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Role of the spinal Na+/H+ exchanger in formalin-induced nociception

Authors
Journal
Neuroscience Letters
0304-3940
Publisher
Elsevier
Publication Date
Volume
501
Issue
1
Identifiers
DOI: 10.1016/j.neulet.2011.06.048
Keywords
  • Nhe1
  • Nhe Inhibitors
  • Zoniporide
  • Nhe1 Like-Immunoreactivity
  • Spinal Processing
Disciplines
  • Biology
  • Chemistry
  • Pharmacology

Abstract

Abstract This study assessed the role of the Na+/H+ exchanger (NHE) in the formalin-induced nociception as well as the expression of the NHE isoform 1 (NHE1) in the rat spinal cord by using immunohistochemistry. Rats received a 50μl injection of diluted formalin (0.5%). Nociceptive behavior was quantified as the number of flinches of the injected paw. Intrathecal administration of the partially selective NHE1 inhibitors DMA, EIPA (0.3–30μM/rat) and the selective NHE1 inhibitor zoniporide (0.03–3μM/rat) significantly increased formalin-induced flinching behavior in a dose-dependent manner during both phases of the test. Immunohistochemical analysis of the rat lumbar spinal cord showed that NHE1 was mainly expressed in the lamina I of the dorsal horn of the spinal cord. Double immunofluorescence staining showed co-localization of NHE1 with the peptide-rich sensory nerve fiber markers, substance P and calcitonin gene-related peptide, but not with markers of neuronal cell bodies (NeuN), microglia (OX-42) or astroglia (GFAP). Collectively, these pharmacological and anatomical results suggest that spinal NHE1 plays a role in formalin-induced nociception acting as a protective protein extruding H+.

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