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- Title
Rho/ROCK acts downstream of lysophosphatidic acid receptor 1 in modulating P2X<sub>3</sub> receptor-mediated bone cancer pain in rats.
- Authors
Jing-xiang Wu; Xiao-min Yuan; Qiong Wang; Wang Wei; Mei-ying Xu
- Abstract
Background: Lysophosphatidic acid receptor 1 and Rho/ROCK signaling is implicated in bone cancer pain development. However, it remains unknown whether the two signaling pathways function together in P2X3 receptor-mediated bone cancer pain. Results: In this study, using a rat model of bone cancer, we examined the expression of P2X3 and lysophosphatidic acid receptor 1 in rat dorsal root ganglion neurons and further dissected whether lysophosphatidic acid receptor 1 and Rho/ ROCK-mediated pathways interacted in modulating rat pain behavior. Bone cancer was established by inoculatingWalker 256 cells into the left tibia of female Wistar rats. We observed a gradual and yet significant decline in mean paw withdrawal threshold in rats with bone cancer, but not in control rats. Our immunohistochemical staining revealed that the number of P2X3- and lysophosphatidic acid receptor 1-positive dorsal root ganglion neurons was significantly greater in rats with bone cancer than control rats. Lysophosphatidic acid receptor 1 blockade with VPC32183 significantly attenuated decline in mean paw withdrawal threshold. Flinching behavior test further showed that lysophosphatidic acid receptor 1 inhibition with VPC32183 transiently but significantly attenuated α,β-meATP-induced increase in paw lift time per minute. Rho inhibition by intrathecal BoTXC3 caused a rapid reversal in decline in mean paw withdrawal threshold of rats with bone cancer. Flinching behavior test showed that BoTXC3 transiently and significantly attenuated α,β-meATP-induced increase in paw lift time per minute. Similar findings were observed with ROCK inhibition by intrathecal Y27632. Furthermore, VPC32183 and BoTXC3 effectively aborted the appearance of lysophosphatidic acid-induced calcium influx peak. Conclusions: Lysophosphatidic acid and its receptor LPAR1, acting through the Rho-ROCK pathway, regulate P2X3 receptor in the development of both mechanical and spontaneous pain in bone cancer.
- Subjects
LYSOPHOSPHATIDIC acid receptors; PURINERGIC receptors; CANCER pain treatment; CELLULAR signal transduction; LABORATORY rats
- Publication
Molecular Pain, 2016, Vol 12, p1
- ISSN
1744-8069
- Publication type
Article
- DOI
10.1177/1744806916644929