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Food pyramid for subjects with chronic pain: foods and dietary constituents as anti-inflammatory and antioxidant agents

  • Mariangela Rondanelli (a1), Milena Anna Faliva (a1), Alessandra Miccono (a2), Maurizio Naso (a1), Mara Nichetti (a1), Antonella Riva (a3), Fabio Guerriero (a4), Manuela De Gregori (a5) (a6), Gabriella Peroni (a1) and Simone Perna (a1)...

Emerging literature suggests that diet constituents may play a modulatory role in chronic pain (CP) through management of inflammation/oxidative stress, resulting in attenuation of pain. We performed a narrative review to evaluate the existing evidence regarding the optimum diet for the management of CP, and we built a food pyramid on this topic. The present review also describes the activities of various natural compounds contained in foods (i.e. phenolic compounds in extra-virgin olive oil (EVO)) listed on our pyramid, which have comparable effects to drug management therapy. This review included 172 eligible studies. The pyramid shows that carbohydrates with low glycaemic index should be consumed every day (three portions), together with fruits and vegetables (five portions), yogurt (125 ml), red wine (125 ml) and EVO; weekly: legumes and fish (four portions); white meat, eggs and fresh cheese (two portions); red or processed meats (once per week); sweets can be consumed occasionally. The food amounts are estimates based on nutritional and practical considerations. At the top of the pyramid there is a pennant: it means that CP subjects may need a specific customised supplementation (vitamin B12, vitamin D, n-3 fatty acids, fibre). The food pyramid proposal will serve to guide dietary intake with to the intent of alleviating pain in CP patients. Moreover, a targeted diet can also help to solve problems related to the drugs used to combat CP, i.e. constipation. However, this paper would be an early hypothetical proposal due to the limitations of the studies.

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* Corresponding author: Dr Simone Perna, email
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1. Tick, H (2015) Nutrition and pain. Phys Med Rehabil Clin N Am 26, 309320.
2. Zhang, JM & An, J (2007) Cytokines, inflammation, and pain. Int Anesthesiol Clin 45, 2737.
3. Hatakeyama, N & Matsuda, N (2014) Alert cell strategy: mechanisms of inflammatory response and organ protection. Curr Pharm Des 20, 57665778.
4. Swieboda, P, Filip, R, Prystupa, A, et al. (2013) Assessment of pain: types, mechanism and treatment. Ann Agric Environ Med 1, 27.
5. Sokol, CL & Luster, AD (2015) The chemokine system in innate immunity. Cold Spring Harb Perspect Biol 7, a016303.
6. Mittal, M, Siddiqui, MR, Tran, K, et al. (2014) Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal 20, 11261167.
7. Pan, MH, Lai, CS, Ho, CT, et al. (2010) Anti-inflammatory activity of natural dietary flavonoids. Food Funct 1, 1531.
8. Libby, P (2006) Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr 83, 456S460S.
9. Brouwers, H, von Hegedus, J, Toes, R, et al. (2015) Lipid mediators of inflammation in rheumatoid arthritis and osteoarthritis. Best Pract Res Clin Rheumatol 29, 741755.
10. Conaghan, PG, Kloppenburg, M, Schett, G, et al. (2014) Osteoarthritis research priorities: a report from a EULAR ad hoc expert committee. Ann Rheum Dis 73, 14421445.
11. Kulkarni, K, Karssiens, T, Kumar, V, et al. (2016) Obesity and osteoarthritis. Maturitas 89, 2228.
12. Aguilar-Valles, A, Inoue, W, Rummel, C, et al. (2015) Obesity, adipokines and neuroinflammation. Neuropharmacology 96, 124134.
13. Emery, CF, Olson, KL, Bodine, A, et al. (2017) Dietary intake mediates the relationship of body fat to pain. Pain 158, 273277.
14. Giugliano, D, Ceriello, A & Esposito, K (2006) The effects of diet on inflammation: emphasis on the metabolic syndrome. J Am Coll Cardiol 48, 677685.
15. Nelson, AD & Camilleri, M (2015) Chronic opioid induced constipation in patients with nonmalignant pain: challenges and opportunities. Therap Adv Gastroenterol 8, 206220.
16. Srebro, D, Vučković, S, Milovanović, A, et al. (2016) Magnesium in pain research: state of the art. Curr Med Chem (epublication 12 December 2016).
17. Bujalska–Zadrozny, M, Tatarkiewicz, J, Kulik, K, et al. (2017) Magnesium enhances opioid-induced analgesia – What we have learnt in the past decades? Eur J Pharm Science 99, 113127.
18. Ledade, SD, Jain, SN, Darji, AA, et al. (2017) Narrative writing: effective ways and best practices. Perspect Clin Res 8, 5862.
19. Howick, J, Chalmers, I, Glasziou, P, et al. (2017) The 2011 Oxford Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence. Oxford Centre for Evidence-Based Medicine. (accessed January 2018).
20. Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione (INRAN) (2003) Linee guida per una sana alimentazione (Guidelines for healthy eating). (accessed January 2018).
21. Perry, BG, Bear, TL, Lucas, SJ, et al. (2016) Mild dehydration modifies the cerebrovascular response to the cold pressor test. Exp Physiol 101, 135142.
22. Bear, T, Philipp, M, Hill, S, et al. (2016) A preliminary study on how hypohydration affects pain perception. Psychophysiology 53, 605610.
23. Parker, Heinking KP & Kappler, RE (2012) Efficacy of osteopathic manipulative treatment for low back pain in euhydrated and hypohydrated conditions: a randomized crossover trial. J Am Osteopath Assoc 112, 276284.
