*2.4. P2X3 Levels in L4-6 DRG and SCDH Are Involved in Chronic Inflammatory Pain*

Previous studies demonstrated that the P2X3 agonist αβ-me ATP might induce pain hypersensitivity in rats. In this study, intraplantar injection (i.pl.) or intrathecal injection (i.t.) of αβ-me ATP can induce mechanical hyperalgesia in normal rats. Compared with the control + vehicle, the PWTs of control + i.pl. α β-me ATP, and control + i.t. α β-me ATP both decreased rapidly after αβ-me ATP administration (Figure 7B,D, *P* < 0.05). In contrast, treatment with A317491 (P2X3 antagonist) via i.pl. or i.t., significantly alleviated CFA induced mechanical hypersensitivity (Figure 7B,D). These outcomes suggested that P2X3 activation is sufficient to cause pain hypersensitivity, and that P2X3 might play essential roles in the modulation of pain signal transmission from the DRG to the spinal cord.

**Figure 7.** The effect of intraplantar injection or intrathecal injection of α β-me ATP (P2X3 agonist) and A317491 (P2X3 antagonist) on the PWT. (**A**) Schematic flow diagram of the intraplantar injection of α β-me ATP (P2X3 agonist) and A317491 (P2X3 antagonist). (**B**) The effect of intraplantar injection of α β-me ATP (P2X3 agonist) and A317491 (P2X3 antagonist) on the PWT. Data are presented as the mean ± SEM, *n* = 5. - *P* < 0.05, compared with the control + intraplantar injection (i.pl.) vehicle; ̲ *P* < 0.05, compared with the control + i.pl. α β-me ATP; ◆ *P* < 0.05, compared with the CFA + i.pl. vehicle group. (**C**) Schematic flow diagram of the intrathecal injection of α β-me ATP (P2X3 agonist) and A317491 (P2X3 antagonist). (**D**)The effect of intrathecal injection of α β-me ATP (P2X3 agonist) and A317491 (P2X3 antagonist) on the PWT. Data are presented as the mean ± SEM, *n* = 5. - *P* < 0.05, compared with the control + intrathecal injection (i.t.) vehicle; ¤ *P* <0.05, compared with the control + i.t. α β-me ATP group; -*P* < 0.05, compared with the CFA + i.t. vehicle.
