Table of Contents Author Guidelines Submit a Manuscript
Pain Research and Treatment
Volume 2015, Article ID 904967, 12 pages
http://dx.doi.org/10.1155/2015/904967
Review Article

Vitamin D and Pain: Vitamin D and Its Role in the Aetiology and Maintenance of Chronic Pain States and Associated Comorbidities

Department of Anaesthesia, University of Otago, Christchurch, Corner of Riccarton and Hagley Avenues, Christchurch 8042, New Zealand

Received 17 January 2015; Accepted 15 March 2015

Academic Editor: Giustino Varrassi

Copyright © 2015 Edward A. Shipton and Elspeth E. Shipton. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. F. Holick, “Vitamin D deficiency,” The New England Journal of Medicine, vol. 357, no. 3, pp. 266–281, 2007. View at Publisher · View at Google Scholar · View at Scopus
  2. K. K. Deeb, D. L. Trump, and C. S. Johnson, “Vitamin D signalling pathways in cancer: potential for anticancer therapeutics,” Nature Reviews Cancer, vol. 7, no. 9, pp. 684–700, 2007. View at Publisher · View at Google Scholar · View at Scopus
  3. T. D. Thacher and B. L. Clarke, “Vitamin D insufficiency,” Mayo Clinic Proceedings, vol. 86, no. 1, pp. 50–60, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. K. L. Munger, L. I. Levin, B. W. Hollis, N. S. Howard, and A. Ascherio, “Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis,” Journal of the American Medical Association, vol. 296, no. 23, pp. 2832–2838, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. P. M. Brannon, “Key questions in Vitamin D research,” Scandinavian Journal of Clinical and Laboratory Investigation Supplementum, vol. 243, pp. 154–162, 2012. View at Google Scholar
  6. G. A. Plotnikoff and J. M. Quigley, “Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain,” Mayo Clinic Proceedings, vol. 78, no. 12, pp. 1463–1470, 2003. View at Publisher · View at Google Scholar · View at Scopus
  7. M. Cutolo, S. Paolino, A. Sulli, V. Smith, C. Pizzorni, and B. Seriolo, “Vitamin D, steroid hormones, and autoimmunity,” Annals of the New York Academy of Sciences, vol. 1317, no. 1, pp. 39–46, 2014. View at Publisher · View at Google Scholar · View at Scopus
  8. C. A. S. Jesus, D. Feder, and M. F. P. Peres, “The role of vitamin D in pathophysiology and treatment of fibromyalgia,” Current Pain and Headache Reports, vol. 17, no. 8, p. 355, 2013. View at Publisher · View at Google Scholar · View at Scopus
  9. J. S. Adams and M. Hewison, “Update in vitamin D,” The Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 2, pp. 471–478, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. J. Zerwekh, “Blood biomarkers of vitamin D status 1, 2, 3, 4,” The American Journal of Clinical Nutrition, vol. 87, no. 4, pp. 1087S–1091S, 2008. View at Google Scholar
  11. O. A. Gressner, B. Lahme, and A. M. Gressner, “Gc-globulin (vitamin D binding protein) is synthesized and secreted by hepatocytes and internalized by hepatic stellate cells through Ca2+-dependent interaction with the megalin/gp330 receptor,” Clinica Chimica Acta, vol. 390, no. 1-2, pp. 28–37, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. G. J. Atkins, P. H. Anderson, D. M. Findlay et al., “Metabolism of vitamin D3 in human osteoblasts: evidence for autocrine and paracrine activities of 1 alpha, 25-dihydroxyvitamin D3,” Bone, vol. 40, no. 6, pp. 1517–1528, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. T. E. Willnow and A. Nykjaer, “Cellular uptake of steroid carrier proteins—mechanisms and implications,” Molecular and Cellular Endocrinology, vol. 316, no. 1, pp. 93–102, 2010. View at Publisher · View at Google Scholar · View at Scopus
  14. B. W. Hollis and C. L. Wagner, “The role of the parent compound vitamin D with respect to metabolism and function: why clinical dose intervals can affect clinical outcomes,” Journal of Clinical Endocrinology and Metabolism, vol. 98, no. 12, pp. 4619–4628, 2013. View at Publisher · View at Google Scholar · View at Scopus
  15. H. Merskey and N. Bogduk, Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms, IASP Press, Seattle, Wash, USA, 2nd edition, 1994.
