Vitamin D Deficiency and Pain: Clinical Evidence of Low Levels of Vitamin D and Supplementation in Chronic Pain States

Pain and Therapy

Volumn 4, Issue 1, 2015, Pages 67-87

  Shipton, Elspeth E ^a   Shipton, Edward A ^a  

^a UNIVERSITY OF OTAGO   (New Zealand)

Author keywords

Chronic Pain; Pain Processes; Supplementation; Vitamin D deficiency

Indexed keywords

25 HYDROXYVITAMIN D; COLONY STIMULATING FACTOR 1; INTERLEUKIN 1; NERVE GROWTH FACTOR; TUMOR NECROSIS FACTOR ALPHA; VITAMIN D;

BONE DENSITY; BONE METABOLISM; CALCIUM BLOOD LEVEL; CHRONIC PAIN; CROHN DISEASE; CYSTIC FIBROSIS; DISEASE ASSOCIATION; FIBROMYALGIA; HUMAN; HYPERCALCEMIA; MUSCLE FUNCTION; MUSCLE WEAKNESS; OBESITY; OSTEOPENIA; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RHEUMATIC POLYMYALGIA; RISK FACTOR; SUN EXPOSURE; VITAMIN BLOOD LEVEL; VITAMIN D DEFICIENCY; VITAMIN SUPPLEMENTATION;

EID: 84962898863     PISSN: 21938237     EISSN: 2193651X     Source Type: Journal    
DOI: 10.1007/s40122-015-0036-8     Document Type: Review

References (107)

