Peripheral and central antinociceptive action of Na+-K+-2Cl- cotransporter blockers on formalin-induced nociception in rats
Peripheral and central antinociceptive action of Na+-K+-2Cl- cotransporter blockers on formalin-induced nociception in rats
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DOI：
10.1016/j.pain.2004.12.023
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发表时间：
2005-03-01
期刊：
影响因子：
7.4
通讯作者：
Alvarez-Leefmans, FJ
中科院分区：
文献类型：
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作者：
Granados-Soto, V;Arguelles, CF;Alvarez-Leefmans, FJ
在大鼠福尔马林试验中，研究了Na+- k +- 2cl（-）共转运体（NKCC）抑制剂可能的局部外周和脊髓（鞘内）抗感知作用。在给予共转运蛋白抑制剂后，评估后爪注射福尔马林(M)引起的伤害性退缩行为。同侧足部局部外周预处理布美他尼（ED30, 27.1 +/- 12.7 μ g/只爪）、吡列他尼（ED30, 109.2 +/- 21.6 μ g/只爪）或呋塞米（ED30, 34.3 +/- 5.0 μ g/只爪），而非对照剂（DMSO 100%），在第2期试验中产生剂量依赖性的抗刺激作用。局部布美他尼效果最好（类似于70%的抗痛感）。布美他尼也能抑制福尔马林诱导的第一阶段退缩行为（ED30, 105.6 +/- 99.1 μ g/爪）。脊髓鞘内预处理布美他尼（ED30, 194.6 +/- 97.9 μ g）、吡列他尼（ED30, 254.4 +/- 104.9 μ g）或呋塞米（ED30, 32.0 +/- 6.9 μ g），但不包括载药（DMSO 100%），也能在第2期产生抗痛感。在这种情况下，只有鞘内速尿在第1期减少了退缩行为（ED30, 99.4 +/- 51.4 μ g），在第2期具有最大的抗伤害感受作用（类似于65%的抗伤害感受）。阿片受体拮抗剂纳洛酮（2mg /kg, s.c）不能逆转外周或脊髓给药NKCC阻滞剂诱导的抗痛觉作用。我们的数据表明，定位于椎内和外周部位感觉神经元的Na+- k +- 2cl（-）共转运体参与了福尔马林诱导的伤害感受。(c) 2004年国际疼痛研究协会。Elsevier B.V.版权所有。
The possible local peripheral and spinal (intrathecal) antinociceptive effect of Na+-K+-2Cl(-) cotransporter (NKCC) inhibitors was investigated in the rat formalin test. Nociceptive flinching behavior induced by formalin (M) injection in the hind paw was assessed following administration of cotransporter inhibitors. Local peripheral pretreatment in the ipsilateral paw with bumetanide (ED30, 27.1 +/- 12.7 mu g/paw), piretanide (ED30, 109.2 +/- 21.6 mu g/paw) or furosemide (ED30, 34.3 +/- 5.0 mu g/paw), but not vehicle (DMSO 100%), produced dose-dependent antinociception in phase 2 of the test. Local bumetanide had the greatest effect (similar to 70% antinociception). Bumetanide also inhibited formalin-induced flinching behavior during phase 1 (ED30, 105.6 +/- 99.1 mu g/paw). Spinal intrathecal pretreatment with bumetanide (ED30, 194.6 +/- 97.9 mu g), piretanide (ED30, 254.4 +/- 104.9 mu g) or furosemide (ED30, 32.0 +/- 6.9 mu g), but not vehicle (DMSO 100%), also produced antinociception in phase 2. In this case, only intrathecal furosemide reduced flinching behavior during phase 1 (ED30, 99.4 +/- 51.4 mu g) and had the maximal antinociceptive effect in phase 2 (similar to 65% antinociception). The opioid receptor-antagonist naloxone (2 mg/kg, s.c.) did not reverse antinociception induced by either peripheral or spinal administration of NKCC blockers. Our data suggest that the Na+-K+-2Cl(-) cotransporter localized in sensory neurons at intraspinal and peripheral sites is involved in formalin-induced nociception. (c) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.