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Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain.
- Source :
-
Pain [Pain] 2019 Jan; Vol. 160 (1), pp. 136-150. - Publication Year :
- 2019
-
Abstract
- 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.
- Subjects :
- Action Potentials drug effects
Animals
Capsaicin analogs & derivatives
Capsaicin pharmacology
Disease Models, Animal
Exploratory Behavior drug effects
Feeding Behavior drug effects
Ganglia, Spinal cytology
Hyperalgesia therapy
Lysergic Acid Diethylamide pharmacology
Male
Maze Learning drug effects
Neuralgia pathology
Piperazines therapeutic use
Piperidines pharmacology
Pyrazoles pharmacology
Pyridines therapeutic use
Rats
Rats, Wistar
Serotonin Antagonists pharmacology
Swimming
Anxiety drug therapy
Anxiety etiology
Cannabidiol therapeutic use
Hyperalgesia drug therapy
Hyperalgesia etiology
Neuralgia complications
Serotonin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-6623
- Volume :
- 160
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Pain
- Publication Type :
- Academic Journal
- Accession number :
- 30157131
- Full Text :
- https://doi.org/10.1097/j.pain.0000000000001386