title: AMPAkines have novel analgesic properties in rat models of persistent neuropathic and inflammatory pain.
abstract: BACKGROUND
  Novel analgesics that do not suppress the respiratory drive are urgently needed. Glutamate signaling through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors plays important roles in central pain circuits. AMPAkines augment AMPA receptor function and have been shown to stimulate the respiratory drive to oppose opioid-induced hypoventilation. However, their role in chronic pain states remains unknown.
  
  
  METHODS
  The authors studied AMPAkines (CX546 and CX516) in rat spared nerve injury (SNI) model of neuropathic pain and Complete Freund's Adjuvant (CFA) model of inflammatory pain. They measured the effect of AMPAkines on mechanical and cold allodynia. They also evaluated their effect on depressive symptoms of pain using the forced swim test, as time of immobility on this test has been used as a measure for behavioral despair, a feature of depression.
  
  
  RESULTS
  The authors found that CX546, compared with dimethyl sulfoxide (DMSO) control, reduced both mechanical and sensory allodynia in SNI (DMSO group, n = 9; CX546 group, n = 11) and CFA models (both DMSO and CX546 groups, n = 9). They found that CX546, compared with control, also reduced depressive symptoms of pain by decreasing immobility on the forced swim test in both SNI (both DMSO and CX546 groups, n = 8) and CFA models (both DMSO and CX546 groups, n = 10). Finally, they found that CX516, compared with control, also reduced mechanical and cold allodynia in the SNI model (both DMSO and CX516 groups, n = 10).
  
  
  CONCLUSIONS
  AMPAkines alleviate pain hypersensitivity as well as depression-like behavior associated with long-lasting nerve injury and inflammatory insult.
authors.affiliation: From the Department of Anesthesiology, New York University School of Medicine, New York, New York (A.M.L., M.L., J.W.); Department of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China (C.S.); and Columbia University, New York, New York (A.Z.).
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Le
authors.forename: Michelle
authors.initials: M
authors.lastname: Lee
authors.forename: Chen
authors.initials: C
authors.lastname: Su
authors.forename: Anthony
authors.initials: A
authors.lastname: Zou
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D004149:Dioxoles / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009437:Neuralgia / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D010880:Piperidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects*; D013550:Swimming / Q000523:psychology
chemical_list: C443080:1-(1,4-benzodioxan-6-ylcarbonyl)piperidine; C097396:1-(quinoxalin-6-ylcarbonyl)piperidine; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000928:Antidepressive Agents; D004149:Dioxoles; D010880:Piperidines; D018091:Receptors, AMPA