Spinal NKCC1 blockade inhibits TRPV1-dependent referred allodynia.
Spinal NKCC1 blockade inhibits TRPV1-dependent referred allodynia.
复制标题
DOI：
10.1186/1744-8069-3-17
复制
发表时间：
2007-06-30
期刊：
影响因子：
3.3
通讯作者：
Cervero F
中科院分区：
文献类型：
--
作者：
Pitcher MH;Price TJ;Entrena JM;Cervero F
背角水平的Na+， K+， 2Cl- I型共转运体（NKCC1）和TRPV1受体参与介导炎症损伤反应的异常性疼痛。NKCC1共转运体调节细胞内[Cl-]，从而调节神经元中GABAA受体反应的大小和极性。TRPV1受体在伤害感受器中传导多种化学和自然刺激，对炎症性痛觉过敏至关重要。在此，我们测试了脊髓NKCC1共转运蛋白和TRPV1受体在小鼠内脏痛觉过敏模型中的作用。鞘内注射NKCC1抑制剂布美他尼（BUM, 1 nmol）可抑制结肠内辣椒素注射引起的腹部异常痛。在发生异常性疼痛之前或之后4小时内注射BUM是有效的。在该模型中，TRPV1拮抗剂AMG 9810 （1 nmol）也能抑制参考异常性疼痛，这表明内源性TRPV1激动剂参与参考异常性疼痛的背角。为了支持这一建议，内源性vanilloid TRPV1激动剂narachidonoyl- dopamine （NADA， 1或10 nmol， IT）可诱发后爪卒中异常性痛，并可与AMG 9810 （1 nmol）联合治疗。NADA引起的trpv1依赖性卒中异常性疼痛似乎在功能上与NKCC1有关，因为BUM （1 nmol）也抑制NADA引起的卒中异常性疼痛。我们的研究结果表明，脊髓NKCC1和TRPV1在由内脏疼痛刺激介导的转介性异常性痛中起关键作用。此外，他们认为内源性TRPV1激动剂，在疼痛状态下在中枢神经系统中释放，可能刺激TRPV1受体的初级事件，进而在增加NKCC1活性中发挥作用，导致异常性疼痛。
The Na+, K+, 2Cl- type I cotransporter (NKCC1) and TRPV1 receptors, at the level of the dorsal horn, have been implicated in mediating allodynia in response to an inflammatory insult. The NKCC1 cotransporter regulates intracellular [Cl-] and thus the magnitude and polarity of GABAA receptor responses in neurons. TRPV1 receptors transduce diverse chemical and natural stimuli in nociceptors and are critical for inflammatory hyperalgesia. Here we have tested the role of spinal NKCC1 cotransporters and TRPV1 receptors in referred allodynia in a model of visceral hyperalgesia in mice. Intrathecal (IT) injection of the NKCC1 inhibitor bumetanide (BUM, 1 nmol) inhibited referred, abdominal allodynia evoked by an intracolonic capsaicin injection. BUM was effective when injected IT either before or up to 4 hrs after the establishment of referred allodynia. The TRPV1 antagonist AMG 9810 (1 nmol) also inhibited referred allodynia in this model suggesting the involvement of an endogenous TRPV1 agonist in the dorsal horn in referred allodynia. In support of this suggestion, the endovanilloid TRPV1 agonist, narachidonoyl- dopamine (NADA, 1 or 10 nmol, IT) evoked stroking allodynia in the hindpaw that was blocked by co-treatment with AMG 9810 (1 nmol). The TRPV1-dependent stroking allodynia caused by NADA appeared to be functionally linked to NKCC1 because BUM (1 nmol) also inhibited NADA-evoked stroking allodynia. Our findings indicate that spinal NKCC1 and TRPV1 are critical for referred allodynia mediated by a painful visceral stimulus. Moreover, they suggest that endogenous TRPV1 agonists, released in the CNS in painful conditions, might stimulate TRPV1 receptors on primary afferents that, in turn, play a role in increasing NKCC1 activity leading to allodynia.
登录
查看更多内容
影响因子：
5.3
作者：
Cui, M.;Honore, P.;Faltynek, C. R.
通讯作者：
Faltynek, C. R.
DOI：
10.1016/s0169-328x(03)00284-5
发表时间：
2003-08-19
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Galan, A;Cervero, F;Laird, JMA
通讯作者：
Laird, JMA
影响因子：
7.4
作者：
Lang, Stefanie;Klein, Thomas;Treede, Rolf-Detlef
通讯作者：
Treede, Rolf-Detlef
影响因子：
7.4
作者：
Laird, JMA;Martinez-Caro, L;Cervero, F
通讯作者：
Cervero, F
影响因子：
2.5
作者：
Lin, Q;Zou, XJ;Willis, WD
通讯作者：
Willis, WD