Hyperalgesia resulting from sleep deprivation (SD) poses a significant a global public health challenge with limited treatment options. The nucleus accumbens (NAc) plays a crucial role in the modulation of pain and sleep, with its activity regulated by two distinct types of medium spiny neurons (MSNs) expressing dopamine 1 or dopamine 2 (D1-or D2) receptors (referred to as D1-MSNs and D2-MSNs, respectively). However, the specific involvement of the NAc in SD-induced hyperalgesia remains uncertain. Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has demonstrated analgesic effects in clinical and preclinical studies. Nevertheless, its potency in addressing this particular issue remains to be determined. Here, we report that SD induced a pronounced pronociceptive effect attributed to the heightened intrinsic excitability of D2-MSNs within the NAc in Male C57BL/6N mice. CBD (30 mg/kg, i.p.) exhibited an anti-hyperalgesic effect. CBD significantly improved the thresholds for thermal and mechanical pain and increased wakefulness by reducing delta power. Additionally, CBD inhibited the intrinsic excitability of D2-MSNs both and . Bilateral microinjection of the selective D2 receptor antagonist raclopride into the NAc partially reversed the antinociceptive effect of CBD. Thus, these findings strongly suggested that SD activates NAc D2-MSNs, contributing heightened to pain sensitivity. CBD exhibits antinociceptive effects by activating D2R, thereby inhibiting the excitability of D2-MSNs and promoting wakefulness under SD conditions.

中文翻译：

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探索大麻二酚对睡眠剥夺引起的痛觉过敏的治疗潜力

睡眠剥夺（SD）引起的痛觉过敏对全球公共卫生构成了重大挑战，但治疗选择有限。伏隔核 (NAc) 在疼痛和睡眠的调节中起着至关重要的作用，其活动由表达多巴胺 1 或多巴胺 2（D1 或 D2）受体（称为分别为 D1-MSN 和 D2-MSN）。然而，NAc 在 SD 诱导的痛觉过敏中的具体参与仍不确定。大麻二酚 (CBD) 是一种非精神活性植物大麻素，在临床和临床前研究中已证明具有镇痛作用。然而，其解决这一特定问题的效力仍有待确定。在这里，我们报告说，SD 诱导了明显的伤害感受效应，归因于雄性 C57BL/6N 小鼠 NAc 内 D2-MSN 的内在兴奋性增强。 CBD（30 mg/kg，腹腔注射）表现出抗痛觉过敏作用。 CBD 通过降低 Delta 功率，显着提高了热痛和机械痛的阈值，并提高了清醒度。此外，CBD 抑制 D2-MSN 的内在兴奋性。将选择性 D2 受体拮抗剂雷氯必利双侧显微注射到 NAc 中部分逆转了 CBD 的镇痛作用。因此，这些发现强烈表明 SD 激活 NAc D2-MSN，有助于提高疼痛敏感性。 CBD 通过激活 D2R 表现出抗伤害作用，从而抑制 D2-MSN 的兴奋性并促进 SD 条件下的清醒。