Glial Glutamate Transporter Activator, LDN‐212320, Attenuates Formalin‐Induced Pain Behavior in Mice

Abstract

Previous studies have shown that glial glutamate transporter‐1 (GLT‐1) in the hippocampus and anterior cingulate cortex (ACC) are critically involved in pain processing and modulation in the central nervous system. The objective of the present study was to investigate the role of GLT‐1 activator, 3‐[[(2‐Methylphenyl) methyl]thio]‐6‐(2‐pyridinyl)‐pyridazine (LDN‐212320), in formalin‐induced pain behavior in mice. Animal received 10 μl injection of formalin (2.5%) into the planter surface of the hind paw and the duration of licking/biting responses was measured. In addition, GLT‐1 expression and extracellular signal‐regulated kinase phosphorylation (pERK) were measured in the hippocampus and ACC using Western blot analysis. The LDN‐212320 (10 or 20 mg/kg, i.p) significantly attenuated formalin‐induced nociceptive behavior. These antinociceptive effects of LDN‐212320 were reversed by systemic administration of dihydrokianic acid (10 mg/kg, i.p), a GLT‐1 antagonist. Moreover, the LDN‐212320 (10 or 20 mg/kg, i.p) increased GLT‐1 expressions in the hippocampus and ACC. Formalin induced‐ERK phosphorylation, a molecular marker of nociception, was significantly reduced by LDN‐212320 (20 mg/kg, i.p) in the hippocampus and ACC. Overall, these results suggest that LDN‐212320 plays a critical role as antinociceptive agent by upregulating GLT‐1 expression in the hippocampus and ACC. Therefore, LDN‐212320 could be a novel therapeutic drug candidate for nociceptive pain.Support or Funding InformationSupported in part by grant from Saudi Arabian Cultural Mission, USAThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.