  16. A. Basbaum, C. Bushnell, and M. Devor, “Pain: basic mechanisms,” in Pain 2005: An Updated Review: Refresher Course Syllabus, D. Justins, Ed., pp. 3–12, IASP Press, Seattle, Wash, USA, 2005. View at Google Scholar
  17. C. J. Woolf and Q. Ma, “Nociceptors-noxious stimulus detectors,” Neuron, vol. 55, no. 3, pp. 353–364, 2007. View at Publisher · View at Google Scholar · View at Scopus
  18. P. Suchdev, “Pathophysiology of pain,” in Manual of Pain Management, C. Warfield and H. Fausett, Eds., pp. 6–10, Lippincott Williams & Wilkins, Philadelphia, Pa, USA, 2nd edition, 2002. View at Google Scholar
  19. F. Porrec, “Nociceptors, the spinal dorsal horn, and descending modulation,” in Pain 2012: Refresher Courses, 14th World Congress on Pain, I. Tracey, Ed., pp. 3–14, IASP Press, Seattle, DC, USA, 2012. View at Google Scholar
  20. T. W. Vanderah, “Pathophysiology of pain,” The Medical Clinics of North America, vol. 91, no. 1, pp. 1–12, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. International Association for the Study of Pain, “Classification of chronic pain,” Pain, supplement 3, pp. S1–S226, 1986. View at Google Scholar
  22. F. Seifert and C. Maihöfner, “Functional and structural imaging of pain-induced neuroplasticity,” Current Opinion in Anaesthesiology, vol. 24, no. 5, pp. 515–523, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. A. Latremoliere and C. J. Woolf, “Central sensitization: a generator of pain hypersensitivity by central neural plasticity,” Journal of Pain, vol. 10, no. 9, pp. 895–926, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. H. Flor, T. Elbert, S. Knecht et al., “Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation,” Nature, vol. 375, no. 6531, pp. 482–484, 1995. View at Publisher · View at Google Scholar · View at Scopus
  25. P. J. Siddall, “Neuroplasticity and pain: what does it all mean?” Medical Journal of Australia, vol. 198, no. 4, pp. 177–178, 2013. View at Publisher · View at Google Scholar · View at Scopus
  26. C. Stein, “Opioids, sensory systems and chronic pain,” European Journal of Pharmacology, vol. 716, no. 1–3, pp. 179–187, 2013. View at Publisher · View at Google Scholar · View at Scopus
  27. G. Moalem and D. J. Tracey, “Immune and inflammatory mechanisms in neuropathic pain,” Brain Research Reviews, vol. 51, no. 2, pp. 240–264, 2006. View at Publisher · View at Google Scholar
  28. P. J. Siddall and M. J. Cousins, “Persistent pain as a disease entity: implications for clinical management,” Anesthesia and Analgesia, vol. 99, no. 2, pp. 510–520, 2004. View at Google Scholar · View at Scopus
  29. E. A. Shipton, “The transition from acute to chronic post surgical pain,” Anaesthesia and Intensive Care, vol. 39, no. 5, pp. 824–836, 2011. View at Google Scholar · View at Scopus
  30. C. J. Woolf, “Central sensitization: Implications for the diagnosis and treatment of pain,” Pain, vol. 152, no. 3, pp. S2–S15, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. I. Belfer, “Nature and nurture of human pain,” Scientifica, vol. 2013, Article ID 415279, 19 pages, 2013. View at Publisher · View at Google Scholar
  32. F. M. Blyth, L. M. March, A. J. M. Brnabic, L. R. Jorm, M. Williamson, and M. J. Cousins, “Chronic pain in Australia: a prevalence study,” Pain, vol. 89, no. 2-3, pp. 127–134, 2001. View at Publisher · View at Google Scholar · View at Scopus
  33. H. Breivik, B. Collett, V. Ventafridda, R. Cohen, and D. Gallacher, “Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment,” European Journal of Pain, vol. 10, no. 4, pp. 287–333, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. D. Hoy, C. Bain, G. Williams et al., “A systematic review of the global prevalence of low back pain,” Arthritis and Rheumatism, vol. 64, no. 6, pp. 2028–2037, 2012. View at Publisher · View at Google Scholar · View at Scopus
