Pea
Sahar Swidan, Matthew Bennett in Advanced Therapeutics in Pain Medicine, 2020
Many of the receptors, channels, and cytokines that PEA interacts with are involved in inflammatory pain signaling (e.g., PPAR-α), immune systems (e.g., GPR55), and endocrine systems (e.g., GPR119). As discussed by Skaper et al.,1 inflammation is a protective response in the human body that is initiated during the cellular healing process. However, when inflammation is prolonged it can cause damage and lead to pain, neurologic diseases, and other inflammatory disorders. Palmitoylethanolamide accomplishes its anti-inflammatory and anti-nociceptive effects by binding to and modulating PPAR-α, which is a regulator of the gene networks controlling pain and inflammation. This gene network switches NF-κB off, which is involved in the pathology of peripheral neuropathies, carpal tunnel syndrome, sciatic pain, osteoarthritis, low-back pain, dental pain, multiple sclerosis, chronic pelvic pain, postherpetic neuralgia, and vaginal pain.5 The cannabinoid-like receptors GPR55 and GPR119 have been linked to inflammation in the gut related to immune system modulation and GLP-1 secretion from entero-endocrine cells, respectively.6 Additionally, PEA influences potassium channels involved in pain perception and desensitizes the TRPV1 channel on sensory neurons. These pharmacodynamic relationships are what gives PEA its anti-inflammatory, immune-modulatory, and anti-nociceptive properties.
Peripheral Neuropathy
Charles Theisler in Adjuvant Medical Care, 2023
Palmitoylethanolamide (PEA): Many patients suffering from neuropathic conditions have pain that is refractory to existing treatments. In this context, palmitoylethanolamide (PEA), an endogenous fatty acid amide, is emerging as a novel agent in the treatment of pain and inflammation.16 Palmitoylethanolamide is available as a supplement (PeaPure and PeaPlex) and as a cream (PEA cream).
Herpes simplex virus type 1 and Alzheimer’s disease: link and potential impact on treatment
Published in Expert Review of Anti-infective Therapy, 2019
Roberta Mancuso, Mariaconcetta Sicurella, Simone Agostini, Peggy Marconi, Mario Clerici
Other natural products with an antiviral action and the ability of inducing protection from neurodegeneration are Resveratrol (RSV) and Quercetin, which are known activators of Sirt1 (NAD+-dependent deacetylase sirtuin 1) and AMPK (5ʹAMP-activated protein kinase) [154–157]. Several studies have demonstrated that, during neuronal infection, HSV-1 modulates the AMPK/Sirt1 axis. Particularly, AMPK is down-regulated during early infection; on the other hand, the levels of Sirt1 increase, suggesting that the AMPK/Sirt1 axis is differentially modulated by the virus during infection [158]. RSV and Quercetin activate the AMPK/Sirt1 axis and induce neuroprotective and antiviral effects in HSV-1-infected neuronal cultures [159]. Other studies have demonstrated the capacity of RSV and Quercetin to delay axonal degeneration after injury [158], to block accumulation of Aβ peptide in vitro [159], to reduce BACE-1, which mediates the APP cleavage [158], and to provide protection from brain ischemia in both adult and neonatal rodents [160,161]. Palmitoylethanolamide (PEA), an endogenous lipid mediator is also endowed with anti-inflammatory and neuroprotective effects [162]. A murine model showed that PEA counteracted the activation and inflammation seen in AD-like mouse astrocytes and promoted neuronal viability [163]. Table 3 summarizes the drugs discussed in this paragraph.
Recent developments in interferon-based therapies for multiple sclerosis
Published in Expert Opinion on Biological Therapy, 2018
Laura Dumitrescu, Cris S. Constantinescu, Radu Tanasescu
All classical IFN-β formulations show good long-term safety profiles but have frequent tolerability and adherence issues, mainly related to injection-site reactions, and dose-related flu-like syndrome [66]. The former there are seen in up to 90% of the patients receiving subcutaneous formulations, and in about a third of those using the intramuscular route [90]. Reactions are usually mild and do not require IFN-β cessation. The flu-like syndrome includes fever, chills, fatigue, myalgia, and headache, beginning 4–6 h after IFN-β administration, and persisting for up to 24 h [41]. During the first months of treatment, these symptoms may affect up to ~75% of the patients, but subsequently their incidence decreases [91]. Some patients also experience dose-related transient worsening of MS symptoms, typically resolving 3 months after treatment initiation [41]. Strategies to mitigate these side effects include gradual titration to full-dose schedules, optimal scheduling of IFN-β administration, and the use of acetaminophen or non-steroidal anti-inflammatory drugs [90]. A recent placebo-controlled trial showed that adding oral ultramicronized palmitoylethanolamide (600 mg/day), an endogenous bioactive lipid, to subcutaneous IFN-β-1a, may reduce injection-related pain and increase the perceived cognitive performance and health status of RRMS patients [92]. A small randomized, placebo-controlled, cross-over trial that found no benefit in reducing flu-like symptoms from adding cetirizine (a second-generation histamine 1 antagonist) to the standard IFN-β-1b treatment [91].
Nutritional intervention in chronic pain: an innovative way of targeting central nervous system sensitization?
Published in Expert Opinion on Therapeutic Targets, 2020
Jo Nijs, Sevilay Tumkaya Yilmaz, Ömer Elma, Joe Tatta, Patrick Mullie, Luc Vanderweeën, Peter Clarys, Tom Deliens, Iris Coppieters, Nathalie Weltens, Lukas Van Oudenhove, Eva Huysmans, Anneleen Malfliet
Another potential therapeutic way of targeting neuroinflammation in chronic pain relates to the mast-cell glial axis in neuroinflammation. Activated mast cells may contribute to glial activation through its release of an array of mediators after degranulation, including pro-inflammatory cytokines (IL-1β, TNF-α) and nerve growth factor [80]. Mast cells and microglia interact in a bidirectional fashion, including through Toll-like receptor isoforms-2 and −4, mast-cell tryptase, and proteinase-activated receptor 2 on microglia [80]. The naturally occurring fatty acid N-palmitoylethanolamine (or palmitoylethanolamide) is an endogenous molecule abundant in the mammalian brain with established anti-inflammatory and analgesic properties, potentially through inhibiting mast-cell activation [80]. This way, they hold potential as innovative therapeutic target for chronic postsurgical and nonsurgical pain.
Related Knowledge Centers
- Anandamide
- Endocannabinoid System
- Fatty Acid Amide
- Peroxisome Proliferator-Activated Receptor Alpha
- Gpr55
- Gpr119
- Cannabinoid Receptor 1
- Cannabinoid Receptor 2
- N-Acylethanolamine
- Entourage Effect