title: Relationship between noradrenaline release in the locus coeruleus and antiallodynic efficacy of analgesics in rats with painful diabetic neuropathy.
abstract: OBJECTIVE
  In animal models of neuropathic pain, the noradrenergic descending pain inhibitory pathways from the locus coeruleus (LC) may be suppressed. However, no study has investigated the correlation between noradrenaline (NA) release in the LC and efficacy of analgesics in rats with painful diabetic neuropathy. Using microdialysis and analysis of mechanical hypersensitivity, we investigated the correlation between NA release in the LC and efficacy of morphine, tramadol, and clomipramine in rats with diabetic mellitus (DM).
  
  
  METHODS
  In freely moving rats, basal NA concentrations in LC perfusate were quantitated 72 to 96 h after microdialysis probe implantation. Following intravenous administration of each drug, NA concentrations were expressed as a percentage of basal values. We concurrently measured the threshold to elicit a paw withdrawal response every 20 min for 80 min.
  
  
  RESULTS
  NA concentrations in the LC perfusate were significantly higher in the tramadol and clomipramine groups compared to the morphine group. Naloxone administration did not significantly affect NA concentrations. In the morphine group, NA release in the LC was not significantly correlated with the pain threshold. In contrast, in the tramadol and clomipramine groups, NA release in the LC was significantly correlated with the pain threshold. The correlation coefficient was higher in the clomipramine group than in the tramadol group.
  
  
  CONCLUSIONS
  Our results suggest that the descending noradrenergic pathway can play an important role in analgesia for DM neuropathy and that there is a significant correlation between NA release in the LC and the efficacy of tramadol and clomipramine.
authors: Department of Anesthesiology, Osaka City University Graduate School of Medicine, 1-5-7 Asahimachi, Abenoku, Osaka City, Osaka 545-8586, Japan.
authors: Koichi
authors: K
authors: Suehiro
authors: Tomoharu
authors: T
authors: Funao
authors: Yohei
authors: Y
authors: Fujimoto
authors: Tokuhiro
authors: T
authors: Yamada
authors: Takashi
authors: T
authors: Mori
authors: Kiyonobu
authors: K
authors: Nishikawa
mesh_terms: D059331:Adrenergic Neurons / Q000187:drug effects / Q000502:physiology; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002997:Clomipramine / Q000494:pharmacology / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology; D008125:Locus Coeruleus / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology*; D009020:Morphine / Q000494:pharmacology / Q000627:therapeutic use; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000032:analysis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014147:Tramadol / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D009270:Naloxone; D014147:Tramadol; D009020:Morphine; D002997:Clomipramine; D009638:Norepinephrine