15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and Pain

It has been shown that activation of spinal RhoA/Rho kinase (ROCK) signalling pathway facilitates nociception in neuropathic and inflammatory pain, but its effects on bone cancer pain (BCP) have not previously been studied. This study was designed to examine the potential role of the spinal RhoA/ROCK signalling pathway in the development of BCP. A model for bone cancer was induced by injecting Walker 256 cells into the tibia of rats. On days 6, 9 and 15 after inoculation, the expression of spinal RhoA and ROCK2 protein levels was higher in the Walker 256 cells injected rats compared to the sham rats. On day 9, intrathecal injection of C3 exoenzyme (a RhoA inhibitor, 10 pg) significantly attenuated BCP behaviour as well as up-regulation of spinal RhoA and ROCK2 protein levels. These effects were completely abolished by intrathecal pretreatment with U-46619 (a RhoA agonist, 1.5 pg). These results suggest that the spinal RhoA/ROCK signalling pathway may be involved in the development of BCP. The findings of this study may lead to novel therapeutic strategies for prevention and/or treatment of BCP.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Bone Neoplasms; Enzyme Inhibitors; Female; Injections, Spinal; Pain; Rats; Rats, Sprague-Dawley; rho-Associated Kinases; rhoA GTP-Binding Protein; Signal Transduction; Spinal Cord; Up-Regulation