Calignano, A

D'Agostino, G

Di Cesare Mannelli, L

Ghelardini, C

Pacini, A

Russo, R

Zanardelli, M

Mediators of Inflammation

English

PubMed

Aberdeen University Research

Palmitoylethanolamide is a disease-modifying agent in peripheral neuropathy : pain relief and neuroprotection share a PPAR-alpha-mediated mechanism

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

D'Agostino, G.

Pacini, A.

Russo, R.

Zanardelli, M.

Ghelardini, C.

Calignano, A.

The University of Manchester - Institutional Repository

Palmitoylethanolamide Is a Disease-ModifyingAagent in Peripheral Neuropathy:Pain Relief and Neuroprotection Share a PPAR-Alpha-Mediated Mechanism

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

L. Di Cesare Mannelli

G. D'Agostino

A. Pacini

R. Russo

M. Zanardelli

C. Ghelardini

A. Calignano

Directory of Open Access Journals

Palmitoylethanolamide Is a Disease-Modifying Agent in Peripheral Neuropathy: Pain Relief and Neuroprotection Share a PPAR-Alpha-Mediated Mechanism

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−1PEA 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-αnull 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.</jats:p

Crossref

Di Cesare Mannelli, Lorenzo

Pacini, Alessandra

Zanardelli, Matteo

Ghelardini, Carla

Florence Research

Palmitoylthanolamide is a disease-modifying agent in peripheral neuropathy: pain relief and neuroprotection share a PPAR-apha-mediated mechanism.

https://aura.abdn.ac.uk/bitstream/2164/5666/1/328797.pdf

Palmitoylethanolamide is a disease-modifying agent in peripheral neuropathy : pain relief and neuroprotection share a PPAR-alpha-mediated mechanism

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Aberdeen University Research

The University of Manchester - Institutional Repository

Directory of Open Access Journals

Crossref

The University of Manchester - Institutional Repository

Florence Research

The University of Manchester - Institutional Repository