1. Hollis BW, Wagner CL. Clinical review: the role of the parent compound vitamin D with respect to metabolism and function: Why clinical dose intervals can affect clinical outcomes. J Clin Endocrin Metab. 2013;98(12):4619–28.
2. Mak JC, Klein LA, Finnegan T, Mason RS, Cameron ID. An initial loading-dose vitamin D versus placebo after hip fracture surgery: baseline characteristics of a randomized controlled trial (REVITAHIP). BMC Geriatr. 2014;14:101.
3. Atherton K, Berry DJ, Parsons T, Macfarlane GJ, Power C, Hypponen E. Vitamin D and chronic widespread pain in a white middle-aged British population: evidence from a cross-sectional population survey. Ann Rheum Dis. 2009;68(6):817–22.
4. Straube S, Derry S, Moore RA, McQuay HJ. Vitamin D for the treatment of chronic painful conditions in adults. Cochrane Database Syst Rev. 2010(1):CD007771.
5. McAlindon TE, Felson DT, Zhang Y, Hannan MT, Aliabadi P, Weissman B, et al. Relation of dietary intake and serum levels of vitamin D to progression of osteoarthritis of the knee among participants in the Framingham Study. Ann Intern Med. 1996;125(5):353–9.
6. Straube S, Andrew Moore R, Derry S, McQuay HJ. Vitamin D and chronic pain. Pain. 2009;141(1–2):10–3.
7. Deeb KK, Trump DL, Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer. 2007;7(9):684–700.
8. Brannon PM. Key questions in vitamin D research. Scand J Clin Lab Invest Suppl. 2012;243:154–62.
9. Adams JS, Hewison M. Update in vitamin D. J Clin Endocrin Metab. 2010;95(2):471–8.
10. Zerwekh JE. Blood biomarkers of vitamin D status. Am J Clin Nutr. 2008;87(4):1087S–91S.
11. International Association for the Study of Pain Subcommittee. Classification of chronic pain. Descriptions of chronic pain syndromes and definitions of pain terms. Pain Suppl. 1986;3:S1–226.
12. Seifert F, Maihofner C. Functional and structural imaging of pain-induced neuroplasticity. Curr Opin Anaesthesiol. 2011;24(5):515–23.
13. Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009;10(9):895–926.
14. Flor H, Elbert T, Knecht S, Wienbruch C, Pantev C, Birbaumer N, et al. Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature. 1995;375(6531):482–4.
15. Basbaum A, Bushnel lC, Devor M. Pain: basic mechanisms. In: Pain 2005—an updated review: refresher course syllabus. Seattle: IASP Press; 2005.
16. Woolf CJ, Ma Q. Nociceptors–noxious stimulus detectors. Neuron. 2007;55(3):353–64.
17. Stein C. Opioids, sensory systems and chronic pain. Eur J Pharmacol. 2013;716(1–3):179–87.
18. Moseley GL, Vlaeyen JW. Beyond nociception: the imprecision hypothesis of chronic pain. Pain. 2015;156(1):35–8.
19. Moalem G, Tracey DJ. Immune and inflammatory mechanisms in neuropathic pain. Brain Res Rev. 2006;51(2):240–64.
20. Siddall PJ, Cousins MJ. Persistent pain as a disease entity: implications for clinical management. Anesth Analg. 2004;99(2):510–20.
21. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81.
22. Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc. 2003;78(12):1463–70.
23. Cutolo M, Paolino S, Sulli A, Smith V, Pizzorni C, Seriolo B. Vitamin D, steroid hormones, and autoimmunity. Ann N Y Acad Sci. 2014;1317:39–46.
24. Jesus CA, Feder D, Peres MF. The role of vitamin D in pathophysiology and treatment of fibromyalgia. Curr Pain Headache Rep. 2013;17(8):355.
25. Liao RX, Yu M, Jiang Y, Xia W. Management of osteoporosis with calcitriol in elderly Chinese patients: a systematic review. Clin Interv Aging. 2014;9:515–26.
26. Gloth FM 3rd, Lindsay JM, Zelesnick LB, Greenough WB 3rd. Can vitamin D deficiency produce an unusual pain syndrome? Arch Intern Med. 1991;151(8):1662–4.
27. Simpson RU, Thomas GA, Arnold AJ. Identification of 1,25-dihydroxyvitamin D3 receptors and activities in muscle. J Biol Chem. 1985;260(15):8882–91.
28. Bischoff HA, Stahelin HB, Dick W, Akos R, Knecht M, Salis C, et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res. 2003;18(2):343–51.
29. Hayes M, Yaster M, Haythornthwaite JA, Riekert KA, McMillan KN, White E, et al. Pain is a common problem affecting clinical outcomes in adults with cystic fibrosis. Chest. 2011;140(6):1598–603.
30. West NE, Lechtzin N, Merlo CA, Turowski JB, Davis ME, Ramsay MZ, et al. Appropriate goal level for 25-hydroxyvitamin D in cystic fibrosis. Chest. 2011;140(2):469–74.
31. von Kanel R, Muller-Hartmannsgruber V, Kokinogenis G, Egloff N. Vitamin D and central hypersensitivity in patients with chronic pain. Pain Med. 2014;15(9):1609–18.