  35. A. Abdulla, N. Adams, M. Bone et al., “Guidance on the management of pain in older people,” Age and Ageing, vol. 42, supplement 1, pp. 1–57, 2013. View at Publisher · View at Google Scholar · View at Scopus
  36. P. M. Grace, M. R. Hutchinson, S. F. Maier, and L. R. Watkins, “Pathological pain and the neuroimmune interface,” Nature Reviews Immunology, vol. 14, no. 4, pp. 217–231, 2014. View at Publisher · View at Google Scholar · View at Scopus
  37. J. M. Teno, S. Weitzen, T. Wetle, and V. Mor, “Persistent pain in nursing home residents,” The Journal of the American Medical Association, vol. 285, no. 16, p. 2081, 2081. View at Google Scholar
  38. Economics A. The High Price of Pain: The Economic Impact of Persistent Pain in Australia, MBF Foundation, 2007.
  39. P. L. Kaza and T. Moulton, “Severe vitamin D deficiency in a patient with sickle cell disease: a case study with literature review,” Journal of Pediatric Hematology/Oncology, vol. 36, no. 4, pp. 293–296, 2014. View at Publisher · View at Google Scholar · View at Scopus
  40. K. Atherton, D. J. Berry, T. Parsons, G. J. Macfarlane, C. Power, and E. Hyppönen, “Vitamin D and chronic widespread pain in a white middle-aged British population: evidence from a cross-sectional population survey,” Annals of the Rheumatic Diseases, vol. 68, no. 6, pp. 817–822, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. S. Straube, S. Derry, R. A. Moore, and H. J. McQuay, “Vitamin D for the treatment of chronic painful conditions in adults,” The Cochrane Database of Systematic Reviews, no. 1, Article ID CD007771, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. J. Bartley, “Prevalence of vitamin D deficiency among patients attending a multidisciplinary tertiary pain clinic,” New Zealand Medical Journal, vol. 121, no. 1286, pp. 57–62, 2008. View at Google Scholar · View at Scopus
  43. M. Z. Erkal, J. Wilde, Y. Bilgin et al., “High prevalence of vitamin D deficiency, secondary hyperparathyroidism and generalized bone pain in Turkish immigrants in Germany: identification of risk factors,” Osteoporosis International, vol. 17, no. 8, pp. 1133–1140, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. P. J. van Veldhuizen, S. A. Taylor, S. Williamson, and B. M. Drees, “Treatment of vitamin D deficiency in patients with metastatic prostate cancer may improve bone pain and muscle strength,” Journal of Urology, vol. 163, no. 1, pp. 187–190, 2000. View at Publisher · View at Google Scholar · View at Scopus
  45. A. Lotfi, A. M. Abdel-Nasser, A. Hamdy, A. A. Omran, and M. A. El-Rehany, “Hypovitaminosis D in female patients with chronic low back pain,” Clinical Rheumatology, vol. 26, no. 11, pp. 1895–1901, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. S. Al Faraj and K. Al Mutairi, “Vitamin d deficiency and chronic low back pain in Saudi Arabia,” Spine, vol. 28, no. 2, pp. 177–179, 2003. View at Publisher · View at Google Scholar · View at Scopus
  47. G. de Torrenté de la Jara, A. Pécoud, and B. Favrat, “Female asylum seekers with musculoskeletal pain: the importance of diagnosis and treatment of hypovitaminosis D,” BioMedical Central Family Practice, vol. 7, article 4, 2006. View at Publisher · View at Google Scholar · View at Scopus
  48. W. Huang, S. Shah, Q. Long, A. K. Crankshaw, and V. Tangpricha, “Improvement of pain, sleep, and quality of life in chronic pain patients with vitamin D supplementation,” Clinical Journal of Pain, vol. 29, no. 4, pp. 341–347, 2013. View at Publisher · View at Google Scholar · View at Scopus