24. Assmann, KE, Lassale, C, Andreeva, VA, et al. (2015) A healthy dietary pattern at midlife, combined with a regulated energy intake, is related to increased odds for healthy aging. J Nutr 145, 21392145.
25. Miller, ER 3rd, Erlinger, TP, Sacks, FM, et al. (2005) A dietary pattern that lowers oxidative stress increases antibodies to oxidized LDL: results from a randomized controlled feeding study. Atherosclerosis 183, 175182.
26. Lopes, HF, Martin, KL, Nashar, K, et al. (2003) DASH diet lowers blood pressure and lipid-induced oxidative stress in obesity. Hypertension 41, 422430.
27. Erlinger, TP, Miller, ER 3rd, Charleston, J, et al. (2003) Inflammation modifies the effects of a reduced fat low-cholesterol diet on lipids: results from the DASH-sodium trial. Circulation 108, 150154.
28. Delichatsios, HK & Welty, FK (2005) Influence of the DASH diet and other low-fat, high-carbohydrate diets on blood pressure. Curr Artheroscler Rep 7, 446454.
29. Bhupathiraju, SN & Tucker, KL (2011) Greater variety in fruit and vegetable intake is associated with lower inflammation in Puerto Rican adults. Am J Clin Nutr 93, 3746.
30. Esmaillzadeh, A, Kimiagar, M, Mehrabi, Y, et al. (2006) Fruit and vegetable intakes, C-reactive protein, and the metabolic syndrome. Am J Clin Nutr 84, 14891497.
31. Oliveira, A, Rodriguez-Artalejo, F & Lopes, C (2009) The association of fruits, vegetables, antioxidant vitamins and fiber intake with high-sensitivity C-reactive protein: sex and body mass index interactions. Eur J Clin Nutr 63, 13451352.
32. Holt, EM, Steffen, LM, Moran, A, et al. (2009) Fruit and vegetable consumption and its relation to markers of inflammation and oxidative stress in adolescents. J Am Diet Assoc 109, 414421.
33. Lührs, H, Gerke, T, Müller, JG, et al. (2002) Butyrate inhibits NF-κB activation in lamina propria macrophages of patients with ulcerative colitis. Scand J Gastroenterol 37, 458466.
34. Suzuki, T & Hara, H (2011) Role of flavonoids in intestinal tight junction regulation. J Nutr Biochem 22, 401408.
35. Dickinson, S, Hancock, DP, Petocz, P, et al. (2008) High glycaemic index carbohydrate increases nuclear factor-κB activation in mononuclear cells of young, lean healthy subjects. Am J Clin Nutr 87, 11881193.
36. Ceriello, A (2005) Postprandial hyperglycemia and diabetes complications: is it time to treat? Diabetes 54, 17.
37. Fardet, A (2010) New hypotheses for the health-protective mechanisms of wholegrain cereals: what is beyond fibre? Nutr Res Rev 23, 65134.
38. Gögebakan, O, Kohl, A, Osterhoff, MA, et al. (2011) Effects of weight loss and long-term weight maintenance with diets varying in protein and glycaemic index on cardiovascular risk factors: the Diet, Obesity, and Genes (DiOGenes) study: a randomized, controlled trial. Circulation 124, 28292838.
39. Ebbeling, CB, Swain, JF, Feldman, HA, et al. (2012) Effects of dietary composition on energy expenditure during weight-loss maintenance. JAMA 307, 26272634.
40. Tripoli, E, Giammanco, M, Tabacchi, G, et al. (2005) The phenolic compounds of olive oil: structure, biological activity and beneficial effects on human health. Nutr Res Rev 18, 98112.
41. Harper, CR, Edwards, MC & Jacobson, TA (2006) Flaxseed oil supplementation does not affect plasma lipoprotein concentration or particle size in human subjects. J Nutr 136, 28442848.
42. Aguilera, CM, Mesa, MD, Ramirez-Tortosa, MC, et al. (2004) Sunflower-seed oil does not protect against LDL oxidation as virgin olive oil does in patients with peripheral vascular disease. Clin Nutr 23, 673681.
43. Owen, RW, Mier, W, Giacosa, A, et al. (2000) Phenolic compounds and squalene in olive oils: the concentration and antioxidant potential of total phenols, simple phenols, secoiridoids, lignans and squalene. Food Chem Toxicol 38, 647659.
44. Owen, RW, Mier, W, Giacosa, A, et al. (2000) Identifications of lignans as major components in the phenolic fraction of olive oil. Clin Chem 46, 976988.
45. Owen, RW, Giacosa, A, Hull, WE, et al. (2000) Olive-oil consumption and health: the possible role of antioxidants. Lancet Oncol 1, 107112.
46. Bendini, A, Cerretani, L, Carrasco-Pancorbo, A, et al. (2007) Phenolic molecules in virgin olive oils: a survey of their sensory properties, health effects, antioxidant activity and analytical methods: an overview of the last decade. Molecules 12, 16791719.
47. Omar, SH (2010) Oleuropein in olive and its pharmacological effects. Sci Pharm 78, 133154.
48. El, SN & Karakaya, S (2009) Olive tree (Olea europaea) leaves: potential beneficial effects on human health. Nutr Rev 67, 632638.
49. Cicerale, S, Lucas, LJ & Keast, RS (2012) Antimicrobial, antioxidant and anti-inflammatory phenolic activities in extra virgin olive oil. Curr Opin Biotechnol 23, 129135.
50. Cicerale, S, Lucas, L & Keast, RS (2010) Biological activities of phenolic compounds present in virgin olive oil. Int J Mol Sci 11, 458479.