32. Bartley J. Could glial activation be a factor in migraine? Med Hypotheses. 2009;72(3):255–7.
33. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152(3 Suppl):S2–15.
34. Zakon HH. The effects of steroid hormones on electrical activity of excitable cells. Trends Neurosci. 1998;21(5):202–7.
35. Wu FS, Gibbs TT, Farb DH. Pregnenolone sulfate: a positive allosteric modulator at the N-methyl-d-aspartate receptor. Mol Pharmacol. 1991;40(3):333–6.
36. Mensah-Nyagan AG, Meyer L, Schaeffer V, Kibaly C, Patte-Mensah C. Evidence for a key role of steroids in the modulation of pain. Psychoneuroendocrinology. 2009;34(Suppl 1):S169–77.
37. Brown J, Bianco JI, McGrath JJ, Eyles DW. 1,25-dihydroxyvitamin D3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons. Neurosci Lett. 2003;343(2):139–43.
38. Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D. New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab. 2002;13(3):100–5.
39. Leung L, Cahill CM. TNF-alpha and neuropathic pain. J Neuroinflammation. 2010;7:27.
40. Marchand F, Perretti M, McMahon SB. Role of the immune system in chronic pain. Nat Rev Neurosci. 2005;6(7):521–32.
41. Prakash S, Mehta NC, Dabhi AS, Lakhani O, Khilari M, Shah ND. The prevalence of headache may be related with the latitude: a possible role of Vitamin D insufficiency? J Headache Pain. 2010;11(4):301–7.
42. Neveu I, Naveilhan P, Jehan F, Baudet C, Wion D, De Luca HF, et al. 1,25-dihydroxyvitamin D3 regulates the synthesis of nerve growth factor in primary cultures of glial cells. Brain Res Mol Brain Res. 1994;24(1–4):70–6.
43. Riaz S, Malcangio M, Miller M, Tomlinson DR. A vitamin D(3) derivative (CB1093) induces nerve growth factor and prevents neurotrophic deficits in streptozotocin-diabetic rats. Diabetologia. 1999;42(11):1308–13.
44. Sanchez B, Relova JL, Gallego R, Ben-Batalla I, Perez-Fernandez R. 1,25-Dihydroxyvitamin D3 administration to 6-hydroxydopamine-lesioned rats increases glial cell line-derived neurotrophic factor and partially restores tyrosine hydroxylase expression in substantia nigra and striatum. J Neurosci Res. 2009;87(3):723–32.
45. Burgess G, Williams D. The discovery and development of analgesics: new mechanisms, new modalities. J Clin Invest. 2010;120(11):3753–9.
46. Woolf CJ. Phenotypic modification of primary sensory neurons: the role of nerve growth factor in the production of persistent pain. Philos Trans R Soc Lond B Biol Sci. 1996;351(1338):441–8.
47. McKelvey L, Shorten GD, O’Keeffe GW. Nerve growth factor-mediated regulation of pain signalling and proposed new intervention strategies in clinical pain management. J Neurochem. 2013;124(3):276–89.
48. Osunkwo I, Ziegler TR, Alvarez J, McCracken C, Cherry K, Osunkwo CE, et al. High dose vitamin D therapy for chronic pain in children and adolescents with sickle cell disease: results of a randomized double blind pilot study. Br J Haematol. 2012;159(2):211–5.
49. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrin Metab. 2011;96(7):1911–30.
50. Sinha A, Cheetham TD, Pearce SH. Prevention and treatment of vitamin D deficiency. Calcif Tissue Int. 2013;92(2):207–15.
51. Glerup H, Mikkelsen K, Poulsen L, Hass E, Overbeck S, Thomsen J, et al. Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. J Intern Med. 2000;247(2):260–8.
52. Zadshir A, Tareen N, Pan D, Norris K, Martins D. The prevalence of hypovitaminosis D among US adults: data from the NHANES III. Ethn Dis. 2005;15(4 Suppl 5):S5-97-101.
53. Allain TJ, Dhesi J. Hypovitaminosis D in older adults. Gerontol. 2003;49(5):273–8.
54. van Schoor NM, Lips P. Worldwide vitamin D status. Best Pract Res Clin Endocrinol Metab. 2011;25(4):671–80.
55. Wagner CL, Greer FR. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics. 2008;122(5):1142–52.
56. Mascitelli L, Goldstein MR, Grant WB. Hypovitaminosis D and pain in cystic fibrosis. Pain Med. 2012;13(5):735–6.
57. Konradsen S, Ag H, Lindberg F, Hexeberg S, Jorde R. Serum 1,25-dihydroxy vitamin D is inversely associated with body mass index. Eur J Nutr. 2008;47(2):87–91.
58. McGill AT, Stewart JM, Lithander FE, Strik CM, Poppitt SD. Relationships of low serum vitamin D3 with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity. Nutr J. 2008;7:4.
