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PEA-OXA Mitigates Oxaliplatin-Induced Painful Neuropathy through NF-κB/Nrf-2 Axis

Michela Campolo1, Marika Lanza1, Irene Paterniti1

  • 1Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 98166 Messina, Italy.

International Journal of Molecular Sciences
|April 30, 2021
PubMed

Insights

2-pentadecyl-2-oxazoline (PEA-OXA) effectively reduced oxaliplatin-induced peripheral neuropathy (OIPN) in rats. PEA-OXA mitigated hypersensitivity by modulating glial activation and inflammatory pathways, offering a potential adjunct therapy for chemotherapy-induced chronic pain.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Oncology

Background:

  • Chemotherapy-induced neuropathy is a frequent, dose-dependent adverse effect of antineoplastics like oxaliplatin (L-OHP).
  • Oxaliplatin-induced peripheral neuropathy (OIPN) significantly impacts patients' quality of life, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To evaluate the therapeutic potential of 2-pentadecyl-2-oxazoline (PEA-OXA) in a murine model of oxaliplatin-induced peripheral neuropathy (OIPN).
  • To investigate the underlying molecular mechanisms of PEA-OXA's effects on OIPN, focusing on glial activation, cytokine production, and key signaling pathways.

Main Methods:

  • OIPN was induced in rats using intraperitoneal injections of oxaliplatin (L-OHP).
  • Animals were treated with PEA-OXA or ultramicronized palmitoylethanolamide (PEAum) orally.
  • Neuropathic pain, glial cell activity, cytokine levels, neurotrophic factors, and NF-κB/Nrf-2 pathway activation were assessed.

Main Results:

  • PEA-OXA significantly reduced the development of hypersensitivity in rats compared to PEAum.
  • PEA-OXA treatment decreased glial cell hyperactivation and pro-inflammatory cytokine production in the spinal cord.
  • PEA-OXA upregulated neurotrophic factors in dorsal root ganglia and modulated NF-κB/Nrf-2 signaling pathways.

Conclusions:

  • PEA-OXA demonstrates significant efficacy in ameliorating oxaliplatin-induced peripheral neuropathy in a preclinical model.
  • The therapeutic effects of PEA-OXA are mediated through the modulation of glial activation, inflammation, and the NF-κB/Nrf-2 signaling axis.
  • PEA-OXA presents a promising therapeutic candidate as an adjunct to chemotherapy for managing chronic pain associated with chemotherapy-induced neuropathy.
Keywords:
2-pentadecyl-2-oxazoline (PEA-OXA)dorsal root ganglia (DRG)oxaliplatin (L-OHP)painpalmitoylethanolamide ultramicronized (PEAum)

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