51. Visioli, F, Poli, A & Gall, C (2002) Antioxidant and other biological activities of phenols from olives and olive oil. Med Res Rev 22, 6575.
52. Hu, T, He, XW, Jiang, JG, et al. (2014) Hydroxytyrosol and its potential therapeutic effects. J Agric Food Chem 62, 14491455.
53. Omar, SH (2010) Cardioprotective and neuroprotective roles of oleuropein in olive. Saudi Pharm J 18, 111121.
54. Cicerale, S, Conlan, XA, Sinclair, AJ, et al. (2009) Chemistry and health of olive oil phenolics. Crit Rev Food Sci Nutr 49, 218236.
55. Beauchamp, GK, Keast, RS, Morel, D, et al. (2005) Phytochemistry: ibuprofen-like activity in extra-virgin olive oil. Nature 437, 4546.
56. Montedoro, G, Servili, M, Baldioli, M, et al. (1993) Simple and hydrolyzable compounds in virgin olive oil. 3. Spectroscopic characterizations of the secoiridoid derivatives. J Agric Food Chem 41, 22282234.
57. Andrewes, P, Busch, JL, de Joode, T, et al. (2003) Sensory properties of virgin olive oil polyphenols: identification of deacetoxy-ligstroside aglycon as a key contributor to pungency. J Agric Food Chem 51, 14151420.
58. Cicerale, S, Breslin, PA, Beauchamp, GK, et al. (2009) Sensory characterization of the irritant properties of oleocanthal, a natural anti-inflammatory agent in extra virgin olive oils. Chem Senses 34, 333339.
59. Sahranavard, S, Kamalinejad, M & Faizi, M (2014) Evaluation of anti-inflammatory and anti-nociceptive effects of defatted fruit extract of Olea europaea . Iran J Pharm Res 13, 119123.
60. Takeda, R, Koike, T, Taniguchi, I, et al. (2013) Double-blind placebo-controlled trial of hydroxytyrosol of Olea europaea on pain in gonarthrosis. Phytomedicine 20, 861864.
61. Cortés Castell, E, Galindo, CV, Montell, T, et al. (2014) Efecto sobre el neurodesarrollo y neuroprotección en pez cebra de un extracto polifenólico de huesos de aceituna (Effect on neurodevelopment and neuroprotection in zebrafish of a polyphenolic extract of olive pits). Nutr Hosp 30, 338342.
62. Zhao, J, Suyama, A, Chumg, H, et al. (2016) Ferulic acid enhances NO production through up regulation of argininosuccinate synthase in inflammatory human endothelial cells. Life Sci 145, 224232.
63. Suntar, IP, Akkol, EK & Baykal, T (2010) Assessment of anti-inflammatory and antinociceptive activities of Olea europaea L. J Med Food 13, 352356.
64. Seaman, DR (2002) The diet-induced proinflammatory state: a cause of chronic pain and other degenerative diseases? J Manipulative Physiol Ther 25, 168179.
65. Shen, J, Wilmot, KA, Ghasemzadeh, N, et al. (2015) Mediterranean dietary patterns and cardiovascular health. Annu Rev Nutr 35, 425449.
66. Ozawa, M, Shipley, M, Kivimaki, M, et al. (2017) Dietary pattern, inflammation and cognitive decline: The Whitehall II prospective cohort study. Clin Nutr 36, 506512.
67. Nuora, A, Chiang, VS, Milan, AM, et al. (2015) The impact of beef steak thermal processing on lipid oxidation and postprandial inflammation related responses. Food Chem 184, 5764.
68. Maroon, JC & Bost, JW (2006) Omega-3 fatty acids (fish oil) as an anti-inflammatory: an alternative to nonsteroidal anti-inflammatory drugs for discogenic pain. Surg Neurol 65, 326331.
69. Nakamoto, K, Nishinaka, T, Sato, N, et al. (2013) Hypothalamic GPR40 signaling activated by free long chain fatty acids suppresses CFA-induced inflammatory chronic pain. PLOS ONE 8, e81563.
70. Hosseinpour-Niazi, S, Mirmiran, P, Fallah-Ghohroudi, A, et al. (2015) Non-soya legume-based therapeutic lifestyle change diet reduces inflammatory status in diabetic patients: a randomised cross-over clinical trial. Br J Nutr 114, 213219.
71. Salehi-Abargouei, A, Saraf-Bank, S, Bellissimo, N, et al. (2015) Effects of non-soya legume consumption on C-reactive protein: a systematic review and meta-analysis. Nutrition 31, 631639.
72. Martin, H (2010) Role of PPAR-γ in inflammation. Prospects for therapeutic intervention by food components. Mutat Res 690, 5763.
73. Shir, Y, Raja, SN, Weissman, CS, et al. (2001) Consumption of soya diet before nerve injury preempts the development of neuropathic pain in rats. Anesthesiology 95, 12381244.
74. Arjmandi, BH, Khalil, DA, Lucas, EA, et al. (2004) Soya protein may alleviate osteoarthritis symptoms. Phytomedicine 11, 567575.
75. Hooshmand, S, Soung do, Y, Lucas, EA, et al. (2007) Genistein reduces the production of proinflammatory molecules in human chondrocytes. J Nutr Biochem 18, 609614.
76. Stecher, B (2015) The roles of inflammation, nutrient availability and the commensal microbiota in enteric pathogen infection. Microbiol Spectr 3, (epublication 11 June 2015).
