Effects of nicotinic acetylcholine receptor positive allosteric modulator on microglia activation following lipopolysaccharide‐induced neuropathic pain

Abstract

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)