Cancer-related bone pain is attenuated by a systemically available δ-opioid receptor agonist

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• 作者：Josue Brainin-Mattos ; Nicole D. Smith ; Shelle Malkmus ; Yosup Rew ; Murray Goodman ; Joseph Taulane and Tony L. Yaksh
• 关键词：Osteosarcoma ; Morphine ; Allodynia
• 刊名：Pain
• 出版年：2006
• 出版时间：May 2006
• 年：2006
• 卷：122
• 期：1-2
• 页码：174-181
• 全文大小：197 K

文摘

Patients with bone cancer report severe pain and receive μ-opioids. We developed a family of peptidomimetic δ-agonists, one of which H₂N-Tyr-dVal-Gly-Phe-Ala-OH binds with a 1700× affinity at the δ versus μ receptor. To examine the systemic analgesic efficacy of this δ-agonist versus morphine in osteosarcoma pain, osteosarcoma cells are injected into one femur of the anesthetized mouse. After 10–18 days, a decalcification of the injected femur occurs along with a pronounced tactile allodynia. IP morphine and produced a dose-dependent reversal of allodynia with the respective ED₅₀ values being 5.3 ± 1.9 mg/kg for morphine and 1.3 ± 0.3 mg/kg for [. Plotting peak effect versus area under the analgesic curve for doses of morphine and [ revealed overlapping curves suggesting that for a given effect, [ produced a similar duration of action as morphine. These effects were reversed by IP naloxone (3 mg/kg). IP naltrindole (1 mg/kg) preferentially reversed [. The upper dose effects of morphine but not [ were limited by pronounced hyperactivity. No other effects were noted. These results show that IP [ through a δ receptor produces analgesia equal in efficacy to that of morphine but with a 4.5-fold greater potency. Over the doses examined, morphine actions were side effect limited. The δ side effects were not so limited, suggesting a favorable therapeutic ratio for δ-agonists in this pain model. These studies suggest that a systemically delivered δ-opioid agonist has pronounced analgesic properties on a preclinical cancer pain model.