77. Harmsen, HJ, Raangs, GC, He, T, et al. (2002) Extensive set of 16S rRNA-based probes for detection of bacteria in human feces. Appl Environ Microbiol 68, 2982–2890.
78. Mayer, EA, Knight, R, Mazmanian, SK, et al. (2014) Gut microbes and the brain: paradigm shift in neuroscience. J Neurosci 34, 1549015496.
79. Chang, MC, Fan, SZ, Hsiao, PN, et al. (2011) Influence of morphine on host immunity. Acta Anaesthesiol Taiwan 49, 105108.
80. Roy, S, Ninkovic, J, Banerjee, S, et al. (2011) Opioid drug abuse and modulation of immune function: consequences in the susceptibility to opportunistic infections. J Neuroimmune Pharmacol 6, 442465.
81. Banerjee, S, Sindberg, G, Wang, F, et al. (2016) Opioid-induced gut microbial disruption and bile dysregulation leads to gut barrier compromise and sustained systemic inflammation. Mucosal Immunol 9, 14181428.
82. FAO/WHO (2002) Joint FAO/WHO Working Group Report on Drafting Guidelines for the Evaluation of Probiotics in Food. London, Canada: FAO/WHO.
83. Bosscher, D, Breynaert, A, Pieters, L, et al. (2009) Food-based strategies to modulate the composition of the intestinal microbiota and their associated health effects. J Physiol Pharmacol 60, 511.
84. Kapoor, S (2008) Management of constipation in the elderly: emerging therapeutic strategies. World J Gastroenterol 14, 52265227.
85. Pei, R, Martin, DA, Di Marco, DM, et al. (2017) Evidence for the effects of yogurt on gut health and obesity. Crit Rev Food Sci Nutr 57, 15691583.
86. Meng, H, Ba, Z, Lee, Y, et al. (2017) Consumption of Bifidobacterium animalis subsp. lactis BB-12 in yogurt reduced expression of TLR-2 on peripheral blood-derived monocytes and pro-inflammatory cytokine secretion in young adults. Eur J Nutr 56, 649661.
87. Klein, A, Friedrich, U, Vogelsang, H, et al. (2008) Lactobacillus acidophilus 74-2 and Bifidobacterium animalis subsp lactis DGCC 420 modulate unspecific cellular immune response in healthy adults. Eur J Clin Nutr 62, 584593.
88. Patel, S (2015) Emerging trends in nutraceutical applications of whey protein and its derivatives. J Food Sci Technol 52, 68476858.
89. Cady, RJ, Hirst, JJ & Durham, PL (2010) Dietary grape seed polyphenols repress neuron and glia activation in trigeminal ganglion and trigeminal nucleus caudalis. Mol Pain 6, 91.
90. Woo, YJ, Joo, YB & Jung, YO (2011) Grape seed proanthocyanidin extract ameliorates monosodium iodoacetate-induced osteoarthritis. Exp Mol Med 43, 561570.
91. Zhao, G, Etherton, TD, Martin, KR, et al. (2004) Dietary α-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in hypercholesterolemic men and women. J Nutr 134, 29912997.
92. Zhao, G, Etherton, TD, Martin, KR, et al. (2007) Dietary α-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects. Am J Clin Nutr 85, 385391.
93. Song, Y, Ridker, PM, Manson, JE, et al. (2005) Magnesium intake, C-reactive protein, and the prevalence of metabolic syndrome in middle-aged and older U.S. women. Diabetes Care 28, 14381444.
94. Shechter, M, Sharir, M, Labrador, MJ, et al. (2000) Oral magnesium therapy improves endothelial function in patients with coronary artery disease. Circulation 102, 23532358.
95. Ros, E, Núñez, I, Pérez-Heras, A, et al. (2004) A walnut diet improves endothelial function in hypercholesterolemic subjects: a randomized crossover trial. Circulation 109, 16091614.
96. Wells, BJ, Mainous, AG & Everett, CJ (2005) Association between dietary arginine and C-reactive protein. Nutrition 21, 125130.
97. Bulló, M, Juanola-Falgarona, M, Hernández-Alonso, P, et al. (2015) Nutrition attributes and health effects of pistachio nuts. Br J Nutr 113, S79S93.
98. Sari, I, Baltaci, Y, Bagci, C, et al. (2010) Effect of pistachio diet on lipid parameters, endothelial function, inflammation, and oxidative status: a prospective study. Nutrition 26, 399404.
99. Faintuch, J, Horie, LM, Barbeiro, HV, et al. (2007) Systemic inflammation in morbidly obese subjects: response to oral supplementation with α-linolenic acid. Obes Surg 17, 341347.
100. Imaeda, N, Tokudome, Y, Ikeda, M, et al. (1999) Foods contributing to absolute intake and variance in intake of selected vitamins, minerals and dietary fiber in middle-aged Japanese. J Nutr Sci Vitaminol 45, 519532.
101. Chang, D (2004) Effect of pumpkin distillable subject on lipid peroxidation and the activity of antioxidative enzyme induced by Plumbum in mouse [article in Chinese]. Chin J Clin Rehabil 8, 43784379.
102. Fahim, AT, Abd-el Fattah, AA, Agha, AM, et al. (1995) Effect of pumpkin-seed oil on the level of free radical scavengers induced during adjuvant-arthritis in rats. Pharmacol Res 31, 7379.
103. Oliviero, F, Spinella, P, Fiocco, U, et al. (2015) How the Mediterranean diet and some of its components modulate inflammatory pathways in arthritis. Swiss Med Wkly 145, w14190.
104. Casas, R, Sacanella, E & Estruch, R (2014) The immune protective effect of the Mediterranean diet against chronic low-grade inflammatory diseases. Endocr Metab Immune Disord Drug Targets 14, 245254.
