Background

Naloxone has been used as an opioid antagonist to prevent multiple adverse side effects of opioid-like tolerance and hyperalgesia. This study has investigated naloxone combined with morphine to limit pain hypersensitivity. In addition, the expression of brain-derived neurotrophic factor (BDNF) and K⁺ Cl⁻ cotransporter2 (KCC2) were also studied.

Methods

Forty-eight adult male Wistar rats (180–220 g) were divided into eight groups, with six rats in each group. Rats were divided into two tolerance and hyperalgesia groups; the sham group, the morphine group, the treatment group (naloxone along with morphine), and the sham group (naloxone along with saline) for eight consecutive days. Tail-flick test was performed on days 1, 5, and 8, and the plantar test on days 1 and 10. On days 8 and 10, the lumbar segments of the spinal cord were collected, and BDNF and KCC2 expression were analyzed using western blotting and immunohistochemistry, respectively.

Results

Results showed that tolerance and hyperalgesia developed following eight days of repeated morphine injection. BDNF expression significantly increased, but KCC2 was downregulated. Co-administration of naloxone and morphine decreased tolerance and hyperalgesia by decreasing BDNF and increasing KCC2 expression, respectively.

Conclusion

This study suggests that BDNF and KCC2 may be candidate molecules for decreased morphine tolerance and hyperalgesia.

中文翻译：

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纳洛酮可以限制吗啡过敏：考虑分子机制

背景

纳洛酮已被用作阿片类药物拮抗剂，以预防阿片类药物耐受和痛觉过敏的多种不良副作用。本研究研究了纳洛酮与吗啡联合使用以限制疼痛超敏反应。此外，还研究了脑源性神经营养因子（BDNF）和K ⁺ Cl-协同转运蛋白2（KCC2）的表达^。

方法

将 48 只成年雄性 Wistar 大鼠（180-220 g）分为 8 组，每组 6 只。将大鼠分为耐受组和痛觉过敏组；假手术组、吗啡组、治疗组（纳洛酮和吗啡）和假手术组（纳洛酮和盐水）连续八天。第1、5、8天进行甩尾试验，第1、10天进行足底试验。第8、10天，采集脊髓腰段，使用Western blotting分析BDNF和KCC2的表达。分别进行印迹和免疫组织化学。

结果

结果显示，重复注射吗啡八天后出现了耐受性和痛觉过敏。BDNF 表达显着增加，但 KCC2 表达下调。纳洛酮和吗啡联合给药分别通过降低 BDNF 和增加 KCC2 表达来降低耐受性和痛觉过敏。

结论

这项研究表明 BDNF 和 KCC2 可能是吗啡耐受性降低和痛觉过敏的候选分子。