59. Parikh SJ, Edelman M, Uwaifo GI, Freedman RJ, Semega-Janneh M, Reynolds J, et al. The relationship between obesity and serum 1,25-dihydroxy vitamin D concentrations in healthy adults. J Clin Endocrin Metab. 2004;89(3):1196–9.
60. Vilarrasa N, Maravall J, Estepa A, Sanchez R, Masdevall C, Navarro MA, et al. Low 25-hydroxyvitamin D concentrations in obese women: their clinical significance and relationship with anthropometric and body composition variables. J Endocrinol Invest. 2007;30(8):653–8.
61. Young KA, Engelman CD, Langefeld CD, Hairston KG, Haffner SM, Bryer-Ash M, et al. Association of plasma vitamin D levels with adiposity in Hispanic and African Americans. J Clin Endocrin Metab. 2009;94(9):3306–13.
62. Brannon PM, Yetley EA, Bailey RL, Picciano MF. Summary of roundtable discussion on vitamin D research needs. Am J Clin Nutr. 2008;88(2):587S–92S.
63. Ritter CS, Brown AJ. Direct suppression of PTH gene expression by the vitamin D prohormones doxercalciferol and calcidiol requires the vitamin D receptor. J Mol Endocrinol. 2011;46(2):63–6.
64. Shinchuk LM, Holick MF. Vitamin D and rehabilitation: improving functional outcomes. Nutr Clin Pract. 2007;22(3):297–304.
65. Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011;86(1):50–60.
66. Souberbielle JC, Courbebaisse M, Cormier C, Pierrot-Deseilligny C, Viard JP, Jean G, et al. When should we measure vitamin D concentration in clinical practice? Scand J Clin Lab Invest Suppl. 2012;243:129–35.
67. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006;84(1):18–28.
68. Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303(18):1815–22.
69. Heaney RP, Armas LA, Shary JR, Bell NH, Binkley N, Hollis BW. 25-Hydroxylation of vitamin D3: relation to circulating vitamin D3 under various input conditions. Am J Clin Nutr. 2008;87(6):1738–42.
70. Hollis BW. Short-term and long-term consequences and concerns regarding valid assessment of vitamin D deficiency: comparison of recent food supplementation and clinical guidance reports. Curr Opin Clin Nutr Metab Care. 2011;14(6):598–604.
71. Rapuri PB, Gallagher JC, Haynatzki G. Effect of vitamins D2 and D3 supplement use on serum 25OHD concentration in elderly women in summer and winter. Calcif Tissue Int. 2004;74(2):150–6.
72. Binkley N, Gemar D, Engelke J, Gangnon R, Ramamurthy R, Krueger D, et al. Evaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly in older adults. J Clin Endocrin Metab. 2011;96(4):981–8.
73. Marshall DT, Savage SJ, Garrett-Mayer E, Keane TE, Hollis BW, Horst RL, et al. Vitamin D3 supplementation at 4000 international units per day for one year results in a decrease of positive cores at repeat biopsy in subjects with low-risk prostate cancer under active surveillance. J Clin Endocrin Metab. 2012;97(7):2315–24.
74. Khazai NB, Judd SE, Jeng L, Wolfenden LL, Stecenko A, Ziegler TR, et al. Treatment and prevention of vitamin D insufficiency in cystic fibrosis patients: comparative 25 efficacy of ergocalciferol, cholecalciferol, and UV light. J Clin Endocrin Metab. 2009;94(6):2037–43.
75. Lips P, Binkley N, Pfeifer M, Recker R, Samanta S, Cohn DA, et al. Once-weekly dose of 8400 IU vitamin D(3) compared with placebo: effects on neuromuscular function and tolerability in older adults with vitamin D insufficiency. J Clin Endocrin Metab. 2010;91(4):985–91.
76. Cipriani C, Romagnoli E, Scillitani A, Chiodini I, Clerico R, Carnevale V, et al. Effect of a single oral dose of 600,000 IU of cholecalciferol on serum calciotropic hormones in young subjects with vitamin D deficiency: a prospective intervention study. J Clin Endocrin Metab. 2010;95(10):4771–7.
77. Malhotra N, Mithal A, Gupta S, Shukla M, Godbole M. Effect of vitamin D supplementation on bone health parameters of healthy young Indian women. Arch Osteoporos. 2009;4(1–2):47–53.
78. Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003;326(7387):469.
79. Vieth R, Chan PC, MacFarlane GD. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am J Clin Nutr. 2001;73(2):288–94.
80. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87(4):1080S–6S.
81. Bergman P, Lindh AU, Bjorkhem-Bergman L, Lindh JD. Vitamin D and respiratory tract infections: a systematic review and meta-analysis of randomized controlled trials. PLoS One. 2013;8(6):e65835.
82. Huang W, Shah S, Long Q, Crankshaw AK, Tangpricha V. Improvement of pain, sleep, and quality of life in chronic pain patients with vitamin D supplementation. Clin J Pain. 2013;29(4):341–7.
