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

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.

Use of micronized palmitoylethanolamide and trans-polydatin in chronic pelvic pain associated with endometriosis. An open-label study

“…Moreover, treatment with Pea-m ® +trans-polydatin, unlike hormonal treatment, improves both quality of life components. these results, in line with experimental results obtained in a model of neuropathic pain (28,29) suggest that Pea behaves not only as symptomatic but as a disease-modifying agent, capable of reducing the nervous tissue alterations responsible for pain.…”

Sodium butyrate and its synthetic amide derivative modulate nociceptive behaviors in mice

“…Despite PPARs are mainly considered lipid sensors, regulating glucose and lipid metabolism in different tissues, their involvement in other physio-pathological conditions has been widely demonstrated [19,32,33]. Zapolska-Downar et al [28] reported a role for NF-kB and PPAR-␣ in the anti-inflammatory effects of butyrate in endothelial cells, as well as in colonocytes.…”

α-Conotoxin RgIA protects against the development of nerve injury-induced chronic pain and prevents both neuronal and glial derangement

“…Paraffin sections of sciatic nerves (14-days post surgery) were analyzed to detect CD86-positive cells, as previously described [15]. L4–L5 DRGs and the L4/L5 segments of the spinal cord, exposed from the lumbovertebral column via laminectomy and identified by tracing the dorsal roots from their respective DRG, were analyzed to assess glial cells.…”