Effects of nicotinic acetylcholine receptor positive allosteric modulator in a neuropathic pain model (661.10)

Abstract

Neuropathic pain is a chronic neurological disorder characterized by hyperalgesia and allodynia. Recent evidence indicates that activation of immune system plays a critical role in the pathophysiology of neuropathic pain. Moreover, pro‐inflammatory cytokines, including TNF‐alpha has a significant role in initiation and maintenance of neuropathic pain involving alpha7 nicotinic acetylcholine receptors (nAChRs). The objective 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 in male mice. In addition, we have investigated the effect of TQS (4 mg/kg, i.p) on tumor necrosis factor‐α (TNFα) using ELISA. Acute administration of LPS (1.0 mg/kg, i.p.) increased (p<0.05) the sensitivity to pain (hyperalgesia) after 24 hours. Pretreatment of TQS (1 or 4 mg/kg, i.p.) decreased the LPS induced hyperalgesic response in a dose‐dependent manner. The effect with TQS (4 mg/kg, i.p) was significantly different from control (p<0.01). TQS (4 mg/kg, i.p) also reduced TNFα level in serum. These results suggest that TQS reduces LPS‐induced neuropathic pain by targeting alpha7 nAChR allosteric site and associated nicotinic cholinergic mechanisms.Grant Funding Source: Supported by Fulbright Foundation USA