Peripheral and central antinociceptive action of Na +–K +–2Cl − cotransporter blockers on formalin-induced nociception in rats
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 (1%) injection in the hind paw was assessed following administration of cotran...
Gespeichert in:
Veröffentlicht in: | Pain (Amsterdam) 2005-03, Vol.114 (1), p.231-238 |
---|---|
Hauptverfasser: | , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | 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 (1%) injection in the hind paw was assessed following administration of cotransporter inhibitors. Local peripheral pretreatment in the ipsilateral paw with bumetanide (ED
30, 27.1±12.7
μg/paw), piretanide (ED
30, 109.2±21.6
μg/paw) or furosemide (ED
30, 34.3±5.0
μg/paw), but not vehicle (DMSO 100%), produced dose-dependent antinociception in phase 2 of the test. Local bumetanide had the greatest effect (∼70% antinociception). Bumetanide also inhibited formalin-induced flinching behavior during phase 1 (ED
30, 105.6±99.1
μg/paw). Spinal intrathecal pretreatment with bumetanide (ED
30, 194.6±97.9
μg), piretanide (ED
30, 254.4±104.9
μg) or furosemide (ED
30, 32.0±6.9
μg), but not vehicle (DMSO 100%), also produced antinociception in phase 2. In this case, only intrathecal furosemide reduced flinching behavior during phase 1 (ED
30, 99.4±51.4
μg) and had the maximal antinociceptive effect in phase 2 (∼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. |
---|---|
ISSN: | 0304-3959 1872-6623 |
DOI: | 10.1016/j.pain.2004.12.023 |