Benefits of Camelina sativa Supplementation in Morphine Treatment: Enhanced Analgesia, Delayed Tolerance and Reduced Gut Side Effects Through PPAR-α Receptor Engagement

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2519 - 2519

Опубликована: Март 11, 2025

Long-term opioid therapies are severely limited by the development of analgesic tolerance and gastrointestinal side effects. Camelina sativa, a plant Brassicaceae family, modulates activity peroxisome proliferator-activated receptor α (PPAR-α receptor), which is involved in regulation pain processing gut physiology. The aim this study was to evaluate efficacy sativa defatted seed meal (DSM) supplementation on effects after repeated treatment with morphine naïve mice. Co-administering DSM (1 g kg−1 p.o.) (10 mg s.c.) increased duration opioid-induced acute effect. also delayed onset same result obtained through either simultaneously administering camelina or 24 h before injection for entire experiment. counteracted intestinal damage visceral hypersensitivity caused treatment. beneficial morphine-related were prevented via pre-treatment PPAR-α antagonist GW6471, though latter did not influence tolerance. In conclusion, could be used as supplement improve therapeutic profile morphine.

Язык: Английский

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Fixed combination of palmitoylethanolamide and melatonin in preventive therapy of migraine: results from a randomized clinical trial

Frontiers in Nutrition, Год журнала: 2025, Номер 12

Опубликована: Апрель 10, 2025

Migraines are neurological disorders which significantly impact quality of life. Current pharmacological treatments often have adverse effects, prompting the search for alternatives with fewer side effects. Several studies described antimigraine properties palmitoylethanolamide (PEA) and melatonin. Our research assessed efficacy association hydrodispersible PEA (1,200 mg) melatonin (0.2 by a randomized, three-month, double-blind, placebo-controlled trial (PEATONIDE®; n = 30 patients; placebo; patients). The participants were recruited "I.N.B.B. Consortium" in Italy. primary outcome was reduction migraine frequency, while secondary outcomes included intensity, duration, grade disability. parameters self-reported daily headache diary. formulation displayed significant frequency (T3 months: 2.2 ± 0.4 MMDs; T0 baseline: 3.4 0.5 MMDs, ***p < 0.001 vs baseline T0) disability, incidence associated symptoms attacks after 3 months treatment. No effects observed during In addition, mitigation migraine-related symptomatology observed. These findings suggest that PEATONIDE® may be promising adjunctive approach management. However, given relatively small sample size, further large-scale multicenter trials needed to confirm its clinical applicability broader population.

Язык: Английский

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Immune Dysregulation in Depression and Anxiety: A Review of the Immune Response in Disease and Treatment

Cells, Год журнала: 2025, Номер 14(8), С. 607 - 607

Опубликована: Апрель 17, 2025

Rates of depression and anxiety have increased significantly in recent decades, with many patients experiencing treatment-resistant symptoms. Beyond psychiatric manifestations, these conditions are associated heightened risks suicide, cardiovascular disease, chronic pain, fatigue. Emerging research suggests that neuroinflammation, immune dysregulation, hypothalamic–pituitary–adrenal axis dysfunction contribute to their pathophysiology, often interacting bidirectionally stress. While current first-line treatments primarily target neurotransmitter imbalances, do not achieve symptom resolution, highlighting the need for novel approaches. This review explores role dysfunction, cytokine activity, interactions anxiety. Additionally, we examine how existing pharmacological non-pharmacological interventions influence inflammation responses. Understanding mechanisms may pave way more integrative treatment strategies combine modulation traditional therapies.

Язык: Английский

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

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(10), С. 2787 - 2787

Опубликована: Май 9, 2024

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

Язык: Английский

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

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 9079 - 9079

Опубликована: Авг. 21, 2024

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

Язык: Английский

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

Nutrients, Год журнала: 2024, Номер 17(1), С. 121 - 121

Опубликована: Дек. 30, 2024

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

Язык: Английский

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