• Mohammed Shaqura, Baled I Khalefa, Mehdi Shakibaei, Christian Zöllner, Mahmoud Al-Khrasani, Susanna Fürst, Michael Schäfer, and Shaaban A Mousa.
• Department of Anaesthesiology and Intensive Care Medicine, Charité University Berlin, Campus Virchow Klinikum and Campus Charite Mitte, Augustenburgerplatz 1, 13353 Berlin, Germany.
• Neuropharmacology. 2014 Oct 1; 85: 142-50.

AbstractPainful diabetic neuropathy is a disease of the peripheral sensory neuron with impaired opioid responsiveness. Since μ-opioid receptor (MOR) activation can inhibit the transient receptor potential vanilloid 1 (TRPV1) activity in peripherally sensory neurons, this study investigated the mechanisms of impaired opioid inhibitory effects on capsaicin-induced TRPV1 activity in painful diabetic neuropathy. Intravenous injection of streptozotocin (STZ, 45 mg/kg) in Wistar rats led to a degeneration of insulin producing pancreatic β-cells, elevated blood glucose, and mechanical hypersensitivity (allodynia). In these animals, local morphine's inhibitory effects on capsaicin-induced nocifensive behavior as well as on capsaicin-induced TRPV1 current in dorsal root ganglion cells were significantly impaired. These changes were associated with a loss in MOR but not TRPV1 in peripheral sensory neurons. Intrathecal delivery of nerve growth factor in diabetic animals normalized sensory neuron MOR and subsequently rescued morphine's inhibitory effects on capsaicin-induced TRPV1 activity in vivo and in vitro. These findings identify a loss in functional MOR on sensory neurons as a contributing factor for the impaired opioid inhibitory effects on capsaicin-induced TRPV1 activity during advanced STZ-induced diabetes. Moreover, they support growing evidence of a distinct regulation of opioid responsiveness during various painful states of disease (e.g. arthritis, cancer, neuropathy) and may give novel therapeutic incentives. Copyright © 2014 Elsevier Ltd. All rights reserved.

36 keywords...

hide…