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 a...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/328797 |
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| author | L. Di Cesare Mannelli G. D'Agostino A. Pacini R. Russo M. Zanardelli C. Ghelardini A. Calignano |
| author_facet | L. Di Cesare Mannelli G. D'Agostino A. Pacini R. Russo M. Zanardelli C. Ghelardini A. Calignano |
| author_sort | L. Di Cesare Mannelli |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-bde42e4ce8b3499a8b4fc1f610235202 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-bde42e4ce8b3499a8b4fc1f6102352022025-02-03T05:48:26ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/328797328797Palmitoylethanolamide Is a Disease-Modifying Agent in Peripheral Neuropathy: Pain Relief and Neuroprotection Share a PPAR-Alpha-Mediated MechanismL. Di Cesare Mannelli0G. D'Agostino1A. Pacini2R. Russo3M. Zanardelli4C. Ghelardini5A. Calignano6Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence, ItalyDepartment of Experimental Pharmacology, University of Naples Federico II, 80131 Naples, ItalyDepartment of Anatomy, Histology and Forensic Medicine, University of Florence, 50139 Florence, ItalyDepartment of Experimental Pharmacology, University of Naples Federico II, 80131 Naples, ItalyDepartment of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence, ItalyDepartment of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence, ItalyDepartment of Experimental Pharmacology, University of Naples Federico II, 80131 Naples, ItalyNeuropathic 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.http://dx.doi.org/10.1155/2013/328797 |
| spellingShingle | L. Di Cesare Mannelli G. D'Agostino A. Pacini R. Russo M. Zanardelli C. Ghelardini A. Calignano Palmitoylethanolamide Is a Disease-Modifying Agent in Peripheral Neuropathy: Pain Relief and Neuroprotection Share a PPAR-Alpha-Mediated Mechanism Mediators of Inflammation |
| title | Palmitoylethanolamide Is a Disease-Modifying Agent in Peripheral Neuropathy: Pain Relief and Neuroprotection Share a PPAR-Alpha-Mediated Mechanism |
| title_full | Palmitoylethanolamide Is a Disease-Modifying Agent in Peripheral Neuropathy: Pain Relief and Neuroprotection Share a PPAR-Alpha-Mediated Mechanism |
| title_fullStr | Palmitoylethanolamide Is a Disease-Modifying Agent in Peripheral Neuropathy: Pain Relief and Neuroprotection Share a PPAR-Alpha-Mediated Mechanism |
| title_full_unstemmed | Palmitoylethanolamide Is a Disease-Modifying Agent in Peripheral Neuropathy: Pain Relief and Neuroprotection Share a PPAR-Alpha-Mediated Mechanism |
| title_short | Palmitoylethanolamide Is a Disease-Modifying Agent in Peripheral Neuropathy: Pain Relief and Neuroprotection Share a PPAR-Alpha-Mediated Mechanism |
| title_sort | palmitoylethanolamide is a disease modifying agent in peripheral neuropathy pain relief and neuroprotection share a ppar alpha mediated mechanism |
| url | http://dx.doi.org/10.1155/2013/328797 |
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