Abstract |
Most of the modulating effects of cannabinoids on pain are through putative cannabinoid CB1 and CB2 receptors. However, the involvement of other receptors is also suggested. Cannabinoid compounds with analgesic activity such as palmitoylethanolamide (PEA) show low affinity to CB1 and CB2 receptors, yet selectively activate GPR55 receptors. The objective of the present study was to evaluate the possible role of spinal CB1 and GPR55 receptors on antinociceptive activity of PEA in formalin test as well as in the spinal expression of IL1-β in rat. Intrathecal (i.t.) administration of PEA (1, 10 μg) significantly decreased both pain-related scores in formalin test and IL1-β expression in rat spinal cord. Pretreatment of rats with low doses of CB1 receptor antagonist/GPR55 receptor agonist AM251 (10, 100 ng; i.t.), did not attenuated the effect of PEA, yet even significantly increased the effect of PEA on IL1-β expression in rat spinal cord. Interestingly, i.t. administration of low doses of AM251 per se significantly decreased both pain related behavior and spinal IL1-β expression in formalin test. These findings suggest the possible involvement of receptors other than CB1 receptors in spinal pain pathways, such as GPR55, in pain modulating activity of cannabinoids.
|
Authors | Nima Naderi, Mohsen Majidi, Zahra Mousavi, Solaleh Khoramian Tusi, Zahra Mansouri, Fariba Khodagholi |
Journal | Neurochemical research
(Neurochem Res)
Vol. 37
Issue 4
Pg. 778-85
(Apr 2012)
ISSN: 1573-6903 [Electronic] United States |
PMID | 22201038
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Amides
- Endocannabinoids
- Ethanolamines
- GPR55 protein, rat
- Interleukin-1beta
- Palmitic Acids
- Piperidines
- Pyrazoles
- Receptor, Cannabinoid, CB1
- Receptors, Cannabinoid
- Receptors, G-Protein-Coupled
- AM 251
- palmidrol
|
Topics |
- Amides
- Animals
- Drug Interactions
(physiology)
- Endocannabinoids
(administration & dosage, metabolism)
- Ethanolamines
(administration & dosage, metabolism)
- Injections, Spinal
- Interleukin-1beta
(biosynthesis)
- Male
- Pain
(drug therapy, metabolism)
- Pain Measurement
(drug effects)
- Palmitic Acids
(administration & dosage, metabolism)
- Piperidines
(administration & dosage, metabolism)
- Pyrazoles
(administration & dosage, metabolism)
- Rats
- Rats, Wistar
- Receptor, Cannabinoid, CB1
(antagonists & inhibitors, metabolism)
- Receptors, Cannabinoid
(metabolism)
- Receptors, G-Protein-Coupled
(agonists, metabolism)
- Spinal Cord
(drug effects, metabolism)
|