105. Lakhan, SE, Ford, CT & Tepper, D (2015) Zingiberaceae extracts for pain: a systematic review and meta-analysis. Nutr J 14, 50.
106. Hu, X, Huang, F, Szymusiak, M, et al. (2016) PLGA-curcumin attenuates opioid-induced hyperalgesia and inhibits spinal CaMKIIα. PLOS ONE 11, e0146393.
107. Salas, MM, Cheppudira, BP, Fowler, M, et al. (2014) Analgesic and anti-inflammatory properties of curcumin: application for burn wounds. In Curcumin: Synthesis, Emerging Role in Pain Management and Health Implications, pp 255280 [DL Pouliquen, editor]. New York: Nova Biomedical.
108. Chopra, A, Saluja, M, Tillu, G, et al. (2013) Ayurvedic medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee osteoarthritis: a randomized, double-blind, controlled equivalence drug trial. Rheumatology (Oxford) 52, 14081417.
109. Vriens, J, Nilius, B & Vennekens, R (2008) Herbal compounds and toxins modulating TRP channels. Curr Neuropharmacol 6, 7996.
110. Semwal, RB, Semwal, DK, Combrinck, S, et al. (2015) Gingerols and shogaols: important nutraceutical principles from ginger. Phytochemistry 117, 554568.
111. Dedov, VN, Tran, VH, Duke, CC, et al. (2002) Gingerols: a novel class of vanilloid receptor (VR1) agonists. Br J Pharmacol 137, 793798.
112. Klauke, AL, Racz, I, Pradier, B, et al. (2014) The cannabinoid CB2 receptor-selective phytocannabinoid β-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. Eur Neuropsychopharmacol 24, 608620.
113. Treede, I, Braun, A, Sparla, R, et al. (2007) Anti-inflammatory effects of phosphatidylcholine. J Biol Chem 282, 2715527164.
114. Treede, I, Braun, A, Jeliaskova, P, et al. (2009) TNF-α-induced up-regulation of pro-inflammatory cytokines is reduced by phosphatidylcholine in intestinal epithelial cells. BMC Gastroenterol 9, 53.
115. Andersen, CJ (2015) Bioactive egg components and inflammation. Nutrients 7, 78897913.
116. Ballesteros, MN, Valenzuela, F, Robles, AE, et al. (2015) One egg per day improves inflammation when compared to an oatmeal-based breakfast without increasing other cardiometabolic risk factors in diabetic patients. Nutrients 7, 34493463.
117. Drehmer, M, Pereira, MA, Schmidt, MI, et al. (2016) Total and full-fat, but not low-fat, dairy product intakes are inversely associated with metabolic syndrome in adults. J Nutr 146, 8189.
118. Bounous, G, Batist, G & Gold, P (1991) Whey proteins in cancer prevention. Cancer Lett 57, 9194.
119. Schmidt, A, Petry, N, Walther, B, et al. (2015) Inflammatory and metabolic responses to high-fat meals with and without dairy products in men. Br J Nutr 113, 18531861.
120. Demmer, E, Van Loan, MD, Rivera, N, et al. (2016) Consumption of a high-fat meal containing cheese compared with a vegan alternative lowers postprandial C-reactive protein in overweight and obese individuals with metabolic abnormalities: a randomised controlled cross-over study. J Nutr Sci 5, e9.
121. Dugan, CE, Aguilar, D, Park, YK, et al. (2016) Dairy consumption lowers systemic inflammation and liver enzymes in typically low-dairy consumers with clinical characteristics of metabolic syndrome. J Am Coll Nutr 35, 255261.
122. Bordoni, A, Danesi, F, Dardevet, D, et al. (2017) Dairy products and inflammation: a review of the clinical evidence. Crit Rev Food Sci Nutr 57, 24972525.
123. Rocha, DM, Caldas, AP, Oliveira, LL, et al. (2016) Saturated fatty acids trigger TLR4-mediated inflammatory response. Atherosclerosis 244, 211215.
124. Van Meji, LE & Mensink, RP (2010) Effects of low-fat dairy consumption on markers of low-grade systemic inflammation and endothelial function in overweight and obese subjects: an intervention study. Br J Nutr 104, 15231527.
125. Giacosa, A, Barale, R, Bavaresco, L, et al. (2016) Mediterranean way of drinking and longevity. Crit Rev Food Sci Nutr 56, 635640.
126. Giacosa, A, Adam-Blondon, AF, Baer-Sinnott, S, et al. (2012) Alcohol and wine in relation to cancer and other diseases. Eur J Cancer Prev 21, 103108.
127. Kida, Y & Goligorsky, MS (2015) Sirtuins, cell senescence, and vascular aging. Can J Cardiol 32, 634641.
128. Middleton, E & Kandaswami, C (1992) Effects of flavonoids on immune and inflammatory cell functions. Biochem Pharmacol 43, 11671179.
129. Middleton, E Jr (1998) Effect of plant flavonoids on immune and inflammatory cell function. Adv Exp Med Biol 439, 175182.
130. Tunon, MJ, Garcia-Mediavilla, MV, Sanchez-Campos, S, et al. (2009) Potential of flavonoids as antiinflammatory agents: modulation of pro-inflammatory gene expression and signal transduction pathways. Curr Drug Metab 10, 256271.
131. Manthey, JA (2000) Biological properties of flavonoids pertaining to inflammation. Microcirculation 7, S29S34.
132. Grannados-Soto, V, Argulles, CF & Ortiz, MI (2002) The peripheral antinociceptive effect of resveratrol is associated with activation of potassium channels. Neuropharmacology 43, 917923.
