Behavioral phenotypes of mice lacking purinergic P2X4 receptors in acute and chronic pain assays.
Behavioral phenotypes of mice lacking purinergic P2X4 receptors in acute and chronic pain assays.
复制标题
DOI：
10.1186/1744-8069-5-28
复制
发表时间：
2009-06-11
期刊：
影响因子：
3.3
通讯作者：
Inoue K
中科院分区：
文献类型：
--
作者：
Tsuda M;Kuboyama K;Inoue T;Nagata K;Tozaki-Saitoh H;Inoue K
越来越多的证据表明，P2 X受体（P2 XRs），一个由细胞外ATP激活的配体门控阳离子通道家族，在疼痛信号传导中发挥重要作用。与已被广泛研究的P2 X3 R亚型的作用相反，七种P2 XR亚型（P2 X1 R-P2 X7 R）中其他亚型的确切作用仍有待确定，因为缺乏足够强大的工具来特异性地阻断体内P2 XR信号传导。在本研究中，我们研究了一系列急性和慢性疼痛试验中p2 rx 4基因被破坏的小鼠的行为表型。虽然与野生型小鼠相比，p2 rx 4-/-小鼠在急性伤害性刺激和局部组织损伤引起的疼痛反应或运动功能方面没有表现出重大缺陷，但这些小鼠在两种慢性疼痛模型（炎症性和神经性疼痛）中表现出疼痛反应降低。在足底注射完全弗氏佐剂（CFA）建立的慢性炎性疼痛模型中，p2 rx 4-/-小鼠表现出对无害机械刺激（触觉异常性疼痛）的疼痛超敏反应减弱，以及CFA诱导的后爪肿胀减弱。在神经性疼痛的测试中观察到最引人注目的表型：由脊神经损伤引起的触觉异常性疼痛在p2 rx 4-/-小鼠中显著减弱。相比之下，在野生型和p2 rx 4-/-小鼠中，损伤后对冷刺激的疼痛超敏反应（冷异常性疼痛）是相当的。总之，这些发现揭示了P2 X4 R对神经损伤诱导的触觉异常性疼痛的主要贡献，以及在较小程度上对外周炎症的贡献。P2 X4 R的缺失在急性生理性疼痛或组织损伤引起的疼痛中没有产生缺陷，突出了阻断P2 X4 R在治疗慢性疼痛，特别是神经损伤后的触觉异常性疼痛中的治疗益处的可能性。
A growing body of evidence indicates that P2X receptors (P2XRs), a family of ligand-gated cation channels activated by extracellular ATP, play an important role in pain signaling. In contrast to the role of the P2X3R subtype that has been extensively studied, the precise roles of others among the seven P2XR subtypes (P2X1R-P2X7R) remain to be determined because of a lack of sufficiently powerful tools to specifically block P2XR signaling in vivo. In the present study, we investigated the behavioral phenotypes of a line of mice in which the p2rx4 gene was disrupted in a series of acute and chronic pain assays. While p2rx4-/- mice showed no major defects in pain responses evoked by acute noxious stimuli and local tissue damage or in motor function as compared with wild-type mice, these mice displayed reduced pain responses in two models of chronic pain (inflammatory and neuropathic pain). In a model of chronic inflammatory pain developed by intraplantar injection of complete Freund's adjuvant (CFA), p2rx4-/- mice exhibited attenuations of pain hypersensitivity to innocuous mechanical stimuli (tactile allodynia) and also of the CFA-induced swelling of the hindpaw. A most striking phenotype was observed in a test of neuropathic pain: tactile allodynia caused by an injury to spinal nerve was markedly blunted in p2rx4-/- mice. By contrast, pain hypersensitivity to a cold stimulus (cold allodynia) after the injury was comparable in wild-type and p2rx4-/- mice. Together, these findings reveal a predominant contribution of P2X4R to nerve injury-induced tactile allodynia and, to the lesser extent, peripheral inflammation. Loss of P2X4R produced no defects in acute physiological pain or tissue damaged-induced pain, highlighting the possibility of a therapeutic benefit of blocking P2X4R in the treatment of chronic pain, especially tactile allodynia after nerve injury.
登录
查看更多内容
影响因子：
7.3
作者：
Tsuda, M;Ueno, S;Inoue, K
通讯作者：
Inoue, K
DOI：
10.1073/pnas.252537299
发表时间：
2002-12-24
影响因子：
11.1
作者：
Jarvis, MF;Burgard, EC;Faltynek, C
通讯作者：
Faltynek, C
影响因子：
64.8
作者：
Souslova, V;Cesare, P;Wood, JN
通讯作者：
Wood, JN
影响因子：
3.3
作者：
Keller AF;Beggs S;Salter MW;De Koninck Y
通讯作者：
De Koninck Y
影响因子：
7.4
作者：
Flatters, SJL;Bennett, GJ
通讯作者：
Bennett, GJ