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

International Journal of Molecular Sciences, 2020 · DOI: 10.3390/ijms21103509 · Published: May 15, 2020

Simple Explanation

This study investigates the neuroprotective effects of combining ultramicronized Palmitoylethanolamide (PEAum) with Paracetamol in rats with sciatic nerve injury (SNI). PEAum is an Autacoid Local Injury Antagonist Amide (ALIAmide) with analgesic and anti-inflammatory properties. The study found that a low dose combination of PEAum and Paracetamol, given orally, reduced hyperalgesia, mast cell activation, and neural histological damage in the rats after SNI. The analgesic action of PEAum and Paracetamol may work together by inhibiting the NF-κB pathway, leading to a decrease in cyclooxygenase 2-dependent prostaglandin E2 (COX-2/PGE2) release.

Study Duration

14 days

Participants

Sprague–Dawley rats (males 270–300 g)

Evidence Level

Not specified

Key Findings

1
PEAum–Paracetamol association reduced hyperalgesia, mast cell activation, c-Fos and nerve growth factor (NGF) expression, neural histological damage, cytokine release, and apoptosis in a rat model of sciatic nerve injury (SNI).
2
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.
3
PEAum associated with Paracetamol was able to relieve pain and neuroinflammation after SNI in a synergistic manner.

Research Summary

The study demonstrated that the association of PEAum and Paracetamol, in a low dose (5 mg/kg + 30 mg/kg), reduced hyperalgesia, mast cell activation, c-Fos and nerve growth factor (NGF) expression, neural histological damage, cytokine release, and apoptosis. 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. The therapeutic strategy with the use of lower doses than those commonly used of PEAum and Paracetamol could be important to combat several diseases associated to pain and inflammation.

Practical Implications

Reduced Analgesic Demand

The synergistic effect of PEAum and Paracetamol could reduce the demand for higher doses of analgesic drugs.

Novel Therapeutic Approach

The combination of PEAum and Paracetamol represents a potential new therapeutic approach for managing neuropathic pain.

Potential for Broad Application

This therapeutic strategy could be important to combat several diseases associated to pain and inflammation.

Study Limitations

1
Further studies are needed to better understand the targets of this pharmacological synergy.
2
The study was conducted on rats, and the results may not directly translate to humans.
3
Not specified

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