title: Modulating actions of NMDA receptors on pronociceptive effects of locally injected remifentanil in diabetic rats.
abstract: BACKGROUND
  In this study, we investigated the effects of locally (intraplantar) applied remifentanil, a μ opioid receptor agonist, to the paws and tested whether locally N-methyl d-aspartate (NMDA) receptors agonist or antagonist can modify remifentanil-induced effects in diabetic rats.
  
  
  METHODS
  Effects of locally (intraplantar) remifentanil, NMDA and MK801 or their combinations were investigated by measuring the latencies, thresholds and two biochemical parameters (malondialdehyde (MDA) and nitric oxide (NO)), in streptozotocin induced diabetic rats.
  
  
  RESULTS
  Diabetic rats exhibited hyperalgesia and allodynia and remifentanil treatment aggravated the hyperalgesia and allodynia. The hyperalgesic and allodynic effects of remifentanil decreased in diabetic rats as compared to healthy rats. MK801 suppressed the hyperalgesic and allodynic actions of remifentanil in diabetic rats. However, hyperalgesic and allodynic actions of NMDA increased in diabetic rats. In contrast to age matched group, the combination of NMDA and remifentanil did not produce synergistic actions in diabetic rats. The levels of MDA and NO in the paw tissues of the diabetic rats significantly increased. MK801 significantly decreased NO levels, but not MDA, in diabetic rats.
  
  
  CONCLUSIONS
  The hyperalgesic and allodynic actions of locally treated remifentanil may decrease in diabetic conditions. Increases in NMDA receptors activation, reactive oxygen species production and NO release may modify the sensitivity to remifentanil in diabetes induced neuropathic pain states.
authors.affiliation: Department of Biophysics, School of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey. Electronic address: tufanmert@yahoo.com.
authors.forename: Tufan
authors.initials: T
authors.lastname: Mert
authors.affiliation: Anaesthesiology and Reanimation, School of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey.
authors.forename: Hafize
authors.initials: H
authors.lastname: Oksuz
authors.affiliation: Department of Anatomy, School of Medicine, Fatih University, Istanbul, Turkey.
authors.forename: Berin
authors.initials: B
authors.lastname: Tugtag
authors.affiliation: Biochemistry, School of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey.
authors.forename: Metin
authors.initials: M
authors.lastname: Kilinc
authors.affiliation: Anaesthesiology and Reanimation, School of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey.
authors.forename: Nimet
authors.initials: N
authors.lastname: Senoglu
authors.affiliation: Arts and Science Faculty, Department of Chemistry (Biochemistry Division), University of Cukurova, Adana, Turkey.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Bilgin
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D006930:Hyperalgesia / Q000209:etiology; D008315:Malondialdehyde / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists; D000077208:Remifentanil; D013311:Streptozocin / Q000633:toxicity
chemical_list: D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D017450:Receptors, Opioid, mu; D009569:Nitric Oxide; D008315:Malondialdehyde; D013311:Streptozocin; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D000077208:Remifentanil
keywords: Diabetic neuropathy; NMDA; Oxidative stress; Rat; Remifentanil