Abstract：
AIMS: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). MAIN 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. KEY FINDINGS: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. SIGNIFICANCE: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.
journal_name
Life Scijournal_title
Life sciencesauthors
Suehiro K,Funao T,Fujimoto Y,Yamada T,Mori T,Nishikawa Kdoi
10.1016/j.lfs.2013.04.015subject
Has Abstractpub_date
2013-06-21 00:00:00pages
1138-44issue
23eissn
0024-3205issn
1879-0631pii
S0024-3205(13)00240-3journal_volume
92pub_type
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