Premium
Effects of α7 nicotinic receptor positive allosteric modulator on sodium‐potassium‐chloride co‐transporter 1 activation following lipopolysaccharide‐induced neuroinflammatory pain in mice
Author(s) -
Rahman Shafiqur,
Abbas Muzaffar
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.812.2
Subject(s) - chemistry , allosteric modulator , hyperalgesia , pharmacology , methyllycaconitine , allodynia , am251 , neuropathic pain , allosteric regulation , antagonist , receptor , nicotinic agonist , nicotinic acetylcholine receptor , medicine , biochemistry , cannabinoid receptor , nociception
Neuroinflammatory pain is a chronic neurological disorder characterized by allodynia and hyperalgesia. We have shown that 3a,4,5,9b‐tetrahydro‐4‐(1‐naphthalenyl)‐3 H ‐cyclopentan[ c ]quinoline‐8‐sulfonamide (TQS), an α7 nicotinic acetylcholine receptors (α7 nAChRs) positive allosteric modulator (PAM), reduces neuroinflammatory pain, and microglial activation in the hippocampus in mice. The objective of the present study was to determine the effects of TQS, and bumetanide (BU), sodium‐potassium‐chloride co‐transporter 1 (NKCC1) antagonist, on lipopolysaccharide (LPS)‐induced neuroinflammatory pain using von Frey hair test, a widely used method for the quantification of tactile allodynia and hot plate test, a widely used technique for thermal hyperalgesia assessment, in male mice. In addition, we examined the effects of TQS (4 mg/kg) on NKCC1 mRNA expression and p‐NKCC1 immunofluorescence in the hippocampus. TQS (4 mg/kg) significantly decreased LPS‐induced tactile allodynia and thermal hyperalgesia. In addition, co‐administration of BU (10 mg/kg) with TQS (1 mg/kg) reduced tactile allodynia and thermal hyperalgesia. Taken together, these results suggest that TQS decreases LPS‐induced neuroinflammatory pain by reducing NKCC1 activation through modulating microglial α7 nAChR allosteric site. Support or Funding Information Supported by Fulbright Foundation USA