133. Kim, HI, Kim, TH & Song, JH (2005) Resveratrol inhibits Na+ currents in rat dorsal root ganglion neurons. Brain Res 1045, 134141.
134. Liew, R, Stagg, MA, MacLeod, KT, et al. (2005) The red wine polyphenol, resveratrol, exerts acute direct action on guinea-pig ventricular myocytes. Eur J Pharmacol 519, 18.
135. Gao, ZB & Hu, GY (2005) Trans-resveratrol, a red wine ingredient, inhibits voltage-activated potassium currents in rat hippocampal neurons. Brain Res 1056, 6875.
136. Yu, L, Wang, S, Kogure, Y, et al. (2013) Modulation of TRP channels by resveratrol and other stilbenoids. Mol Pain 9, 3.
137. Kwan, KY, Glazer, JM, Corey, DP, et al. (2009) TRPA1 modulates mechano transduction in cutaneous sensory neurons. J Neurosci 29, 48084819.
138. Gao, ZB, Chen, XQ & Hu, GY (2006) Inhibition of excitatory synaptic transmission by trans-resveratrol in rat hippocampus. Brain Res 1111, 4147.
139. Takehana, S, Sekiguchi, K, Inoue, M, et al. (2016) Systemic administration of resveratrol suppress the nociceptive neuronal activity of spinal trigeminal nucleus caudalis in rats. Brain Res Bull 120, 117122.
140. Fields, E (2008) History of modified-release morphine and opioid/antagonist combinations. (accessed January 2018).
141. Carson, S, Thakurta, S, Low, A, et al. (2011) Drug Class Review: Long-Acting Opioid Analgesics: Final Update 6 Report. Portland, OR: Oregon Health and Science University.
142. Fiske, WD, Jobes, J, Xiang, Q, et al. (2012) The effects of ethanol on the bioavailability of oxymorphone extended-release tablets and oxymorphone crush-resistant extended-release tablets. J Pain 13, 9099.
143. Sathyan, G, Sivakumar, K & Thipphawong, J (2008) Pharmacokinetic profile of a 24-hour controlled-release OROS formulation of hydromorphone in the presence of alcohol. Curr Med Res Opin 24, 297305.
144. Johnson, FK, Ciric, S, Boudriau, S, et al. (2012) Effects of alcohol on the pharmacokinetics of morphine sulfate and naltrexone hydrochloride extended release capsules. J Clin Pharmacol 52, 747756.
145. Hakkinen, M, Launiainen, T, Vuori, E, et al. (2012) Comparison of fatal poisonings by prescription opioids. Forensic Sci Int 222, 327331.
146. Webster, LR, Cochella, S, Dasgupta, N, et al. (2011) An analysis of the root causes for opioid-related overdose deaths in the United States. Pain Med 12, S26S35.
147. Ali, NA, Marshall, RW, Allen, EM, et al. (1985) Comparison of the effects of therapeutic doses of meptazinol and a dextropropoxyphene/paracetamol mixture alone and in combination with ethanol on ventilatory function and saccadic eye movements. Br J Clin Pharmacol 20, 631637.
148. Saunders, KW, Von Korff, M, Campbell, CI, et al. (2012) Concurrent use of alcohol and sedatives among persons prescribed chronic opioid therapy: prevalence and risk factors. J Pain 13, 266275.
149. Wenghofer, EF, Wilson, L, Kahan, M, et al. (2011) Survey of Ontario primary care physicians’ experiences with opioid prescribing. Can Fam Physician 57, 324332.
150. Weathermon, R & Crabb, DW (1999) Alcohol and medication interactions. Alcohol Res Health 23, 4054.
151. Defagó, MD, Elorriaga, N, Irazola, VE, et al. (2014) Influence of food patterns on endothelial biomarkers: a systematic review. J Clin Hypertens (Greenwich) 16, 907913.
152. Lopez-Garcia, E, Schulze, MB, Fung, TT, et al. (2004) Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction. Am J Clin Nutr 80, 10291035.
153. Nettleton, JA, Steffen, LM, Mayer-Davis, EJ, et al. (2006) Dietary patterns are associated with biochemical markers of inflammation and endothelial activation in the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr 83, 13691379.
154. Katz, DL, Doughty, K & Ali, A (2011) Cocoa and chocolate in human health and disease. Antioxid Redox Signal 15, 27792811.
155. di Giuseppe, R, Di Castelnuovo, A, Centritto, F, et al. (2008) Regular consumption of dark chocolate is associated with low serum concentrations of C-reactive protein in a healthy Italian population. J Nutr 138, 19391945.
156. Thomas, CM & Campbell, P (2015) Vitamin D supplementation for pain. US Pharm 40, 4346.
157. McCabe, PS, Pye, SR, Beth, JM, et al. (2016) Low vitamin D and the risk of developing chronic widespread pain: results from the European male ageing study. BMC Musculoskelet Disord 17, 32.
158. Costan, AR, Vulpoi, C & Mocanu, V (2014) Vitamin D fortified bread improves pain and physical function domains of quality of life in nursing home residents. J Med Food 17, 625631.
159. Von Kanel, R, Müller-Hartmannsgruber, V, Kokinogenis, G, et al. (2014) Vitamin D and central hypersensitivity in patients with chronic pain. Pain Med 15, 16091618.
