Cannabidiol reduces lipopolysaccharide‐induced nociception via endocannabinoid system activation

Abstract

Bacterial infections are often accompanied by fever and generalized muscle pain. However, the treatment of pain with an infectious aetiology has been overlooked. Thus, we investigated the impact of cannabidiol (CBD) in bacterial lipopolysaccharide (LPS)-induced nociception. Male Swiss mice received intrathecal (i.t.) LPS injection, and the nociceptive threshold was measured by the von Frey filaments test. Spinal involvement of the cannabinoid CB 2 receptor, toll-like receptor 4 (TLR4), microglia and astrocytes were evaluated by i.t. administration of their respectively antagonists or inhibitors. Western blot, immunofluorescence, ELISA and liquid chromatography-mass spectrometry were used to assess Cannabinoid CB 2 receptors and TLR4 spinal expression, proinflammatory cytokines and endocannabinoid levels. CBD was administered intraperitoneally at 10 mg/kg. The pharmacological assay demonstrated TLR4 participation in LPS-induced nociception. In addition, spinal TLR4 expression and proinflammatory cytokine levels were increased in this process. CBD treatment prevented LPS-induced nociception and TLR4 expression. AM630 reversed antinociception and reduced CBD-induced endocannabinoids up-regulation. Increased spinal expression of the cannabinoid CB 2 receptor was also found in animals receiving LPS, which was accompanied by reduced TLR4 expression in CBD-treated mice. Taken together, our findings indicated that CBD is a potential treatment strategy to control LPS-induced pain by attenuating TLR4 activation via the endocannabinoid system.

Cannabis and Endometriosis: The Roles of the Gut Microbiota and the Endocannabinoid System

“…Cannabinoid receptor 1 CB 1 G-protein coupled receptor found on cells in the central and peripheral nervous system-involved in processes of mood, appetite, learning, memory and pain [45] Cannabinoid receptor 2 CB 2 G-protein coupled receptor found on cells in the central and peripheral nervous system-expressed during active inflammation [45] Anandamide AEA Agonist towards CB N-oleoylethanolamine OEA Fatty acid ethanolamine-involved in food intake, inflammation and pain [45] N-palmitoylethanolamine PEA Low affinity for CB 1 , CB 2 and TRPV1-induces peripheral antinociception upon activating CB 1 and CB 2 [45] Fatty acid amide hydrolase FAAH Metabolises endogenous ligands [45] Monoglyceride lipase MGL Metabolises endogenous ligands [45] Research to date has demonstrated that the ECS is involved in homeostasis and regulation via neuromodulatory activity, physiological processes such as digestion [46], immune function [47], nociception [48], appetite regulation [49], cardiovascular and respiratory function [50] and sleep-wake cycles [51].…”

Editorial: Chronic Inflammation and Related Diseases: From Mechanisms to Therapies

“…Cannabidiol (CBD), isolated from the plant extract of Cannabis sativa , which has a long history of medicinal use, is a well-known compound with reported analgesic and anti-inflammatory effects in various animal models of neuropathic pain, inflammatory pain, and arthritis. CBD inhibits lipopolysaccharide (LPS)-induced nociception by suppressing the expression of Toll-like receptor 4 (TLR4) through the in vivo cannabinoid system [ 14 ]. Further, the combination of CBD and tetrahydrocannabivarin lead to a more substantial improvement in the pain behavioral response compared to single administration in chemotherapy-induced neuropathic pain.…”