Relationship between noradrenaline release in the locus coeruleus and antiallodynic efficacy of analgesics in rats with painful diabetic neuropathy

• Published in: Life sciences (1973) 2013-06, Vol.92 (23), p.1138-1144
• Main Authors: Suehiro, Koichi, Funao, Tomoharu, Fujimoto, Yohei, Yamada, Tokuhiro, Mori, Takashi, Nishikawa, Kiyonobu
• Format: Article
• Language: English
• Subjects: Adrenergic Neurons - drug effects; Adrenergic Neurons - physiology; analgesia; Analgesics - pharmacology; Analgesics - therapeutic use; animal models; Animals; Clomipramine - pharmacology; Clomipramine - therapeutic use; correlation; Descending pathway; Diabetes Mellitus, Experimental - complications; Diabetic Neuropathies - drug therapy; Diabetic Neuropathies - physiopathology; Diabetic neuropathy; Female; Hyperalgesia - drug therapy; Hyperalgesia - physiopathology; hypersensitivity; intravenous injection; loci; Locus coeruleus; Locus Coeruleus - chemistry; Locus Coeruleus - drug effects; Locus Coeruleus - physiopathology; microdialysis; morphine; Morphine - pharmacology; Morphine - therapeutic use; naloxone; Naloxone - pharmacology; Noradrenaline; norepinephrine; Norepinephrine - analysis; Norepinephrine - physiology; pain; Rats; Rats, Sprague-Dawley; Tramadol - pharmacology; Tramadol - therapeutic use
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2013.04.015

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). In freely moving rats, basal NA concentrations in LC perfusate were quantitated 72 to 96h 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 20min for 80min. 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. 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.