ReferenceID 3884
Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action
Br J Pharmacol
BACKGROUND AND PURPOSE: Two non-psychoactive cannabinoids, cannabidiol (CBD) and cannabichromene (CBC), are known to modulate in vitro the activity of proteins involved in nociceptive mechanisms, including transient rec
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Record Fields
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- Reference Id
- 3884
- Evidence Id
- 20474
- Core Evidence Id
- 20474
- Source Reference Id
- 1051
- Herb2 Reference Id
- HBREF001778
- Subject Paper Key
- HBIN019550_20942863
- Pubmed Id
- 20942863
- Doi
- 10.1111/j.1476-5381.2010.01063.x
- Paper Title
- Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action
- Paper Abstract
- BACKGROUND AND PURPOSE: Two non-psychoactive cannabinoids, cannabidiol (CBD) and cannabichromene (CBC), are known to modulate in vitro the activity of proteins involved in nociceptive mechanisms, including transient receptor potential (TRP) channels of vanilloid type-1 (TRPV1) and of ankyrin type-1 (TRPA1), the equilibrative nucleoside transporter and proteins facilitating endocannabinoid inactivation. Here we have tested these two cannabinoids on the activity of the descending pathway of antinociception. EXPERIMENTAL APPROACH: Electrical activity of ON and OFF neurons of the rostral ventromedial medulla in anaesthetized rats was recorded extracellularly and tail flick latencies to thermal stimuli were measured. CBD or CBC along with various antagonists were injected into the ventrolateral periaqueductal grey. KEY RESULTS: Cannabidiol and CBC dose-dependently reduced the ongoing activity of ON and OFF neurons in anaesthetized rats, whilst inducing antinociceptive responses in the tail flick-test. These effects were maximal with 3 nmol CBD and 6 nmol CBC, and were antagonized by selective antagonists of cannabinoid CB(1) adenosine A(1) and TRPA1, but not of TRPV1, receptors. Both CBC and CBD also significantly elevated endocannabinoid levels in the ventrolateral periaqueductal grey. A specific agonist at TRPA1 channels and a synthetic inhibitor of endocannabinoid cellular reuptake exerted effects similar to those of CBC and CBD. CONCLUSIONS AND IMPLICATIONS: CBD and CBC stimulated descending pathways of antinociception and caused analgesia by interacting with several target proteins involved in nociceptive control. These compounds might represent useful therapeutic agents with multiple mechanisms of action.
- Journal
- Br J Pharmacol
- Publish Year
- 2011
- Experiment Subject
- rat
- Experiment Type
- Animal Experiment
- Phenotype Related
- Analgesia
- Paper Title Cn
- Paper Title En
- Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action
- Bilingual Status
- semi_complete