Ultramicronized N-palmitoylethanolamine associated with analgesics: Effects against persistent pain

Nobili, Stefania; Micheli, Laura; Lucarini, Elena; Toti, Alessandra; Ghelardini, Carla; Di Cesare Mannelli, Lorenzo

doi:10.1016/j.pharmthera.2024.108649

Cited by 3 publications

(1 citation statement)

References 213 publications

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“…The pain-relieving effect of PEA in its micronized (mPEA) and ultramicronized (um-PEA) forms (which increase its bioavailability and biological efficacy) [27,28] was demonstrated in patients suffering from chronic pain of different origins, such as radiculopathy, osteoarthritis, postherpetic neuralgia, diabetic neuropathy, and pain associated with oncologic disease, suggesting an independence between umPEA's effects and pain pathogenesis [29][30][31][32][33][34]. Importantly, it was also reported that m/umPEA, in addition to the lack of both acute and chronic toxicity, is well tolerated and has no interactions with other concomitant pharmacological therapies [16,35].…”

Section: Introductionmentioning

confidence: 99%

Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain Related to Chronic Inflammatory Demyelinating Polyneuropathy: A Proof-of-Concept Study

Cocito,

Peci,

Torrieri

et al. 2024

JCM

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Background/Objectives: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune disease. Neuropathic pain (NP), related to peripheral inflammation, is among its earliest manifestations. This preliminary open-label investigation aimed to evaluate the efficacy of ultramicronized Palmitoylethanolamide (umPEA) in the management of NP. Methods: A total of 14 patients with CIDP, already undergoing immunoglobulin (Ig) therapy, were divided into two groups: Group A received umPEA 600 mg twice daily in addition to Ig for 60 days, followed by Ig alone until the end of the observation (180 days); Group B received Ig alone for 120 days and subsequently umPEA + Ig in the last 60 days of the study. Painful symptom intensity and quality of life were assessed by the Numeric Rating Scale, Neuropathic Pain Symptoms Inventory, and Five Dimensions Health Questionnaire. The safety umPEA profile was evaluated. Results: UmPEA in addition to immunoglobulins allowed for a significant improvement over time in all NP symptoms intensity (p = 0.0007) and in patients’ quality of life (p = 0.0036). Conclusions: This study suggests umPEA as a safe and effective treatment in addition to immunoglobulins to improve NP, ameliorating the patient’s health status. These results highlight the importance of neuroinflammation modulation in the management of CIDP’s painful symptoms, drawing attention to umPEA’s potential use also in neuropathies of different etiologies.

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Section: Introductionmentioning

confidence: 99%

Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain Related to Chronic Inflammatory Demyelinating Polyneuropathy: A Proof-of-Concept Study

Cocito,

Peci,

Torrieri

et al. 2024

JCM

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Palmitoylethanolamide as a Supplement: The Importance of Dose-Dependent Effects for Improving Nervous Tissue Health in an In Vitro Model

Galla,

Mulè,

Ferrari

et al. 2024

IJMS

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Palmitoylethanolamide (PEA) is a highly lipophilic molecule with low solubility, making absorption difficult. Recent techniques like micronisation, ultra-micronisation and combining PEA with solvents have improved their bioavailability and stability. Our study analysed particle size differences and absorption kinetics using specific solvents (PEAΩ and PEA DynoΩ) over time (0.5 h–6 h) in a dose-dependent manner (200 mg–1800 mg). The results showed that PEAΩ and PEA DynoΩ achieved 82–63% absorption at 3 h, compared to 30–60% for micronised, ultra-micronised PEA and a commercial product, highlighting the optimal dose range of 300 mg–600 mg. In addition, a 3D model of the peripheral nerve was utilised to explain the efficacy after gut passage and support the most effective dose (300 mg or 600 mg) achieved at the gut level. PEAΩ and PEA DynoΩ, which are associated with better intestinal bioavailability compared to PEA-micronised, PEA ultra-micronised and a commercial product, have allowed not only a reduction in the inflammatory context but also an improvement of peripheral nerve well-being by increasing specific markers like MPZ (26–36% vs. 8–15%), p75 (25–32% vs. 13–16%) and NRG1 (22–29.5% vs. 11–14%). These results highlight the potential of advanced PEA formulations to overcome solubility challenges and maintain in vitro efficacy, modulating peripheral nerve well-being.

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The Unripe Carob Extract (Ceratonia siliqua L.) as a Potential Therapeutic Strategy to Fight Oxaliplatin-Induced Neuropathy

Micheli,

Muraglia,

Corbo

et al. 2024

Nutrients

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Background: Oxaliplatin-induced neuropathy (OIN) is a severe painful condition that strongly affects the patient’s quality of life and cannot be counteracted by the available drugs or adjuvants. Thus, several efforts are devoted to discovering substances that can revert or reduce OIN, including natural compounds. The carob tree, Ceratonia siliqua L., possesses several beneficial properties. However, its antalgic properties have not been substantially investigated and only a few investigations have been conducted on the unripe carob (up-CS) pods. Thus, the aims of this study were to evaluate for the first time the unripe variety of Apulian carob, chemically characterized and profiled as antioxidant potential of polyphenolic compounds as well as to investigate the ability of up-CS to reduce the neurotoxicity in a mouse model of oxaliplatin-induced neuropathic pain. Methods: By UHPLC-HRMS/MS analyses, 50 phenolic compounds, belonging mainly to n-galloylated glucoses and flavonoids were detected. Results: In a mouse model of oxaliplatin-induced neurotoxicity (2.4 mg/kg, 10 injections over two weeks), acute per os treatment with up-CS provoked a dose-dependent pain-relieving effect that completely counteracted oxaliplatin hypersensitivity at the dose of 200 mg/kg. Repeated oral administration of up-CS (100 mg/kg), concomitantly with oxaliplatin injection, exerted a protective effect against the development of thermal and mechanical allodynia. In addition, up-CS exerted a neuroprotective role against oxaliplatin-induced astrocytes activation in the spinal cord measured as GFAP-fluorescence intensity. Conclusions: Overall, our study contributes to the knowledge on up-CS properties by highlighting its protective activity in the painful condition related to the administration of oxaliplatin.

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Ultramicronized N-palmitoylethanolamine associated with analgesics: Effects against persistent pain

Cited by 3 publications

References 213 publications

Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain Related to Chronic Inflammatory Demyelinating Polyneuropathy: A Proof-of-Concept Study

Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain Related to Chronic Inflammatory Demyelinating Polyneuropathy: A Proof-of-Concept Study

Palmitoylethanolamide as a Supplement: The Importance of Dose-Dependent Effects for Improving Nervous Tissue Health in an In Vitro Model

The Unripe Carob Extract (Ceratonia siliqua L.) as a Potential Therapeutic Strategy to Fight Oxaliplatin-Induced Neuropathy

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