160. Haroon, M & Fitzgerald, O (2012) Vitamin D and its emerging role in immunopathology. Clin Rheumatol 31, 199202.
161. Shipton, EE & Shipton, EA (2015) Vitamin D deficiency and pain: clinical evidence of low levels of vitamin D and supplementation in chronic pain states. Pain Ther 4, 6787.
162. Straube, S, Derry, S & Straube, C (2015) Vitamin D for the treatment of chronic painful conditions in adults. Cochrane Database Syst Rev, issue 5, CD007771.
163. Ghazanfari, S, Imenshahidi, M, Etemad, L, et al. (2014) Effect of cyanocobalamin (vitamin B12) in the induction and expression of morphine tolerance and dependence in mice. Drug Res 64, 113117.
164. Hosseinzadeh, H, Moallem, SA, Moshiri, M, et al. (2012) Anti-nociceptive and anti-inflammatory effects of cyanocobalamin (vitamin B12) against acute and chronic pain and inflammation in mice. Arzneimittelforschung 62, 324329.
165. Chiu, CK, Low, TH, Tey, YS, et al. (2011) The efficacy and safety of intramuscular injections of methylcobalamin in patients with chronic nonspecific low back pain: a randomized controlled trial. Singapore Med J 52, 868873.
166. Freitas, RD, Costa, KM, Nicoletti, NF, et al. (2016) Omega-3 fatty acids are able to modulate the painful symptoms associated to cyclophosphamide-induced-hemorrhagic cystitis in mice. J Nutr Biochem 27, 219232.
167. Wagner, K, Vito, S, Inceoglu, B, et al. (2014) The role of long chain fatty acids and their epoxide metabolites in nociceptive signaling. Prostaglandins Other Lipid Mediat 113–115, 212.
168. Escudero, GE, Romañuk, CB, Toledo, ME, et al. (2015) Analgesia enhancement and prevention of tolerance to morphine: beneficial effects of combined therapy with omega-3 fatty acids. J Pharm Pharmacol 67, 12511262.
169. Boe, C & Vangsness, T (2015) Fish oil and osteoarthritis: current evidence. Am J Orthop 44, 302305.
170. Stanghellini, V, Bellacosa, L & Cogliandro, R (2013) Fiber and macrogol in the therapy of chronic constipation. Minerva Gastroenterol Dietol 59, 217230.
171. Slavin, JL (2008) Position of the American Dietetic Association: health implications of dietary fiber. J Am Diet Assoc 108, 17161731.
172. Longstreth, GF, Thompson, WG, Chey, WD, et al. (2006) Functional bowel disorders. Gastroenterology 130, 14801491.
173. Reimer, K, Hopp, M, Zenz, M, et al. (2009) Meeting the challenges of opioid-induced constipation in chronic pain management – a novel approach. Pharmacology 83, 1017.
174. Davis, MP (2005) The opioid bowel syndrome: a review of pathophysiology and treatment. J Opioid Manag 1, 153161.
175. Holzer, P (2007) Treatment of opioid-induced gut dysfunction. Expert Opin Investig Drugs 16, 181194.
176. Trinkley, KE, Sill, BE, Porter, K, et al. (2015) Prescribing patterns for outpatient treatment of constipation, irritable bowel syndrome-related constipation, and opioid-induced constipation: a retrospective cross-sectional study. J Manag Care Pharm 21, 10771087.
177. Wan, Y, Corman, S, Gao, X, et al. (2015) Economic burden of opioid-induced constipation among long-term opioid users with noncancer pain. Am Health Drug Benefits 8, 93102.
178. Gaertner, J, Siemens, W, Camilleri, M, et al. (2015) Definitions and outcome measures of clinical trials regarding opioid-induced constipation: a systematic review. J Clin Gastroenterol 49, 916.
179. Jones, R, Prommer, E & Backstedt, D (2015) Naloxegol: a novel therapy in the management of opioid-induced constipation. Am J Hosp Palliat Care 33, 875880.
180. Kane-Gill, SL, Rubin, EC, Smithburger, PL, et al. (2014) The cost of opioid-related adverse drug events. J Pain Palliat Care Pharmacother 28, 282293.
181. Candrilli, SD, Davis, KL & Iyer, S (2009) Impact of constipation on opioid use patterns, health care resource utilization, and costs in cancer patients on opioid therapy. J Pain Palliat Care Pharmacother 23, 231241.
182. Addington-Hall, J, Altmann, D & McCarthy, M (1998) Which terminally ill cancer patients receive hospice in-patient care? Soc Sci Med 46, 10111016.
183. McMillan, SC & Tittle, M (1995) A descriptive study of the management of pain and pain-related side effects in a cancer center and a hospice. Hosp J 10, 89108.
184. Tittle, M & McMillan, SC (1994) Pain and pain-related side effects in an ICU and on a surgical unit: nurses’ management. Am J Crit Care 3, 2530.
185. Addington-Hall, JM, MacDonald, LD, Anderson, HR, et al. (1991) Dying from cancer: the views of the bereaved family and friends about the experiences of terminally ill patients. Palliat Med 5, 207214.
186. Walsh, TD (1984) Oral morphine in chronic cancer pain. Pain 18, 111.
187. Vainio, A & Auvinen, A (1996) Prevalence of symptoms among patients with advanced cancer: an international collaborative study. J Pain Symptom Manage 12, 310.
188. Donnelly, S, Walsh, D & Rybicki, L (1995) The symptoms of advanced cancer: identification of clinical and research priorities by assessment of prevalence and severity. J Palliat Care 11, 2732.
189. Weitzner, MA, Moody, LN & McMillan, SC (1997) Symptom management issues in hospice care. Am J Hosp Palliat Care 14, 190195.
