Exploring the therapeutic potential of cannabidiol for sleep deprivation-induced hyperalgesia.

Abstract

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 in vitro and in vivo. 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.

• Authors: Kangsheng Zhu, Siruan Chen, Xia Qin, Wanjun Bai, Jie Hao, Xiaolei Xu, Han Guo, Hui Bai, Zuxiao Yang, Sheng Wang, Zongmao Zhao, Tengfei Ji, Dezhi Kong, Wei Zhang
• Journal: Neuropharmacology (Neuropharmacology) Vol. 249 Pg. 109893 (May 15 2024) ISSN: 1873-7064 [Electronic] England
• PMID: 38428482 (Publication Type: Journal Article)
• Copyright: Copyright © 2024 Elsevier Ltd. All rights reserved.

Chemical References

• Cannabidiol
• Dopamine
• Receptors, Dopamine D2
• Receptors, Dopamine D1
• Analgesics

Topics

• Mice
• Animals
• Male
• Cannabidiol (pharmacology, therapeutic use)
• Hyperalgesia (drug therapy, etiology)
• Sleep Deprivation (complications, drug therapy)
• Dopamine (pharmacology)
• Mice, Inbred C57BL
• Receptors, Dopamine D2 (metabolism)
• Nucleus Accumbens
• Pain
• Receptors, Dopamine D1 (metabolism)
• Analgesics (pharmacology, therapeutic use)
• Mice, Transgenic