Acute desensitization of mu opioid receptors is thought to be an initial step in the development of tolerance to opioids. Given the resistance of the respiratory system to develop tolerance, desensitization of neurons in the Kölliker-Fuse (KF), a key area in the respiratory circuit, was examined. The activation of G protein-coupled inwardly rectifying potassium current was measured using whole-...

Acute postoperative pain in patients with opioid tolerance creates a significant management challenge for anesthesiologists and pain medicine physicians. A multimodal approach is key; however other factors can complicate management such as opioid induced hyperalgesia. We present the case of a patient on large amounts of intrathecal opioids for chronic pain syndrome with opioid induced hyperalge...

The tolerance and dependence after chronic medication with morphine are thought to be representative models for studying the plasticity, including the remodeling of neuronal networks. To test the hypothesis that changes in neuronal plasticity observed in opioid tolerance or dependence are derived from increased activity of the anti-opioid nociceptin system, the effects of chronic treatments wit...

BACKGROUND Opioid analgesics are effective in relieving chronic pain, but they have serious adverse effects, including development of tolerance and dependence. Ibudilast, an inhibitor of glial activation and cyclic nucleotide phosphodiesterases, has shown potential in the treatment of neuropathic pain and opioid withdrawal. Because glial cell activation could also be involved in the development...

Long-term use of opioids for pain management results in rapid development of tolerance and dependence leading to severe withdrawal symptoms. We have previously demonstrated that endothelin-A (ETA) receptor antagonists potentiate opioid analgesia and eliminate analgesic tolerance. This study was designed to investigate the involvement of central ET mechanisms in opioid withdrawal. The effect of ...

Previous experiments have shown that mice lacking a functional delta-opioid receptor (DOR-1) gene do not develop analgesic tolerance to morphine. Here we report that mice lacking a functional gene for the endogenous ligand preproenkephalin (ppENK) show a similar tolerance deficit. In addition, we found that the DOR-1 and ppENK knock-outs as well as the NMDA receptor-deficient 129S6 inbred mouse...

Introduction: Morphine is a potent analgesic but its continual use results in analgesic tolerance. Mechanisms of this tolerance remain to be clarified. However, changes in the functions of μ-opioid and N-Methyl-D-aspartate (NMDA) receptors have been proposed in morphine tolerance. We examined changes in gene expression of the NMDA receptor subunit 1 (NR1) at mRNA levels i...

This presentation will review basic and clinical concepts on pain mechanisms underlying opioid analgesia. It describe the structure, function, cellular signaling of receptors; endogenous exogenous receptor ligands; as well central peripheral sites actions. The also discuss novel opioid-based therapeutic strategies, developed from recently gained knowledge structures signaling, patholo...

In the present study, we investigated whether the peripherally acting micro-opioid receptor agonist loperamide would inhibit allodynia in the non-inflamed dermatome of mice with herpetic pain. Subcutaneous (s.c.) injection of loperamide (1 and 3 mg/kg) inhibited allodynia. Local (intraplantar) injection of loperamide (1 and 5 microg/site) also produced an anti-allodynic effect. The peripheral o...

δ-Opioid receptors are G-protein-coupled receptors that regulate nociceptive and emotional responses. It has been well established that distinct agonists acting at the same G-protein-coupled receptor can engage different signaling or regulatory responses. This concept, known as biased agonism, has important biological and therapeutic implications. Ligand-biased responses are well described in c...