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Rankin, L., Lindkvist, M., Backman, A. C., Sköldunger, A., Lövheim, H., Edvardsson, D. & Gustafsson, M. (2024). Pharmacological treatment of pain in Swedish nursing homes: prevalence and associations with cognitive impairment and depressive mood. Scandinavian Journal of Pain, 24(1), Article ID 20240007.
Open this publication in new window or tab >>Pharmacological treatment of pain in Swedish nursing homes: prevalence and associations with cognitive impairment and depressive mood
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2024 (English)In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 24, no 1, article id 20240007Article in journal (Refereed) Published
Abstract [en]

Objectives: Chronic pain is highly prevalent in nursing home residents and often occurs with depression as well as cognitive impairment, which can severely influence and limit the expression of pain.

Methods: The present cross-sectional study aimed to estimate the prevalence of pain, depressive mood, and cognitive impairment in association with pharmacological treatment against pain and depressive symptoms among Swedish nursing home residents.

Results: We found an overall pain prevalence of 52.8%, a prevalence of 63.1% for being in a depressive mood, and a prevalence of cognitive impairment of 68.3%. Among individuals assessed to have depressive mood, 60.5% were also assessed to have pain. The prevalence of pharmacological treatment for pain was 77.5 and 54.1% for antidepressants. Prescription of pharmacological treatment against pain was associated with reports of currently having pain, and paracetamol was the most prescribed drug. A higher cognitive function was associated with more filled prescriptions of drugs for neuropathic pain, paracetamol, and nonsteroidal anti-inflammatory drugs (NSAIDs), which could indicate an undertreatment of pain in those cognitively impaired.

Conclusion: It is important to further explore the relationship between pain, depressive mood, and cognitive impairment in regard to pain management in nursing home residents.

Place, publisher, year, edition, pages
Walter de Gruyter, 2024
Keywords
cross-sectional studies, depression, elderly, pain, pain management, prevalence
National Category
Nursing Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-227303 (URN)10.1515/sjpain-2024-0007 (DOI)001248888700001 ()38887790 (PubMedID)2-s2.0-85196277330 (Scopus ID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2014‐4016Swedish Research Council, 521‐2014‐2715
Available from: 2024-07-03 Created: 2024-07-03 Last updated: 2024-07-03Bibliographically approved
Rankin, L. (2020). Chronic pain: from the study of student attitudes and preferences to the in vitro investigation of a novel treatment strategy. (Doctoral dissertation). Umeå: Umeå universitet
Open this publication in new window or tab >>Chronic pain: from the study of student attitudes and preferences to the in vitro investigation of a novel treatment strategy
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2020. p. 96
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2085
Keywords
HC-PAIRS, best-worst scaling, palmitoylethanolamine, N-acylthanolamines, oral lichen planus, prostaglandins, chronic pain, prolonged pain, chronic pain education, chronic pain management, medical students, attitudes
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:umu:diva-173854 (URN)978-91-7855-268-9 (ISBN)978-91-7855-267-2 (ISBN)
Public defence
2020-09-11, Triple Helix, Samverkanshuset, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2020-08-21 Created: 2020-08-03 Last updated: 2020-08-10Bibliographically approved
Rankin, L., Gouveia-Figueira, S., Danielsson, K. P. & Fowler, C. J. (2020). Relative Deficiency of Anti-Inflammatory N-Acylethanolamines Compared to Prostaglandins in Oral Lichen Planus. Biomedicines, 8(11), Article ID 481.
Open this publication in new window or tab >>Relative Deficiency of Anti-Inflammatory N-Acylethanolamines Compared to Prostaglandins in Oral Lichen Planus
2020 (English)In: Biomedicines, E-ISSN 2227-9059, Vol. 8, no 11, article id 481Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
MDPI, 2020
Keywords
oral lichen planus, palmitoylethanolamide, N-acylethanolamine, prostaglandin, cyclooxygenase-2
National Category
Dentistry
Identifiers
urn:nbn:se:umu:diva-178054 (URN)10.3390/biomedicines8110481 (DOI)000592894000001 ()33172176 (PubMedID)2-s2.0-85096059627 (Scopus ID)
Funder
Region Västerbotten
Available from: 2020-12-30 Created: 2020-12-30 Last updated: 2023-03-24Bibliographically approved
Rankin, L. & Fowler, C. J. (2020). The Basal Pharmacology of Palmitoylethanolamide. International Journal of Molecular Sciences, 21(21), Article ID 7942.
Open this publication in new window or tab >>The Basal Pharmacology of Palmitoylethanolamide
2020 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 21, no 21, article id 7942Article, review/survey (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
MDPI, 2020
Keywords
palmitoylethanolamide, peroxisome proliferator-activated receptor-&#945, fatty acid amide hydrolase, N-acylethanolamine acid amidase, low back pain&#8211, sciatica, atopic eczema
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:umu:diva-177805 (URN)10.3390/ijms21217942 (DOI)000589160300001 ()33114698 (PubMedID)2-s2.0-85093948487 (Scopus ID)
Available from: 2020-12-28 Created: 2020-12-28 Last updated: 2023-03-23Bibliographically approved
Alhouayek, M., Rankin, L., Gouveia-Figueira, S. C. & Fowler, C. J. (2019). Interferon γ treatment increases endocannabinoid and related N-acylethanolamine levels in T84 human colon carcinoma cells. Paper presented at 8th European Workshop on Cannabinoid Research, Roehampton, England, United Kingdom, 31 August - 2 September, 2017. British Journal of Pharmacology, 176(10), 1470-1480
Open this publication in new window or tab >>Interferon γ treatment increases endocannabinoid and related N-acylethanolamine levels in T84 human colon carcinoma cells
2019 (English)In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 176, no 10, p. 1470-1480Article in journal (Refereed) Published
Abstract [en]