83. Holick MF, Biancuzzo RM, Chen TC, Klein EK, Young A, Bibuld D, et al. Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrin Metab. 2008;93(3):677–81.
84. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77(1):204–10.
85. Mocanu V, Stitt PA, Costan AR, Voroniuc O, Zbranca E, Luca V, et al. Long-term effects of giving nursing home residents bread fortified with 125 microg (5000 IU) vitamin D(3) per daily serving. Am J Clin Nutr. 2009;89(4):1132–7.
86. Patel R, Collins D, Bullock S, Swaminathan R, Blake GM, Fogelman I. The effect of season and vitamin D supplementation on bone mineral density in healthy women: a double-masked crossover study. Osteoporos Int. 2001;12(4):319–25.
87. Smith SM, Gardner KK, Locke J, Zwart SR. Vitamin D supplementation during Antarctic winter. Am J Clin Nutr. 2009;89(4):1092–8.
88. Heaney RP. Vitamin D: criteria for safety and efficacy. Nutrition Rev. 2008;66(10 Suppl 2):S178–81.
89. Vieth R. Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults. J Steroid Biochem Mol Biol. 2004;89–90(1–5):575–9.
90. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17(1):1–12.
91. Warner AE, Arnspiger SA. Diffuse musculoskeletal pain is not associated with low vitamin D levels or improved by treatment with vitamin D. J Clin Rheumatol. 2008;14(1):12–6.
92. Schreuder F, Bernsen RM, van der Wouden JC. Vitamin D supplementation for nonspecific musculoskeletal pain in non-Western immigrants: a randomized controlled trial. Ann Fam Med. 2012;10(6):547–55.
93. McAlindon T, LaValley M, Schneider E, Nuite M, Lee JY, Price LL, et al. Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis: a randomized controlled trial. JAMA. 2013;309(2):155–62.
94. Sanghi D, Mishra A, Sharma AC, Singh A, Natu SM, Agarwal S, et al. Does vitamin D improve osteoarthritis of the knee: a randomized controlled pilot trial. Clin Orthop Relat Res. 2013;471(11):3556–62.
95. Rastelli AL, Taylor ME, Gao F, Armamento-Villareal R, Jamalabadi-Majidi S, Napoli N, et al. Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial. Breast Cancer Res Treat. 2011;129(1):107–16.
96. Di Munno O, Beghe F, Favini P, Di Giuseppe P, Pontrandolfo A, Occhipinti G, et al. Prevention of glucocorticoid-induced osteopenia: effect of oral 25-hydroxyvitamin D and calcium. Clin Rheumatol. 1989;8(2):202–7.
97. Wepner F, Scheuer R, Schuetz-Wieser B, Machacek P, Pieler-Bruha E, Cross HS, et al. Effects of vitamin D on patients with fibromyalgia syndrome: a randomized placebo-controlled trial. Pain. 2014;155(2):261–8.
98. Sakalli H, Arslan D, Yucel AE. The effect of oral and parenteral vitamin D supplementation in the elderly: a prospective, double-blinded, randomized, placebo controlled study. Rheumatol Int. 2012;32(8):2279–83.
99. Brohult J, Jonson B. Effects of large doses of calciferol on patients with rheumatoid arthritis. A double-blind clinical trial. Scand J Rheumatol. 1973;2(4):173–6.
100. Yamauchi Y, Tsunematsu T, Konda S, Hoshino T, Itokawa Y, Hoshizaki H. A double blind trial of alfacalcidol on patients with rheumatoid arthritis (RA). Rheumatism. 1989;29(1):11–24.
101. Lee P, Chen R. Vitamin D as an analgesic for patients with type 2 diabetes and neuropathic pain. Arch Intern Med. 2008;168(7):771–2.
102. Iwamoto J, Takeda T, Ichimura S, Matsu K, Uzawa M. Effects of cyclical etidronate with alfacalcidol on lumbar bone mineral density, bone resorption, and back pain in postmenopausal women with osteoporosis. J Orthop Sci. 2003;8(4):532–7.
103. de Torrente de la Jara G, Pecoud A, Favrat B. Musculoskeletal pain in female asylum seekers and hypovitaminosis D3. BMJ. 2004;329(7458):156–7.
104. Spedding S. Vitamin D and depression: a systematic review and meta-analysis comparing studies with and without biological flaws. Nutrients. 2014;6(4):1501–18.
105. Hogberg G, Gustafsson SA, Hallstrom T, Gustafsson T, Klawitter B, Petersson M. Depressed adolescents in a case-series were low in vitamin D and depression was ameliorated by vitamin D supplementation. Acta Paediatr. 2012;101(7):779–83.
106. Basaran S, Guzel R, Coskun-Benlidayi I, Guler-Uysal F. Vitamin D status: effects on quality of life in osteoporosis among Turkish women. Qual Life Res. 2007;16(9):1491–9.
107. Vieth R, Kimball S, Hu A, Walfish PG. Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients. Nutr J. 2004;3:8.