONCLUSION: 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 painrats.
Authors: Yan Li; Hongmei Zhang; Alyssa K Kosturakis; Ryan M Cassidy; Haijun Zhang; Ross M Kennamer-Chapman; Abdul Basit Jawad; Cecilia M Colomand; Daniel S Harrison; Patrick M Dougherty Journal: Brain Behav Immun Date: 2015-06-09 Impact factor: 7.217
Authors: Yan Li; Robert Y North; Laurence D Rhines; Claudio Esteves Tatsui; Ganesh Rao; Denaya D Edwards; Ryan M Cassidy; Daniel S Harrison; Caj A Johansson; Hongmei Zhang; Patrick M Dougherty Journal: J Neurosci Date: 2017-12-18 Impact factor: 6.167
Authors: Yan Li; Pavel Adamek; Haijun Zhang; Claudio Esteves Tatsui; Laurence D Rhines; Petra Mrozkova; Qin Li; Alyssa K Kosturakis; Ryan M Cassidy; Daniel S Harrison; Juan P Cata; Kenneth Sapire; Hongmei Zhang; Ross M Kennamer-Chapman; Abdul Basit Jawad; Andre Ghetti; Jiusheng Yan; Jiri Palecek; Patrick M Dougherty Journal: J Neurosci Date: 2015-09-30 Impact factor: 6.167