Prokineticin 2 facilitates mechanical allodynia induced by α,β-methylene ATP in rats.
Prokineticin 2 facilitates mechanical allodynia induced by α,β-methylene ATP in rats.
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DOI：
10.1016/j.ejphar.2015.09.047
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发表时间：
2015-11
影响因子：
5
通讯作者：
Cuixia Ren;C. Qiu;X. Gan;Ting‐ting Liu;Zu-Wei Qu;Zhiguo Rao;Wang-Ping Hu
中科院分区：
文献类型：
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作者：
Cuixia Ren;C. Qiu;X. Gan;Ting‐ting Liu;Zu-Wei Qu;Zhiguo Rao;Wang-Ping Hu
前动力蛋白2（PK 2）是一种新的趋化因子，可引起大鼠后爪机械性超敏反应，但其分子机制尚不清楚。在这里，我们发现离子型P2 X受体对于PK 2诱导的机械性异常性疼痛至关重要。首先，足底注射高剂量（3或10 pmol）的PK 2显著增加了对无害机械刺激（机械异常性疼痛）的缩爪反应频率（%）。联合应用选择性P2 X受体拮抗剂TNP-ATP可抑制PK 2诱导的机械性痛觉超敏反应。第二，虽然低剂量（0.3或1 pmol）的PK 2本身并不产生异常性疼痛反应，但它显著促进了足底注射α，β-亚甲基ATP（α，β-meATP）诱发的机械性异常性疼痛。第三，PK 2浓度依赖性地增强大鼠背根神经节（DRG）神经元的α，β-meATP激活电流。PK 2受体拮抗剂PKRA和选择性PKC抑制剂GF 109203 X可阻断PK 2增强α，β-meATP诱导的机械性痛觉超敏和α，β-meATP激活电流，PK 2受体和细胞内信号转导参与了这种增强作用。这些结果表明，PK 2通过参与由伤害性神经末梢表达的皮肤P2 X受体的敏化的机制来促进α，β-meATP诱导的机械异常性疼痛。
Prokineticin 2 (PK2), a new chemokine, causes mechanical hypersensitivity in the rat hind paw, but little is known about the molecular mechanism. Here, we have found that ionotropic P2X receptor is essential to mechanical allodynia induced by PK2. First, intraplantar injection of high dose (3 or 10 pmol) of PK2 significantly increased paw withdrawal response frequency (%) to innocuous mechanical stimuli (mechanical allodynia). And the mechanical allodynia induced by PK2 was prevented by co-administration of TNP–ATP, a selective P2X receptor antagonist. Second, although low dose (0.3 or 1 pmol) of PK2 itself did not produce an allodynic response, it significantly facilitated the mechanical allodynia evoked by intraplantar injection of α,β-methylene ATP (α,β-meATP). Third, PK2 concentration-dependently potentiated α,β-meATP-activated currents in rat dorsal root ganglion (DRG) neurons. Finally, PK2 receptors and intracellular signal transduction were involved in PK2 potentiation of α,β-meATP-induced mechanical allodynia and α,β-meATP-activated currents, since the potentiation were blocked by PK2 receptor antagonist PKRA and selective PKC inhibitor GF 109203X. These results suggested that PK2 facilitated mechanical allodynia induced by α,β-meATP through a mechanism involved in sensitization of cutaneous P2X receptors expressed by nociceptive nerve endings.