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Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain
- Publication Year :
- 2019
- Publisher :
- NLM (Medline), 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 :
- Male
Anxiety
Cannabidiol
Dorsal raphe
Electrophysiology
Pain
Pyridines
Action Potentials
Pharmacology
Piperazines
chemistry.chemical_compound
0302 clinical medicine
Piperidines
030202 anesthesiology
Ganglia, Spinal
Allodynia
Neurology
Hyperalgesia
Neuropathic pain
Serotonin Antagonists
medicine.symptom
Capsazepine
medicine.drug
Elevated plus maze
Serotonin
medicine.drug_class
TRPV1
Anxiolytic
03 medical and health sciences
medicine
Animals
Rats, Wistar
Maze Learning
Swimming
business.industry
Antagonist
Feeding Behavior
Rats
Disease Models, Animal
Lysergic Acid Diethylamide
Anesthesiology and Pain Medicine
chemistry
Exploratory Behavior
Neuralgia
Pyrazoles
Neurology (clinical)
Capsaicin
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....d112071a9763b0a1d18dd4d09f23cfc2