Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain.
Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain.
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DOI：
10.1097/j.pain.0000000000001386
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发表时间：
2019-01
期刊：
影响因子：
7.4
通讯作者：
Gobbi G
中科院分区：
文献类型：
--
作者：
De Gregorio D;McLaughlin RJ;Posa L;Ochoa-Sanchez R;Enns J;Lopez-Canul M;Aboud M;Maione S;Comai S;Gobbi G
小剂量大麻二醇可改善神经病理性疼痛模型大鼠的机械性痛觉异常和焦虑行为，并恢复受损的5-羟色胺能传递。临床研究表明，大麻二酚(CBD)是大麻中主要的非成瘾成分，与5-羟色胺(5-羟色胺)1A受体相互作用，可能具有镇痛和缓解焦虑的作用。然而，它对5-羟色胺神经元活动的影响以及它对神经病理性疼痛模型的影响尚不清楚。首先，利用大鼠在体单单位细胞外记录，我们证明了急性静脉注射(i.v.)增加CBD0.11.0 mg/kg可降低中缝背核5-羟色胺能神经元的放电频率，此作用可被静脉注射5-HT1a拮抗剂Way 100635(0.3 mg/kg)所阻断。TRPV1拮抗剂卡萨西平(1 mg/kg，静脉注射)但不能被CB1受体拮抗剂AM 251(1 mg/kg静脉注射)所抑制。CBD(5 mg/kg/d，皮下注射，连续7d)通过脱敏5-HT1a受体，增加5-羟色胺的释放。采用备用神经损伤模型24天的大鼠，在高架迷宫实验、旷场实验和新奇抑制摄食实验中，5-羟色胺的放电活性降低，机械痛觉异常，焦虑样行为增加。CBD治疗7天可减少机械性痛觉异常，减少焦虑样行为，并使5-羟色胺活性正常化。卡萨西平(10 mg/kg/d，皮下注射，连续7天)可完全阻断卡萨西平的抗过敏作用，途径100635(2 mg/kg/d，皮下注射，共7天)可部分阻断卡萨西平的抗过敏作用，而其抗焦虑作用仅被阻断。总体而言，小剂量CBD的重复治疗主要通过激活TRPV1来诱导镇痛，通过激活5-HT1a受体来减少焦虑，并在神经病理性疼痛条件下拯救受损的5-HT神经传递。
Low dose of cannabidiol ameliorates mechanical allodynia and anxious behavior and restores impaired serotonergic transmission in a neuropathic pain model in rats. Clinical studies indicate that cannabidiol (CBD), the primary nonaddictive component of cannabis that interacts with the serotonin (5-HT)1A receptor, may possess analgesic and anxiolytic effects. However, its effects on 5-HT neuronal activity, as well as its impact on models of neuropathic pain are unknown. First, using in vivo single-unit extracellular recordings in rats, we demonstrated that acute intravenous (i.v.) increasing doses of CBD (0.1-1.0 mg/kg) decreased the firing rate of 5-HT neurons in the dorsal raphe nucleus, which was prevented by administration of the 5-HT1A antagonist WAY 100635 (0.3 mg/kg, i.v.) and the TRPV1 antagonist capsazepine (1 mg/kg, i.v.) but not by the CB1 receptor antagonist AM 251 (1 mg/kg, i.v.). Repeated treatment with CBD (5 mg/kg/day, subcutaneously [s.c.], for 7 days) increased 5-HT firing through desensitization of 5-HT1A receptors. Rats subjected to the spared nerve injury model for 24 days showed decreased 5-HT firing activity, mechanical allodynia, and increased anxiety-like behavior in the elevated plus maze test, open-field test, and novelty-suppressed feeding test. Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity. Antiallodynic effects of CBD were fully prevented by capsazepine (10 mg/kg/day, s.c., for 7 days) and partially prevented by WAY 100635 (2 mg/kg/day, s.c., for 7 days), whereas the anxiolytic effect was blocked only by WAY. Overall, repeated treatment with low-dose CBD induces analgesia predominantly through TRPV1 activation, reduces anxiety through 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.
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影响因子：
7.6
作者：
Bambico, Francis Rodriguez;Cassano, Tommaso;Gobbi, Gabriella
通讯作者：
Gobbi, Gabriella
影响因子：
7.4
作者：
Bardin, L;Lavarenne, J;Eschalier, A
通讯作者：
Eschalier, A
影响因子：
4.8
作者：
Campos, Alline Cristina;Ferreira, Frederico Rogerio;Guimaraes, Francisco Silveira
通讯作者：
Guimaraes, Francisco Silveira
影响因子：
2.5
作者：
Chen, Jun;Song, Yang;Su, Hai-chuan
通讯作者：
Su, Hai-chuan
DOI：
10.3181/00379727-71-17123
发表时间：
1949-01-01
影响因子：
--
作者：
BERLIN, NI;HUFF, RL;HENNESSY, TG
通讯作者：
HENNESSY, TG