Background and purpose: Endocannabinoids and related N-acylethanolamines (NAEs) are involved in regulation of gut function, but relatively little is known as to whether inflammatory cytokines such as IFN affect their levels. We have investigated this in vitro using cultures of T84 colon cancer cells.

Experimental approach: T84 cells, when cultured in monolayers, differentiate to form adult colonic crypt-like cells with excellent permeability barrier properties. The integrity of the permeability barrier in these monolayers was measured using transepithelial electrical resistance (TEER). NAE levels were determined by ultra-performance liquid chromatography-tandem mass spectrometric analysis. Expression of the enzymes involved in NAE and 2-arachidonoylglycerol (2-AG) turnover were assessed with qPCR.

Key results: IFN treatment for 8 or 24h increased levels of both endocannabinoids (anandamide and 2-AG) and the related NAEs. The treatment did not affect the rate of hydrolysis of either anandamide or palmitoylethanolamide by intact cells, and in both cases, fatty acid amide hydrolase (FAAH) rather than NAE-hydrolysing acid amidase (NAAA) was mainly responsible for the hydrolysis of these NAEs. IFN treatment reduced the TEER of the cells in a manner that was not prevented by inhibition of either FAAH or NAAA but was partially reversed by apical administration of the NAE palmitoylethanolamide.

Conclusion and implications: IFN treatment mobilized endocannabinoid and related NAE levels in T84 cells. However, blockade of anandamide or NAE hydrolysis was insufficient to negate the deleterious effects of this cytokine upon the permeability barrier of the cell monolayers.

National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:umu:diva-159393 (URN)10.1111/bph.14135 (DOI)000466968400010 ()29313885 (PubMedID)2-s2.0-85041293990 (Scopus ID)
Conference
8th European Workshop on Cannabinoid Research, Roehampton, England, United Kingdom, 31 August - 2 September, 2017
Available from: 2019-06-10 Created: 2019-06-10 Last updated: 2023-03-24Bibliographically approved
Rankin, L., Fowler, C. J., Stålnacke, B.-M. & Gallego, G. (2019). What influences chronic pain management?: A best-worst scaling experiment with final year medical students and general practitioners. British Journal of Pain, 13(4), 214-225
Open this publication in new window or tab >>What influences chronic pain management?: A best-worst scaling experiment with final year medical students and general practitioners
2019 (English)In: British Journal of Pain, ISSN 2049-4637, Vol. 13, no 4, p. 214-225Article in journal (Refereed) Published
Abstract [en]

Background: Chronic pain education is an essential determinant for optimal chronic pain management. Given that attitudes and preferences are involved in making treatment decisions, identifying which factors are most influential to final year medical students’ and general practitioners’ (GPs) chronic pain management choices is of importance. This study investigates Swedish and Australian students’ preferences with respect to a chronic pain condition, using a best–worst scaling (BWS) experiment, which is designed to rank alternatives.

