Enrico Gugliandolo1, Ramona D'amico1, Marika Cordaro1, Roberta Fusco1, Rosalba Siracusa1, Rosalia Crupi1, Daniela Impellizzeri1, Salvatore Cuzzocrea2,3, Rosanna Di Paola1. 1. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, no 31, 98166, Messina, Italy. 2. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, no 31, 98166, Messina, Italy. salvator@unime.it. 3. Department of Pharmacological and Physiological Science, Saint Louis University, St. Louis, MO, USA. salvator@unime.it.
Abstract
BACKGROUND: Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Inflammation/immune response at the site of nerve lesion is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration; moreover, the damage to peripheral nerve can cause a loss of sensory function and produces a persistent neuropathic pain. N-Acylethanolamines (NAEs) involve a family of lipid molecules existent in animal and plant, of which is N-palmitoylethanolamide (PEA) that arouses great attention owing to its anti-inflammatory, analgesic, and neuroprotective activities. The modulation of specific amidases for NAEs (and in particular NAE-hydrolyzing acid amidase NAAA, which is more selective for PEA) could be a condition to preserve its levels. Here, we investigated, in a mice model of sciatic nerve crush, the effect of 2-pentadecyl-2-oxazoline (PEA-OXA) the oxazoline of PEA that reportedly modulates activity of NAAA. METHODS: In this experimental model, the mice, following the sciatic nerve crush, were treated daily with PEA-OXA at a dose of 10 mg\kg for 14 days. Therefore, we evaluated the effects of PEA-OXA on the degree of injury, on the inhibition of neuropathic pain, and on the inflammatory process, as in the improvement of reparative processes and therefore in the restoration of locomotor function. RESULTS: Our results showed that PEA-OXA (10 mg/kg) treatment, daily, for 14 days after sciatic nerve crush, have an anti-inflammatory and neuroprotective effect and moreover have an analgesic protective effect on hypersensitivity, and improve the functional recovery after nerve crush. CONCLUSIONS: Therefore, treatment with PEA-OXA as a whole has shown a protective effect, which makes it a powerful candidate for the treatment of peripheral nerve injury and neuropathic pain.
<span class="abstract_title">BACKGROUND: Animal models of <span class="Disease">sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Inflammation/immune response at the site of nerve lesion is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration; moreover, the damage to peripheral nerve can cause a loss of sensory function and produces a persistent neuropathic pain. N-Acylethanolamines (NAEs) involve a family of lipid molecules existent in animal and plant, of which is N-palmitoylethanolamide (PEA) that arouses great attention owing to its anti-inflammatory, analgesic, and neuroprotective activities. The modulation of specific amidases for NAEs (and in particular NAE-hydrolyzing acid amidase NAAA, which is more selective for PEA) could be a condition to preserve its levels. Here, we investigated, in a mice model of sciatic nerve crush, the effect of 2-pentadecyl-2-oxazoline (PEA-OXA) the oxazoline of PEA that reportedly modulates activity of NAAA. METHODS: In this experimental model, the mice, following the sciatic nerve crush, were treated daily with PEA-OXA at a dose of 10 mg\kg for 14 days. Therefore, we evaluated the effects of PEA-OXA on the degree of injury, on the inhibition of neuropathic pain, and on the inflammatory process, as in the improvement of reparative processes and therefore in the restoration of locomotor function. RESULTS: Our results showed that PEA-OXA (10 mg/kg) treatment, daily, for 14 days after sciatic nerve crush, have an anti-inflammatory and neuroprotective effect and moreover have an analgesic protective effect on hypersensitivity, and improve the functional recovery after nerve crush. CONCLUSIONS: Therefore, treatment with PEA-OXA as a whole has shown a protective effect, which makes it a powerful candidate for the treatment of peripheral nerve injury and neuropathic pain.
Authors: Pierluigi Tos; Giulia Ronchi; Igor Papalia; Vera Sallen; Josette Legagneux; Stefano Geuna; Maria G Giacobini-Robecchi Journal: Int Rev Neurobiol Date: 2009 Impact factor: 3.230
Authors: Timea Aczél; Angéla Kecskés; József Kun; Kálmán Szenthe; Ferenc Bánáti; Susan Szathmary; Róbert Herczeg; Péter Urbán; Attila Gyenesei; Balázs Gaszner; Zsuzsanna Helyes; Kata Bölcskei Journal: Int J Mol Sci Date: 2020-04-22 Impact factor: 5.923