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Involvement of the L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in peripheral antinociception induced by N-palmitoyl-ethanolamine in rats
- Source :
- Journal of Neuroscience Research. 90:1474-1479
- Publication Year :
- 2012
- Publisher :
- Wiley, 2012.
-
Abstract
- N-palmitoyl-ethanolamine (PEA) is an endogenous substance that was first identified in lipid tissue extracts. It has been classified as a CB2 receptor agonist. Exogenous PEA has the potential to become a valid treatment for neuropathic and inflammatory pain. In spite of the welldemonstrated antiinflammatory properties of PEA, its involvement in controlling pain pathways remains poorly characterized. The participation of the L-arginine/nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway in peripheral antinociception has been established by our group to the l-, j -o rd-opioid receptor agonists, nonsteroidal analgesics, a2C-adrenoceptor agonists, and even nonpharmacological electroacupuncture. The aim of this study was to verify whether the peripheral antinociception effects of PEA involve the activation of this pathway. All drugs were locally administered to the right hind paw of male Wistar rats. The paw pressure test was used, with hyperalgesia induced by intraplantar injection of prostaglandin E2. PEA elicited a local peripheral antinociceptive effect that was antagonized by the nonselective NO synthase (NOS) inhibitor L-NOARG and the selective neuronal NOS (nNOS) inhibitor L-NPA. Selective inhibition of endothelial (eNOS) and inducible (iNOS) NOS via L-NIO and L-NIL, respectively, was ineffective at blocking the effects of a local PEA injection. In addition, the dosage of nitrite in the homogenized paw, as determined by colorimetric assay, indicated that exogenous PEA is able to induce NO release. The soluble guanylyl cyclase inhibitor ODQ antagonized the PEA effect, whereas the cGMP-phosphodiesterase inhibitor zaprinast potentiated the antinociceptive effect of low-dose PEA. This study provides evidence that PEA activates nNOS, thus initiating the NO/cGMP pathway and inducing peripheral antinociceptive effects. V C 2012 Wiley Periodicals, Inc.
- Subjects :
- Male
Nociception
Agonist
medicine.drug_class
Palmitic Acids
Pharmacology
Arginine
Nitric Oxide
Nitric oxide
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Neural Pathways
Randall–Selitto test
medicine
Cannabinoid receptor type 2
Animals
Rats, Wistar
Cyclic GMP
Cyclic guanosine monophosphate
Analgesics
food and beverages
Neural Inhibition
Amides
Rats
Disease Models, Animal
chemistry
Biochemistry
Ethanolamines
Hyperalgesia
medicine.symptom
Zaprinast
Soluble guanylyl cyclase
Endocannabinoids
Subjects
Details
- ISSN :
- 03604012
- Volume :
- 90
- Database :
- OpenAIRE
- Journal :
- Journal of Neuroscience Research
- Accession number :
- edsair.doi.dedup.....6b1dd30811f8d2c331adea4782288adb