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Ls.%20Similarly,%20the%20ipsilateral%20paw%20withdrawal%201-phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole1-phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole latencies responsive to the radiant thermal stimuli were also significantly shortened in the rats implanted with tumor cells, which started at day 5 throughConsidering the important role of PAR2 in neuroinflammation and the pathogenesis of several kinds of pain [12], we next determine the involvement of spinal PAR2 signaling in the induction of the enhancement of spinal glutamatergic transmission and pain behavior in the rats implanted with tumor cells. Firstly, as shown in Figure 2A, 5-tetramethyl-1 the expression of PAR2 was significantly increased in the dorsal horn of the rats with bone cancer. This indicated the potential role of PAR2 in the pathogenesis of bone cancer-induced pain.Bao et al. Molecular Pain 2014, 10:28 http://www.molecularpain.com/content/10/1/Page 3 ofFigure 1 Inhibition of BDNF signaling attenuated pain behavior in the rats with bone cancer. (A) Implantation of tumor cells (TCI) into the tibias significantly increased the protein expression of BDNF in the spinal dorsal horn of the rats (day 5: t = 3.7, P < 0.01; day 15: t = 4.7, P < 0.01; n = 7 rats in each group); (B) N,N’-Dimethyl-N-[2-(methylamino)ethyl]ethylenediamine Intrathecal injection of TrkB-Fc (1.5 g, from day 3 through day 15) attenuated the increase of input (stimuli intensity) ?output (EPSC amplitude) response in the dorsal horn neurons in the modeled rats (F(1,20) = 13.36, P < 0.01, n = 9?2 neurons per group); (C) Intrathecal injection of TrkB-Fc significantly recovered the ipsilateral paw withdrawal threshold response to mechanical (F(1, 18) = 11.24, P < 0.01) and radiant thermal stimuli (F(1, 18) = 10.85, P < 0.01) in the rats with bone cancer (n = 8?0 rats per group). Control vs. TCI: *, P < 0.05; **, P < 0.01; TCI vs. TCI + TrkB-Fc: , P < 0.05; , P < 0.01.Then, FSLLRY-NH2 (10 g, from day3 to day 15), the antagonist of PAR2, was daily delivered via the intrathecal catheter to determine its effect on BDNF function,glutamatergic strength and pain behavior in the rats with bone cancer. As shown in Figure 2B, blockade of PAR2 signaling by FSLLRY-NH2 significantly reversed theBao et al. Molecular Pain 2014, 10:28 http://www.molecularpain.com/content/10/1/Page 4 ofFigure 2 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/13867361 (See legend on next page.)Bao et al. Molecular Pain 2014, 10:28 http://www.molecularpain.com/content/10/1/Page 5 of(See figure on previous page.) Figure 2 Inhibition of PAR2 signaling attenuated pain behavior in the rats with bone cancer. (A) Implantation of tumor cells in the tibias significantly increased the expression of PAR2 in the spinal dorsal horn of the rats (day 5: t = 2.84, P < 0.05; day 15: t = 3.18, P < 0.01; n = 7 rats in each group); (B) Blockade of PAR2 signaling by FSLLRY-NH2 (10 g, from day 3 through day 15) significantly attenuated the upregulation of spinal BDNF in the rats with bone cancer pain (t = 4.21, P 0.05, n = 6? rats per group); (C) Intrathecal injection of FSLLRY-NH2 significantly attenuated the increase of input (stimuli intensity) ?output (EPSC amplitude) response in the dorsal horn neurons in the modeled rats (F(1, 21) = 10.75, P < 0.01, n = 9?2 neurons per group); (D) Intrathecal injection of FSLLRY-NH2 significantly attenuated PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/21715270 the increase of GluR1 (t = 2.57, P < 0.05) and NR2B (t = 2.40, P < 0.05) in the dorsal horn in the modeled rats (n = 6? rats per group); (E) Intrathecal injection of FSLLRY-NH2 significantly recovered the ipsilateral paw withdrawal threshold response to mechani.
