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• W2949680920 abstract "Numerous studies have demonstrated a physiological interaction between the mu opioid receptor (MOR) and delta opioid receptor (DOR) systems. A few studies have shown that dual MOR-DOR agonists could be beneficial, with reduced tolerance and addiction liability, but are nearly untested in chronic pain models, particularly neuropathic pain. In this study, we tested the MOR-DOR agonist SRI-22141 in mice in the clinically relevant models of HIV Neuropathy and Chemotherapy-Induced Peripheral Neuropathy (CIPN). SRI-22141 was more potent than morphine in the tail flick pain test and had equal or enhanced efficacy versus morphine in both neuropathic pain models, with significantly reduced tolerance. SRI-22141 also produced no jumping behavior during naloxone-precipitated withdrawal in CIPN or naïve mice, suggesting that SRI-22141 produces little to no dependence. SRI-22141 also reduced tumor necrosis factor-α and cyclooxygenase-2 in CIPN in the spinal cord, suggesting an anti-inflammatory mechanism of action. The DOR-selective antagonist naltrindole strongly reduced CIPN efficacy and anti-inflammatory activity in the spinal cord, without affecting tail flick antinociception, suggesting the importance of DOR activity in these models. Overall, these results provide compelling evidence that MOR-DOR agonists could have strong efficacy with reduced side effects and an anti-inflammatory mechanism in the treatment of neuropathic pain. Perspective This study demonstrates that a MOR-DOR dual agonist given chronically in chronic neuropathic pain models has enhanced efficacy with strongly reduced tolerance and dependence, with a further anti-inflammatory effect in the spinal cord. This suggests that MOR-DOR dual agonists could be effective treatments for neuropathic pain with reduced side effects." @default.
• W2949680920 created "2019-06-27" @default.
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• W2949680920 date "2020-01-01" @default.
• W2949680920 modified "2023-10-14" @default.
• W2949680920 title "A Novel Mu-Delta Opioid Agonist Demonstrates Enhanced Efficacy With Reduced Tolerance and Dependence in Mouse Neuropathic Pain Models" @default.
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• W2949680920 doi "https://doi.org/10.1016/j.jpain.2019.05.017" @default.
• W2949680920 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6906261" @default.
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