Exploring the therapeutic potential of cannabidiol for sleep deprivation-induced hyperalgesia
Copyright © 2024 Elsevier Ltd. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:249 |
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| Enthalten in: |
Neuropharmacology - 249(2024) vom: 15. März, Seite 109893 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhu, Kangsheng [VerfasserIn] |
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| Links: |
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| Themen: |
19GBJ60SN5 |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 25.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.neuropharm.2024.109893 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369183584 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cannabinoids | |
| 650 | 4 | |a Nucleus accumbens | |
| 650 | 4 | |a Pain | |
| 650 | 4 | |a Sleep deprivation | |
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| 700 | 1 | |a Qin, Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Wanjun |e verfasserin |4 aut | |
| 700 | 1 | |a Hao, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Xiaolei |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Han |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Zuxiao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Sheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Zongmao |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Tengfei |e verfasserin |4 aut | |
| 700 | 1 | |a Kong, Dezhi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wei |e verfasserin |4 aut | |
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