Palmitoylethanolamide is a disease-modifying agent in peripheral neuropathy

pain relief and neuroprotection share a PPAR-alpha-mediated mechanism

L Di Cesare Mannelli, G D'Agostino, A Pacini, R Russo, M Zanardelli, C Ghelardini, A Calignano

Research output: Contribution to journalArticle

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Abstract

Neuropathic syndromes which are evoked by lesions to the peripheral or central nervous system are extremely difficult to treat, and available drugs rarely joint an antihyperalgesic with a neurorestorative effect. N-Palmitoylethanolamine (PEA) exerts antinociceptive effects in several animal models and inhibits peripheral inflammation in rodents. Aimed to evaluate the antineuropathic properties of PEA, a damage of the sciatic nerve was induced in mice by chronic constriction injury (CCI) and a subcutaneous daily treatment with 30 mg kg(-1) PEA was performed. On the day 14, PEA prevented pain threshold alterations. Histological studies highlighted that CCI induced oedema and an important infiltrate of CD86 positive cells in the sciatic nerve. Moreover, osmicated preparations revealed a decrease in axon diameter and myelin thickness. Repeated treatments with PEA reduced the presence of oedema and macrophage infiltrate, and a significant higher myelin sheath, axonal diameter, and a number of fibers were observable. In PPAR- α null mice PEA treatment failed to induce pain relief as well as to rescue the peripheral nerve from inflammation and structural derangement. These results strongly suggest that PEA, via a PPAR- α -mediated mechanism, can directly intervene in the nervous tissue alterations responsible for pain, starting to prevent macrophage infiltration.
Original languageEnglish
Article number328797
Number of pages12
JournalMediators of Inflammation
Volume2013
DOIs
Publication statusPublished - 2013

Fingerprint

PPAR alpha
Peripheral Nervous System Diseases
Pain
Peroxisome Proliferator-Activated Receptors
Sciatic Nerve
Myelin Sheath
Constriction
Edema
Macrophages
Inflammation
Nerve Tissue
Pain Threshold
Peripheral Nervous System
Wounds and Injuries
palmidrol
Neuroprotection
Peripheral Nerves
Axons
Rodentia
Therapeutics

Keywords

  • animals
  • blotting, western
  • endocannabinoids
  • ethanolamines
  • hyperalgesia
  • immunohistochemistry
  • male
  • mice
  • mice, knockout
  • PPAR alpha
  • palmitic acids
  • peripheral nervous system diseases

Cite this

Di Cesare Mannelli, L., D'Agostino, G., Pacini, A., Russo, R., Zanardelli, M., Ghelardini, C., & Calignano, A. (2013). Palmitoylethanolamide is a disease-modifying agent in peripheral neuropathy: pain relief and neuroprotection share a PPAR-alpha-mediated mechanism. Mediators of Inflammation, 2013, [328797]. https://doi.org/10.1155/2013/328797

Palmitoylethanolamide is a disease-modifying agent in peripheral neuropathy : pain relief and neuroprotection share a PPAR-alpha-mediated mechanism. / Di Cesare Mannelli, L; D'Agostino, G; Pacini, A; Russo, R; Zanardelli, M; Ghelardini, C; Calignano, A.

In: Mediators of Inflammation, Vol. 2013, 328797, 2013.

Research output: Contribution to journalArticle

Di Cesare Mannelli, L ; D'Agostino, G ; Pacini, A ; Russo, R ; Zanardelli, M ; Ghelardini, C ; Calignano, A. / Palmitoylethanolamide is a disease-modifying agent in peripheral neuropathy : pain relief and neuroprotection share a PPAR-alpha-mediated mechanism. In: Mediators of Inflammation. 2013 ; Vol. 2013.
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