title: Effects of glycemic regulation on chronic postischemia pain.
abstract: BACKGROUND
  Ischemia-reperfusion (I/R) injuries consist of enhanced oxidative and inflammatory responses along with microvascular dysfunction after prolonged ischemia and reperfusion. Because I/R injuries induce chronic postischemia pain (CPIP) in laboratory animals, it is possible that surgical procedures using prolonged ischemia may result in chronic postoperative pain. Glycemic modulation during ischemia and reperfusion could affect pain after I/R injury because glucose triggers oxidative, inflammatory, and thrombotic reactions, whereas insulin has antioxidative, antiinflammatory, and vasodilatory properties.
  
  
  METHODS
  One hundred ten rats underwent a 3-h period of ischemia followed by reperfusion to produce CPIP. Rats with CPIP had previously been divided into six groups with differing glycemic modulation paradigms: normal feeding; fasting; fasting with normal saline administration; fasting with dextrose administration; normal feeding with insulin administration; and normal feeding with insulin and dextrose administration. Blood glucose concentration was assessed during I/R in these separate groups of rats, and these rats were tested for mechanical and cold allodynia over the 21 days afterward (on days 2, 5, 7, 9, 12, and 21 after I/R injury).
  
  
  RESULTS
  I/R injury in rats with normoglycemia or relative hyperglycemia (normal feeding and fasting with dextrose administration groups) led to significant mechanical and cold allodynia; conversely, relative hypoglycemia associated with insulin treatment or fasting (fasting, fasting with normal saline administration, and normal feeding with insulin administration groups) reduced allodynia induced by I/R injury. Importantly, insulin treatment did not reduce allodynia when administered to fed rats given dextrose (normal feeding with dextrose and insulin administration group).
  
  
  CONCLUSIONS
  Study results suggest that glucose levels at the time of I/R injury significantly modulate postinjury pain thresholds in rats with CPIP. Strict glycemic control during I/R injury significantly reduces CPIP and, conversely, hyperglycemia significantly enhances it, which could have potential clinical applications especially in the surgical field.
authors.affiliation: Department of Anesthesia, Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Ross-Huot
authors.forename: André
authors.initials: A
authors.lastname: Laferrière
authors.forename: Cho Min
authors.initials: CM
authors.lastname: Gi
authors.forename: Mina
authors.initials: M
authors.lastname: Khorashadi
authors.forename: Thomas
authors.initials: T
authors.lastname: Schricker
authors.forename: Terence J
authors.initials: TJ
authors.lastname: Coderre
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002908:Chronic Disease; D003080:Cold Temperature; D005215:Fasting / Q000502:physiology; D005528:Foot / Q000098:blood supply / Q000473:pathology; D007839:Functional Laterality / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006358:Hot Temperature; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy* / Q000209:etiology*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D010147:Pain Measurement; D010812:Physical Stimulation; D051381:Rats; D020318:Rats, Long-Evans; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000150:complications*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose