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Effects of nicotinic acetylcholine receptor positive allosteric modulator on microglia activation following lipopolysaccharide‐induced neuropathic pain
Author(s) -
Abbas Muzaffar,
Rahman Shafiqur
Publication year - 2015
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.29.1_supplement.770.14
Subject(s) - neuropathic pain , allosteric modulator , acetylcholine receptor , microglia , nicotinic agonist , nicotinic acetylcholine receptor , neuroscience , chemistry , allosteric regulation , acetylcholine , pharmacology , medicine , receptor , biology , biochemistry , inflammation
Neuropathic pain is a chronic neurological disorder characterized by hyperalgesia and allodynia. Recent studies indicate that microglia activation as measured by microglia marker‐Iba‐1 and microglia morphological changes plays a critical role in pathophysiology of neuropathic pain phenotypes. The objectives of the present study was to determine the effect of TQS, an alpha7 nAChR positive allosteric modulator, on lipopolysaccharide (LPS)‐induced neuropathic pain using hot plate, a widely used technique for hyperalgesia assessment and von Frey hair test, a widely used method for the quantification of mechanical allodynia in male mice. In addition, we investigated the effect of TQS (1 or 4 mg.kg, i.p.) on Iba‐1 expression using Western blot analysis and on microglia morphology using immunohistochemistry. Acute administration of LPS (1 mg/kg, i.p.) increased (p<0.05) the sensitivity to pain (allodynia and hyperalgesia) after 6 hours. Pretreatment of TQS (1 or 4 mg/kg, i.p.) decreased the LPS induced allodynic or hyperalgesic respose (p<0.05). TQS (1 or 4 mg/kg, i.p.) also reduced Iba‐1 expression in the hippocampus (p<0.05). Moreover, TQS decreased the LPS‐induced microglia morphological changes. These results suggest that TQS reduces LPS‐induced neuropathic pain by decreasing microglia activation through targeting alpha‐7 nAChR allosteric site. (Supported by Fulbright Foundation USA)