title: Insulin implants prevent the temporal development of mechanical allodynia and opioid hyposensitivity for 24-wks in streptozotocin (STZ)-diabetic Wistar rats.
abstract: OBJECTIVE
  As the diabetes control and complications trial showed that intensive glycemic control in patients with Type 1 diabetes decreased the risk of development of long-term microvascular complications including painful diabetic neuropathy by approximately 60%, hyperglycemia was implicated as a causal factor in the etiology of this condition. Hence, the present study was designed as a 24-week longitudinal investigation of the extent to which the level of glycemic control in the streptozotocin (STZ)-diabetic rat model of Type 1 diabetes affects the development of mechanical allodynia and opioid hyposensitivity in these animals.
  
  
  RESULTS
  Diabetes was fully developed (blood glucose levels ≥ 15 mM) in adult male Wistar rats by 7 days after intravenous STZ (75 mg/kg) administration. Mechanical allodynia developed in a temporal manner in the rat hindpaws, such that it was fully developed by 6 weeks and persisted for at least 24 weeks post-STZ administration. Morphine hyposensitivity also developed in a temporal manner in the same animals. By contrast, restoration and maintenance of euglycemia using insulin implants commencing at diabetes diagnosis on Day 7 post-streptozotocin administration, prevented development of both mechanical allodynia and opioid hyposensitivity in STZ-diabetic rats for the 24-week study duration.
  
  
  CONCLUSIONS
  This study shows that long-term restoration of euglycemia over a 6-month period in STZ-diabetic rats prevents the hallmark symptoms of PDN including morphine hyposensitivity.
  
  
  CONCLUSIONS
  Our findings are consistent with epidemiological data showing that tight glycemic control in patients with Type 1 diabetes markedly reduces the prevalence of PDN, further implicating persistent hyperglycemia as a pathogenic factor.
authors.affiliation: The University of Queensland, School of Pharmacy, St. Lucia Campus, Brisbane, Queensland, Australia.
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Otto
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Wyse
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cabot
authors.forename: Maree T
authors.initials: MT
authors.lastname: Smith
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D004361:Drug Tolerance; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000517:prevention & control; D020007:Implants, Experimental; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use*; D008297:Male; D009020:Morphine / Q000627:therapeutic use; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000701:Analgesics, Opioid; D001786:Blood Glucose; D007328:Insulin; D009020:Morphine