title: Epidural tezampanel, an AMPA/kainate receptor antagonist, produces postoperative analgesia in rats.
abstract: BACKGROUND
  We evaluated the epidural administration of tezampanel, a non-N-methyl-d-aspartate receptor antagonist, in a rat model for postoperative pain. We sought to determine if this drug affects nociception when administered epidurally by testing its effects on responses to heat in normal rats. The effects of epidural tezampanel on pain-related behaviors in rats that underwent plantar incision were also studied.
  
  
  METHODS
  Rats were anesthetized and epidural catheters were placed. One day after epidural catheterization, the baseline heat withdrawal latency was measured. Epidural tezampanel or morphine was tested for analgesia by examining their effects against heat withdrawal latency. Motor function was also tested. Comparisons to subcutaneous drug administration were made. Other rats underwent plantar incision after epidural catheterization to assess pain behavior caused by incision. The effects of epidural tezampanel on the cumulative pain scoring, based on guarding, the withdrawal threshold to von Frey filament application, and the withdrawal latency to heat, were measured. The effects of epidural tezampanel on arterial blood pressure and heart rate were also tested.
  
  
  RESULTS
  Both epidural morphine and epidural tezampanel increased withdrawal latency to heat. Only subcutaneous morphine affected heat withdrawal latency. After plantar incision, epidural tezampanel decreased the median guarding pain score, increased the heat withdrawal latency and increased the mechanical withdrawal threshold indicating analgesic effects. Arterial blood pressure and heart rate did not change after epidural drug administration.
  
  
  CONCLUSIONS
  These experiments demonstrate that epidural administration of tezampanel produces analgesia to heat, motor side effects in some rats, and reduces pain behaviors caused by incision. No systemic analgesia was apparent using the largest dose.
authors: Department of Anesthesia, University of Iowa College of Medicine, Iowa City, IA 52242-1079, USA. tim-brennan@uiowa.edu
authors: Hee Cheol
authors: HC
authors: Jin
authors: Amber J
authors: AJ
authors: Keller
authors: Jong Kwon
authors: JK
authors: Jung
authors: Alberto
authors: A
authors: Subieta
authors: Timothy J
authors: TJ
authors: Brennan
mesh_terms: D015360:Analgesia, Epidural; D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D001522:Behavior, Animal; D006358:Hot Temperature; D007279:Injections, Subcutaneous; D007546:Isoquinolines / Q000008:administration & dosage*; D008297:Male; D009020:Morphine / Q000008:administration & dosage; D010147:Pain Measurement; D017288:Pain Threshold; D010149:Postoperative Pain / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors*; D013777:Tetrazoles / Q000008:administration & dosage*; D016138:Walking
chemical_list: D000701:Analgesics, Opioid; D007546:Isoquinolines; D009020:Morphine; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D013777:Tetrazoles; C082309:tezampanel