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- Rankin, Linda, 1987-
(författare)
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Chronic pain : from the study of student attitudes and preferences to the in vitro investigation of a novel treatment strategy
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic pain will affect one in five adults during their lifetime, and it exerts a heavy burden on society with major physiological, psychological, social, and economic impacts. The current chronic pain curriculum taught to medical students in most settings is fragmented, inconsistent and inadequate and a vast majority of general practitioners considered their undergraduate training in chronic pain incomplete. Attitudes and beliefs amongst health care personnel are important and have shown to have impact on clinical management. There is currently a knowledge gap that needs to be addressed in this matter. In this thesis, through an online survey, the attitudes and beliefs of medical students in Sweden and Australia were surveyed. Additionally, we explored which factors influence chronic pain management amongst medical students in Sweden and Australia and Swedish general practitioners. We found that Swedish final year students have a more positive attitude towards chronic pain patients compared to Australian students. Both student cohorts perceived chronic pain management education in need of improvement. Furthermore, we found that the relative importance of factors that influence treatment decisions are formed early during undergraduate training, which further underlines the importance of improving pain curricula during undergraduate medical education in order to give the emerging workforce appropriate tools to manage chronic pain.Management of chronic pain urgently requires novel, well-tolerated pharmacological treatment strategies. Palmitoylethanolamide (PEA) is a potential candidate for managing chronic pain. Its analgesic and anti-inflammatory effects have been observed in a range of experimental animal models and clinical trials. However, questions remain as to how PEA exerts its effects and how levels of PEA and its congeners are changed in states of pain and inflammatory disorders in humans. Treatment with PEA decreases cyclooxygenase 2 (COX-2) activity in animal models, but we found that PEA did not have direct effects upon the kinetic properties of COX-2 in a cell free system. However, COX-2 derived eicosanoid levels were reduced by PEA in lipopolysaccharide and interferon-g-stimulated RAW 264.7 cells. With respect to changes in PEA levels in a chronic inflammatory disorder, we investigated PEA levels, in addition to its synthesizing and hydrolysing enzymes in biopsies from patients with oral lichen planus (OLP). We found that the ratio of prostaglandins to PEA was increased in the OLP biopsy samples. Furthermore, PTGS2 mRNA levels (coding for COX-2) were increased in OLP-patients compared to controls relative to NAPEPLD mRNA levels (coding for a key enzyme in the synthesis of PEA). These results suggest that there is a relative deficit of PEA in OLP, raising the possibility that PEA might be useful for the treatment of this disorder.
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| 2. |
- Rankin, Linda, 1987-, et al.
(författare)
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Relative Deficiency of Anti-Inflammatory N-Acylethanolamines Compared to Prostaglandins in Oral Lichen Planus
- 2020
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Ingår i: Biomedicines. - : MDPI. - 2227-9059. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- Oral lichen planus (OLP) is a chronic inflammatory oromucosal disease. The N-acylethanolamines (NAEs), are a family of endogenous biologically active lipid mediators, with palmitoylethanolamide (PEA) being of particular interest here due to its anti-inflammatory and analgesic properties. In this study using oral mucosa biopsies from OLP patients and healthy controls, we investigated whether NAE synthesis was mobilized in response to the inflammation associated with OLP. PTGS2 levels, coding for cyclooxygenase-2 (COX-2), were increased approximately 4-fold in OLP compared to controls and a significant increase in the ratio of PTGS2 to NAPEPLD, the latter coding for a key enzyme in NAE synthesis, was seen. This was matched by an increased ratio of COX-2-derived prostaglandins to PEA in a second patient cohort. We conclude that there is an imbalance between prostaglandins and PEA in OLP, opening up the possibility that PEA might be a useful treatment for this disorder.
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| 3. |
- Rankin, Linda, 1987-, et al.
(författare)
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The Basal Pharmacology of Palmitoylethanolamide
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 21:21
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Forskningsöversikt (refereegranskat)abstract
- Palmitoylethanolamide (PEA, N-hexadecanoylethanolamide) is an endogenous compound belonging to the family of N-acylethanolamines. PEA has anti-inflammatory and analgesic properties and is very well tolerated in humans. In the present article, the basal pharmacology of PEA is reviewed. In terms of its pharmacokinetic properties, most work has been undertaken upon designing formulations for its absorption and upon characterising the enzymes involved in its metabolism, but little is known about its bioavailability, tissue distribution, and excretion pathways. PEA exerts most of its biological effects in the body secondary to the activation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha), but PPAR-alpha-independent pathways involving other receptors (Transient Receptor Potential Vanilloid 1 (TRPV1), GPR55) have also been identified. Given the potential clinical utility of PEA, not least for the treatment of pain where there is a clear need for new well-tolerated drugs, we conclude that the gaps in our knowledge, in particular those relating to the pharmacokinetic properties of the compound, need to be filled.
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