Purpose:

Morphine is often used for the treatment of moderate and severe cancer pain, but long-term use can lead to morphine tolerance. Methods for effectively inhibiting morphine tolerance and the related mechanism of action are of great significance for the treatment of cancer pain. Previous studies have shown that electroacupuncture (EA) can inhibit the occurrence of morphine tolerance, but the mechanism is not yet clear. The aim of the present study was to explore the signaling pathway by which EA attenuates the development of bone cancer pain (BCP)-morphine tolerance (MT).

Materials and methods:

Changes in the paw withdrawal threshold (PWT) of rats with bone cancer pain-morphine tolerance were observed in a study of EA combined with intrathecal injection of a PI3K inhibitor (LY294002) or agonist (insulin-like growth factor-1 [IGF-1]). We also tested the protein expression of phosphorylated phosphatidylinositol 3-kinase (p-PI3K), phosphorylated protein kinase B (p-Akt), phosphorylated c-Jun NH₂-terminal kinase 1/2 (p-JNK1/2), and β-arrestin2 in the L4-6 spinal dorsal horn of rats.

Results:

The protein expression of p-PI3K, p-Akt, p-JNK1/2, and β-arrestin2 was upregulated in the L4-6 spinal dorsal horn of rats with bone cancer pain and bone cancer pain-morphine tolerance. EA delayed the occurrence of morphine tolerance in rats with bone cancer pain and downregulated the protein expression of p-PI3K, p-Akt, p-JNK1/2, and β-arrestin2 in the L4-6 spinal dorsal horn of rats with bone cancer pain-morphine tolerance. Intrathecal injection of LY294002 attenuated the development of morphine tolerance and downregulated the protein expression of p-Akt, p-JNK1/2, and β-arrestin2 in the spinal dorsal horn of rats with bone cancer pain-morphine tolerance. In addition, the inhibitory effect of EA on morphine tolerance was reversed by IGF-1.

Conclusion:

The mechanism underlying the ability of EA to attenuate morphine tolerance may be associated with inhibition of the PI3K/Akt/JNK1/2 signaling pathway.

中文翻译：

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电针通过抑制脊髓背角的 PI3K/Akt/JNK1/2 信号通路减弱骨癌痛大鼠的吗啡耐受

目的：

吗啡常用于治疗中重度癌痛，但长期使用可导致吗啡耐受。有效抑制吗啡耐受的方法及相关作用机制对癌痛的治疗具有重要意义。以往的研究表明，电针（EA）可以抑制吗啡耐受的发生，但机制尚不明确。本研究的目的是探索 EA 减弱骨癌痛 (BCP)-吗啡耐受 (MT) 发展的信号通路。

材料和方法：

在EA联合鞘内注射PI3K抑制剂（LY294002）或激动剂（胰岛素样生长因子-1 [IGF-1 ]）。我们还测试了磷酸化磷脂酰肌醇 3-激酶 (p-PI3K)、磷酸化蛋白激酶 B (p-Akt)、磷酸化 c-Jun NH _2-末端激酶 1/2 (p-JNK1/2) 和 β的蛋白质表达-arrestin2 在大鼠 L4-6 脊髓背角。

结果：

p-PI3K、p-Akt、p-JNK1/2和β-arrestin2蛋白表达在骨癌痛和骨癌痛-吗啡耐受大鼠L4-6脊髓背角上调。电针延缓骨癌痛大鼠吗啡耐受的发生，下调骨癌大鼠L4-6脊髓背角p-PI3K、p-Akt、p-JNK1/2和β-arrestin2的蛋白表达疼痛-吗啡耐受。鞘内注射LY294002可减弱吗啡耐受的发展，并下调骨癌痛-吗啡耐受大鼠脊髓背角p-Akt、p-JNK1/2和β-arrestin2的蛋白表达。此外，EA对吗啡耐受的抑制作用被IGF-1逆转。

结论：

EA 减弱吗啡耐受能力的机制可能与抑制 PI3K/Akt/JNK1/2 信号通路有关。