Ultramicronized Palmitoylethanolamide and Paracetamol, a New Association to Relieve Hyperalgesia and Pain in a Sciatic Nerve Injury Model in Rat.

Abstract

Inflammation is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration; moreover, damage to peripheral nerves can cause a loss of sensory function and produces persistent neuropathic pain. To date, various potential approaches for neuropathic pain have focused on controlling neuroinflammation. The aim of this study was to investigate the neuroprotective effects of a new association of ultramicronized Palmitoylethanolamide (PEAum), an Autacoid Local Injury Antagonist Amide (ALIAmide) with analgesic and anti-inflammatory properties, with Paracetamol, a common analgesic, in a rat model of sciatic nerve injury (SNI). The association of PEAum-Paracetamol, in a low dose (5 mg/kg + 30 mg/kg), was given by oral gavage daily for 14 days after SNI. PEAum-Paracetamol association was able to reduce hyperalgesia, mast cell activation, c-Fos and nerve growth factor (NGF) expression, neural histological damage, cytokine release, and apoptosis. Furthermore, the analgesic action of PEAum-Paracetamol could act in a synergistic manner through the inhibition of the NF-κB pathway, which leads to a decrease of cyclooxygenase 2-dependent prostaglandin E2 (COX-2/PGE2) release. In conclusion, we demonstrated that PEAum associated with Paracetamol was able to relieve pain and neuroinflammation after SNI in a synergistic manner, and this therapeutic approach could be relevant to decrease the demand of analgesic drugs.

• Authors: Alessio Filippo Peritore, Rosalba Siracusa, Roberta Fusco, Enrico Gugliandolo, Ramona D'Amico, Marika Cordaro, Rosalia Crupi, Tiziana Genovese, Daniela Impellizzeri, Salvatore Cuzzocrea, Rosanna Di Paola
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 10 (May 15 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 32429243 (Publication Type: Journal Article)

Chemical References

• Amides
• Cytokines
• Ethanolamines
• Palmitic Acids
• Proto-Oncogene Proteins c-fos
• Acetaminophen
• palmidrol
• Nerve Growth Factor

Topics

• Acetaminophen (pharmacology, therapeutic use)
• Amides (pharmacology, therapeutic use)
• Animals
• Apoptosis (drug effects)
• Astrocytes (drug effects, pathology)
• Cell Degranulation (drug effects)
• Cytokines (metabolism)
• Disease Models, Animal
• Ethanolamines (pharmacology, therapeutic use)
• Hyperalgesia (complications, drug therapy, pathology)
• Inflammation (pathology)
• Mast Cells (drug effects, physiology)
• Microglia (drug effects, pathology)
• Nerve Growth Factor (metabolism)
• Neuralgia (complications, drug therapy, pathology)
• Oxidative Stress (drug effects)
• Palmitic Acids (pharmacology, therapeutic use)
• Proto-Oncogene Proteins c-fos (metabolism)
• Rats
• Sciatic Nerve (drug effects, injuries, pathology)
• Spinal Cord (pathology)