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 μg, from day 3 through day 15) significantly attenuated the upregulation of spinal BDNF in the rats with bone cancer pain (t = 4.21, P < 0.01, n = 7 per group), while no change was observed in the control rats (t = 0.42, P > 0.05, n = 6–7 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 = 9–12 neurons per group); (D) Intrathecal injection of FSLLRY-NH2 significantly attenuated 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 = 6–7 rats per group); (E) Intrathecal injection of FSLLRY-NH2 significantly recovered the ipsilateral paw withdrawal threshold response to mechanical (F_{(1, 18)} = 10.04, P < 0.01) and radiant thermal stimuli (F_{(1, 18)} = 12.49, P < 0.01) in the rats with bone cancer (n = 8–10 rats per group); (F) Intrathecal injection of scrambled peptide failed to change the pain behavior in control and modeled rats (P > 0.05, n = 8–10 rats per group). Control vs. TCI: *, P < 0.05; **, P < 0.01; TCI vs. TCI + FSLLRY-NH2: ♦, P < 0.05; ♦♦, P < 0.01.