Methods: BWS, a stated-preference method grounded in random utility theory, was used to explore the importance of factors influencing chronic pain management.

Results: All three cohorts considered the patients’ pain description and previous treatment experience as the most important factors in making treatment decisions, whereas their demographics and voices or facial expressions while describing their pain were considered least important. Factors such as social support, patient preferences and treatment adherence were, however, disregarded by all cohorts in favour of pain assessment factors such as pain ratings, description and history. Swedish medical students and GPs show very high correlation in their choices, although the GPs consider their professional experience as more important compared to the students.

Conclusion: This study suggests that the relative importance of treatment factors is cemented early and thus underline the critical importance of improving pain curricula during undergraduate medical education.

Keywords
Pain management, pain education, best-worst scaling, medical students, general practitioners
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-165668 (URN)10.1177/2049463719832331 (DOI)000489776800003 ()31656627 (PubMedID)2-s2.0-85062322455 (Scopus ID)
Funder
Swedish Research Council, 12158
Available from: 2019-12-06 Created: 2019-12-06 Last updated: 2023-03-24Bibliographically approved
Rankin, L., Stålnacke, B.-M., Fowler, C. J. & Gallego, G. (2018). Differences in Swedish and Australian medical student attitudes and beliefs about chronic pain, its management, and the way it is taught. Scandinavian Journal of Pain, 18(3), 533-544
Open this publication in new window or tab >>Differences in Swedish and Australian medical student attitudes and beliefs about chronic pain, its management, and the way it is taught
2018 (English)In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 18, no 3, p. 533-544Article in journal (Refereed) Published
Abstract [en]

Background and aims: Medical students receive training in the management of chronic pain, but the training is often suboptimal. Considering that the basis for physician’s knowledge is their medical education, it is important to explore the attitudes and beliefs of medical students with respect both to chronic pain management and to their views on current pain education. Therefore, the aim of this study was to compare Swedish and Australian medical student’s attitudes and beliefs about patients with chronic pain, and their perceptions regarding their chronic pain management education.

Methods: An online survey was conducted with final year Australian and Swedish medical students from two different universities between December 2016 and February 2017. Attitudes and beliefs towards chronic pain patients were measured using the Health Care Providers’ Pain and Impairment Scale (HC-PAIRS). A thematic analysis was conducted on open end questions regarding their views on their education and important skills for chronic pain management.

Results: A total of 57 Swedish and 26 Australian medical students completed the HC-PAIRS scale. The Swedish medical students showed statistically significantly lower total mean HC-PAIRS scores compared to Australian medical students (46 and 51, respectively). Australian students had statistically significantly higher scores than the Swedish students for two of four factors: functional expectations and need for cure, whereas no significant differences were seen for the factors social expectations or for projected cognition. From the open end questions it was evident that final year medical students are knowledgeable about key chronic pain items described in clinical guidelines. However, both cohorts described their chronic pain training as poor and in need of improvement in several areas such as more focus on the biopsychosocial model, working in multidisciplinary teams, seeing chronic pain patients and pharmacological training.

Conclusions: Attitudes and beliefs are formed during medical education, and our study exploring attitudes of medical students towards chronic pain and how it is taught have provided valuable information. Our survey provided detailed and cohesive suggestions for education improvement that also are in line with current clinical guidelines. This study indicates that the Swedish final year students have a more positive attitude towards chronic pain patients compared to their Australian counterparts. The majority of students in both cohorts perceived chronic pain management education in need of improvement.

Implications: This study highlights several areas of interest that warrant further investigation, for example, the impact of a changed medical curriculum in alignment with these clinical guidelines requested by students in this survey, and correspondingly if their attitudes towards chronic pain patients can be improved through education. Further, we conclude that it would be valuable to align the implementation of the HC-PAIRS instrument in order to achieve comparable results between future studies.

