Pain mechanismPeripheral nerve injury induces cannabinoid receptor 2 protein expression in rat sensory neurons
Section snippets
Animals and surgical methods
Adult male Wistar rats (120–140g; Charles River UK Ltd, Kent, UK), were used in this study. Three animals were used in each group for histochemical analysis. All surgery was performed under enflurane/O2 inhalation anesthesia, according to UK Home Office-approved procedures. All experiments were performed according to Home Office (United Kingdom) guidelines and with approval of the local Novartis Animal Welfare and Ethics committee. The number of animals used and their suffering was minimised.
Results
Anti-CB2 antibody was first tested on cultured control CHO cells and CHO cells expressing CB2 receptor, as well as sections of rat spleen. Fig. 1 shows validation of the CB2 directed antibody by immunolabeling on CB2 expressing (A) but not control CHO cells (B) in culture. Clear staining of CB2 expressing cells is seen in spleen sections as previously described Fig. 1C.
There was no convincing staining in naïve spinal cord or DRG (not shown). However, 14 days following L5 spinal nerve ligation
Discussion
CB2 agonists have been receiving much attention recently as activators of the cannabinoid system that have analgesic effects without the undesirable, centrally mediated, side effects of brain penetrate CB1 ligands. In preclinical studies the CB2 selective agonist HU-308 reduced the paw licking response following formalin injection (Hanus et al., 1999) and the reported CB2 selective agonist AM1241 inhibited both mechanical and thermal hypersensitivity in animals with spinal nerve ligation
Acknowledgments
We would like to thank Natalie Stoakely, Clive Gentry and Sadhana Patel for carrying out the surgeries.
References (46)
- et al.
GAP-43an intrinsic determinant of neuronal development and plasticity
Trends Neurosci
(1997) - et al.
Localisation of cannabinoid receptor 1 in rat dorsal root ganglion using in situ hybridisation and immunohistochemistry
Neuroscience
(2003) - et al.
Differential expression of the CB2 cannabinoid receptor by rodent macrophages and macrophage-like cells in relation to cell activation
Int Immunopharmacol
(2002) - et al.
The effect of site and type of nerve injury on spinal glial activation and neuropathic pain behavior
Exp Neurol
(1999) - et al.
The role of central and peripheral cannabinoid 1 receptors in the antihyperalgesic activity of cannabinoids in a model of neuropathic pain
Pain
(2001) - et al.
Milk intake and survival in newborn cannabinoid CB1 receptor knockout miceevidence for a “CB3” receptor
Eur J Pharmacol
(2003) - et al.
Evidence for the presence of CB2-like cannabinoid receptors on peripheral nerve terminals
Eur J Pharmacol
(1997) Spinal and peripheral mechanisms of cannabinoid antinociceptionbehavioral, neurophysiological and neuroanatomical perspectives
Chem Phys Lipids
(2002)- et al.
Cannabinoid receptors undergo axonal flow in sensory nerves
Neuroscience
(1999) - et al.
Cannabinoidsa real prospect for pain relief?
Curr Opin Pharmacol
(2002)
The biological role of galanin in normal and neuropathic states
Prog Brain Res
CB2 cannabinoid receptor agonistspain relief without psychoactive effects?
Curr Opin Pharmacol
Inhibition of pain responses by activation of CB(2) cannabinoid receptors
Chem Phys Lipids
Novel, not adenylyl cyclase-coupled cannabinoid binding site in cerebellum of mice
Biochem Biophys Res Commun
Evidence for the presence of CB1 cannabinoid receptors on peripheral neurones and for the existence of neuronal non-CB1 cannabinoid receptors
Life Sci
Cannabinoid receptors and pain
Prog Neurobiol
Cannabinoid receptors and their ligands
Prostaglandins Leukot Essent Fatty Acids
The neuronal distribution of cannabinoid receptor type 1 in the trigeminal ganglion of the rat
Neuroscience
Endocannabinoids and painspinal and peripheral analgesia in inflammation and neuropathy
Prostaglandins Leukot Essent Fatty Acids
Actions of cannabinoid receptor ligands on rat cultured sensory neuronesimplications for antinociception
Neuropharmacology
Modulation of transmitter release via presynaptic cannabinoid receptors
Trends Pharmacol Sci
Evidence that CB-1 and CB-2 cannabinoid receptors mediate antinociception in neuropathic pain in the rat
Pain
Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin
J Dermatol Sci
Cited by (212)
Cannabinoids and neuroinflammation: Therapeutic implications
2023, Journal of Affective Disorders ReportsSynthetic cannabinoids reduce the inflammatory activity of microglia and subsequently improve neuronal survival in vitro
2022, Brain, Behavior, and ImmunityUntapped endocannabinoid pharmacological targets: Pipe dream or pipeline?
2021, Pharmacology Biochemistry and Behavior