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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 well‐demonstrated 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 μ‐, κ‐ or δ‐opioid receptor agonists, nonsteroidal analgesics, α_2C‐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 …