Place, publisher, year, edition, pages
Walter de Gruyter, 2018
Keywords
HC-PAIRS; attitudes; chronic pain; medical education; medical students
National Category
Other Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-148376 (URN)10.1515/sjpain-2018-0039 (DOI)000439314200023 ()2-s2.0-85046714083 (Scopus ID)
Funder
Swedish Research Council, 12158
Available from: 2018-06-04 Created: 2018-06-04 Last updated: 2023-03-24Bibliographically approved
Gabrielsson, L., Gouveia-Figueira, S., Häggström, J., Alhouayek, M. & Fowler, C. J. (2017). The anti-inflammatory compound palmitoylethanolamide inhibits prostaglandin and hydroxyeicosatetraenoic acid production by a macrophage cell line. Pharmacology Research & Perspectives, 5(2), Article ID e00300.
Open this publication in new window or tab >>The anti-inflammatory compound palmitoylethanolamide inhibits prostaglandin and hydroxyeicosatetraenoic acid production by a macrophage cell line
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2017 (English)In: Pharmacology Research & Perspectives, E-ISSN 2052-1707, Vol. 5, no 2, article id e00300Article in journal (Refereed) Published
Abstract [en]

The anti-inflammatory agent palmitoylethanolamide (PEA) reduces cyclooxygenase (COX) activity in vivo in a model of inflammatory pain. It is not known whether the compound reduces prostaglandin production in RAW264.7 cells, whether such an action is affected by compounds preventing the breakdown of endogenous PEA, whether other oxylipins are affected, or whether PEA produces direct effects upon the COX-2 enzyme. RAW264.7 cells were treated with lipopolysaccharide and interferon-c to induce COX-2. At the level of mRNA, COX-2 was induced > 1000-fold following 24 h of the treatment. Coincubation with PEA (10 mu mol/L) did not affect the levels of COX-2, but reduced the levels of prostaglandins D-2 and E-2 as well as 11- and 15-hydroxyeicosatetraenoic acid, which can also be synthesised by a COX-2 pathway in macrophages. These effects were retained when hydrolysis of PEA to palmitic acid was blocked. Linoleic acidderived oxylipin levels were not affected by PEA. No direct effects of PEA upon the oxygenation of either arachidonic acid or 2-arachidonoylglycerol by COX-2 were found. It is concluded that in lipopolysaccharide and interferon-c-stimulated RAW264.7 cells, PEA reduces the production of COX-2-derived oxylipins in a manner that is retained when its metabolism to palmitic acid is inhibited.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
Palmitoylethanolamide, cyclooxygenase, prostaglandin, oxylipin, RAW264.7 cells, fatty acid amide drolase, N-acylethanolamine hydrolysing acid amidase, bootstrapped linear model
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:umu:diva-140988 (URN)10.1002/prp2.300 (DOI)000407444900009 ()28357126 (PubMedID)2-s2.0-85021909304 (Scopus ID)
Funder
Swedish Research Council, 12158
Available from: 2017-10-25 Created: 2017-10-25 Last updated: 2024-07-02Bibliographically approved
Gabrielsson, L., Mattsson, S. & Fowler, C. J. (2016). Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy. British Journal of Clinical Pharmacology, 82(4), 932-942
Open this publication in new window or tab >>Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy
2016 (English)In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 82, no 4, p. 932-942Article, review/survey (Refereed) Published
Abstract [en]

Palmitoylethanolamide (PEA) has been suggested to have useful analgesic properties and to be devoid of unwanted effects. Here, we have examined critically this contention, and discussed available data concerning the pharmacokinetics of PEA and its formulation. Sixteen clinical trials, six case reports/pilot studies and a meta-analysis of PEA as an analgesic have been published in the literature. For treatment times up to 49days, the current clinical data argue against serious adverse drug reactions (ADRs) at an incidence of 1/200 or greater. For treatment lasting more than 60days, the number of patients is insufficient to rule out a frequency of ADRs of less than 1/100. The six published randomized clinical trials are of variable quality. Presentation of data without information on data spread and nonreporting of data at times other than the final measurement were among issues that were identified. Further, there are no head-to-head clinical comparisons of unmicronized vs. micronized formulations of PEA, and so evidence for superiority of one formulation over the other is currently lacking. Nevertheless, the available clinical data support the contention that PEA has analgesic actions and motivate further study of this compound, particularly with respect to head-to-head comparisons of unmicronized vs. micronized formulations of PEA and comparisons with currently recommended treatments.

Keywords
adverse drug reactions, clinical trials, inflammation, pain, pharmacokinetics, Palmitoylethanolamide
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:umu:diva-130060 (URN)10.1111/bcp.13020 (DOI)000383685700004 ()27220803 (PubMedID)2-s2.0-84986296799 (Scopus ID)
Available from: 2017-01-13 Created: 2017-01-11 Last updated: 2024-07-02Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2883-5603

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