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Antihyperalgesic and antiallodynic effects of 3a,4,5,9b‐Tetrahydro‐4‐(1‐naphthalenyl)‐3 H ‐cyclopentan[ c ]quinoline‐8‐sulfonamide in an animal model of neuroinflammatory pain
Author(s) -
Abbas Muzaffar,
Rahman Shafiqur
Publication year - 2016
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.30.1_supplement.927.1
Subject(s) - methyllycaconitine , hyperalgesia , pharmacology , chemistry , allodynia , allosteric modulator , neuropathic pain , agonist , medicine , nicotinic acetylcholine receptor , nicotinic agonist , receptor , nociception , biochemistry
Neuroinflammatory pain is a chronic neurological disorder characterized by allodynia and hyperalgesia. We have shown that microglial alpha‐7 nicotinic acetylcholine receptors (α7 nAChRs) in the hippocampus is involved in pain production and maintenance. The objective of the present study was to determine the effects of 3a,4,5,9b‐Tetrahydro‐4‐(1‐naphthalenyl)‐3 H ‐cyclopentan[ c ]quinoline‐8‐sulfonamide (TQS), an alpha7 nAChR positive allosteric modulator, and methyllycaconitine (MLA), an α7 nAChR antagonist, on lipopolysaccharide (LPS)‐induced neuroinflammatory pain using von Frey hair test, a widely used method for the quantification of mechanical allodynia and hot plate test, a widely used technique for hyperalgesia assessment in mice. In addition, we examined the effects of TQS (1 or 4 mg.kg) on ionized calcium‐binding adapter molecule‐1 (Iba‐1), a microglial activation marker. Acute administration of LPS (1 mg/kg, i.p.) increased (p<0.05) the sensitivity to pain (allodynia and hyperalgesia) after 6 hours. TQS (0.25, 1 or 4 mg/kg, i.p.) decreased LPS‐induced allodynic or hyperalgesic response (p<0.05). Pretreatment of MLA reversed TQS‐induced antiallodynic and antihypergesic effects. TQS (1 or 4 mg/kg, i.p.) also reduced the expression of Iba‐1 in the hippocampus. Taken together, these results suggest that TQS decreases LPS‐induced neuroinflammatory pain by reducing hippocampal microglial activation through modulating α7 nAChR allosteric site. Support or Funding Information Fulbright Foundation, USA