190. McMillan, SC (2002) Presence and severity of constipation in hospice patients with advanced cancer. Am J Hosp Palliat Care 19, 426430.
191. McMillan, SC & Weitzner, M (2000) How problematic are various aspects of quality of life in patients with cancer at the end of life? Oncol Nurs Forum 27, 817823.
192. Barros-Neto, JA, Souza-Machado, A, Kraychete, DC, et al. (2010) Comprometimento da integridade intestinal na fibromialgia e sindrome dolorosa miofascial: uma revisão (Impairment of intestinal integrity in fibromyalgia and myofascial pain syndrome: a review). Rev Ciênc Méd Biol 10, 246253.
193. McMillan, SC & Small, BJ (2002) Symptom distress and quality of life in patients with cancer newly admitted to hospice homecare. Oncol Nurs Forum 29, 14211428.
194. Prichard, D, Norton, C & Bharucha, AE (2016) Management of opioid-induced constipation. Br J Nurs 25, S4S11.
195. Nelson, AD & Camilleri, M (2016) Opioid-induced constipation: advances and clinical guidance. Ther Adv Chronic Dis 7, 121134.
196. Stannard, C (2016) Opioids and chronic pain: using what we know to change what we do. Curr Opin Support Palliat Care 10, 129136.
197. Kurz, A & Sessler, DI (2003) Opioid-induced bowel dysfunction: pathophysiology and potential new therapies. Drugs 63, 649671.
198. Portenoy, RK & Derby, S (1997) Assessment and management of opioid-induced constipation. In Topics in Palliative Care, vol. 1, pp. 95112 [RK Portenoy and E Bruera, editors]. New York: Oxford University Press.
199. Robinson, CB, Fritch, M, Hullett, L, et al. (2000) Development of a protocol to prevent opioid-induced constipation in patients with cancer: a research utilization project. Clin J Oncol Nurs 4, 7984.
200. Mounsey, A, Raleigh, M & Wilson, A (2015) Management of constipation in older adults. Am Fam Physician 92, 500504.
201. Niwa, T, Nakao, M, Hoshi, S, et al. (2002) Effect of dietary fiber on morphine-induced constipation in rats. Biosci Biotechnol Biochem 66, 12331240.
202. Li, Y, Zong, Y, Qi, J, et al. (2011) Prebiotics and oxidative stress in constipated rats. J Pediatr Gastroenterol Nutr 53, 447452.
203. National Cancer Institute (2017) Gastrointestinal Complications (PDQ®)–Health Professional Version. (accessed January 2018).
204. Fraga, CG (2005) Relevance, essentiality and toxicity of trace elements in human health. Mol Aspects Med 26, 235244.
205. McCall, KA, Huang, C-C & Fierke, CA (2005) Function and mechanism of zinc metalloenzymes. ASNS 26, 235244.
206. Osredkar, J & Sustar, N (2011) Copper and zinc, biological role and significance of copper/zinc imbalance. J Clin Toxicol S3, 001.
207. Dhawan, DK & Chadha, VD (2010) Zinc: a promising agent in dietary chemoprevention of cancer. Indian J Med Res 132, 676682.
208. Bonaventura, P, Benedetti, G, Albaredè, F, et al. (2015) Zinc and its role in immunity and inflammation. Autoimmun Rev 14, 277285.
209. Wong, CP, Rinaldi, NA & Ho, E (2015) Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation. Mol Nutr Food Res 59, 991999.
210. Liu, T, Walker, JS & Tracey, DJ (1999) Zinc alleviates thermal hyperalgesia due to partial nerve injury. Neuroreport 10, 645649.
211. Matsunami, M, Kirishi, S, Okui, T, et al. (2011) Chelating luminal zinc mimics hydrogen sulfide-evoked colonic pain in mice: possible involvement of T-type calcium channels. Neuroscience 181, 257264.
212. Nozaki, C, Vergnano, AM, Filliol, D, et al. (2015) Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit. Nat Neurosci 14, 10171022.
213. Kesmati, M & Torabi, M (2014) Interaction between analgesic effect of nano and conventional size of zinc oxide and opioidergic system activity in animal model of acute pain. Basic Clin Neurosci 5, 8087.
214. Fairweather-Tait, SJ, Bao, J, Broadley, MR, et al. (2011) Selenium in human health and disease. Antioxid Redox Signal 4, 13371338.
215. Rayman, MP (2009) Selenoproteins and human health: insights from epidemiological data. Biochim Biophys Acta 1790, 533540.
216. Burk, RF (2002) Selenium, an antioxidant nutrient. Nutr Clin Care 5, 7579.
217. Tinggi, U (2008) Selenium: its role as antioxidant in human health. Environ Health Prev Med 13, 102108.
218. Mattmiller, SA, Bradley, A, Carlson, , et al. (2013) Regulation of inflammation by selenium and selenoproteins: impact on eicosanoid biosynthesis. J Nutr Sci 2, e28.
219. Bleys, J, Navas-Acien, A & Guallar, E (2008) Serum selenium levels and all-cause, cancer, and cardiovascular mortality among US adults. Arch Intern Med 168, 404410.
220. Barros–Neto, JA, Souza-Machado, A & Kraychete, DC (2016) Selenium and zinc status in chronic myofascial pain: serum and erythrocyte concentrations and food intake. PLOS ONE 11, e0164302.
221. Ciubotariu, D, Ghiciuc, CM & Lupusoru, CE (2015) Zinc involvement in opioid addiction and analgesia – should zinc supplementation be recommended for opioid-treated persons? Subst Abuse Treat Prev Policy 10, 29.
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