  49. J. Iwamoto, T. Takeda, S. Ichimura, K. Matsu, and M. Uzawa, “Effects of cyclical etidronate with alfacalcidol on lumbar bone mineral density, bone resorption, and back pain in postmenopausal women with osteoporosis,” Journal of Orthopaedic Science, vol. 8, no. 4, pp. 532–537, 2003. View at Publisher · View at Google Scholar · View at Scopus
  50. G. de Torrenté de la Jara, A. Pécoud, and B. Favrat, “Musculoskeletal pain in female asylum seekers and hypovitaminosis D3,” British Medical Journal, vol. 329, no. 7458, pp. 156–157, 2004. View at Publisher · View at Google Scholar · View at Scopus
  51. P. Lee and R. Chen, “Vitamin D as an analgesic for patients with type 2 diabetes and neuropathic pain,” Archives of Internal Medicine, vol. 168, no. 7, pp. 771–772, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. S. Prakash, N. C. Mehta, A. S. Dabhi, O. Lakhani, M. Khilari, and N. D. Shah, “The prevalence of headache may be related with the latitude: a possible role of Vitamin D insufficiency?” The Journal of Headache and Pain, vol. 11, no. 4, pp. 301–307, 2010. View at Publisher · View at Google Scholar · View at Scopus
  53. M. Saps, C. Blank, S. Khan et al., “Seasonal variation in the presentation of abdominal pain,” Journal of Pediatric Gastroenterology and Nutrition, vol. 46, no. 3, pp. 279–284, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. D. D. Mitsikostas, D. Tsaklakidou, N. Athanasiadis, and A. Thomas, “The prevalence of headache in Greece: correlations to latitude and climatological factors,” Headache, vol. 36, no. 3, pp. 168–173, 1996. View at Publisher · View at Google Scholar · View at Scopus
  55. Q. Y. Zeng, R. Chen, Z. Y. Xiao et al., “Low prevalence of knee and back pain in southeast China; the Shantou COPCORD study,” The Journal of Rheumatology, vol. 31, no. 12, pp. 2439–2443, 2004. View at Google Scholar · View at Scopus
  56. H. Glerup, K. Mikkelsen, L. Poulsen et al., “Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited,” Journal of Internal Medicine, vol. 247, no. 2, pp. 260–268, 2000. View at Publisher · View at Google Scholar · View at Scopus
  57. D. S. Arvold, M. J. Odean, M. P. Dornfeld et al., “Corelation of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment: a randomized controlled trial,” Endocrine Practice, vol. 15, no. 3, pp. 203–212, 2009. View at Publisher · View at Google Scholar · View at Scopus
  58. R. C. Oh and J. D. Johnson, “Chest pain and costochondritis associated with vitamin D deficiency: a report of two cases,” Case Reports in Medicine, vol. 2012, Article ID 375730, 3 pages, 2012. View at Publisher · View at Google Scholar
  59. S. Waikakul, “Serum 25-hydroxy-calciferol level and failed back surgery syndrome,” Journal of Orthopaedic Surgery (Hong Kong), vol. 20, no. 1, pp. 18–22, 2012. View at Google Scholar · View at Scopus
  60. B. N. Ames, “Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrient by triage,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 47, pp. 17589–17594, 2006. View at Publisher · View at Google Scholar · View at Scopus
  61. L. L. Ritterhouse, S. R. Crowe, T. B. Niewold et al., “Vitamin D deficiency is associated with an increased autoimmune response in healthy individuals and in patients with systemic lupus erythematosus,” Annals of the Rheumatic Diseases, vol. 70, no. 9, pp. 1569–1574, 2011. View at Publisher · View at Google Scholar · View at Scopus
  62. K. Gopinath and D. Danda, “Supplementation of 1,25 dihydroxy vitamin D3 in patients with treatment naive early rheumatoid arthritis: a randomised controlled trial,” International Journal of Rheumatic Diseases, vol. 14, no. 4, pp. 332–339, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. M. Hayes, M. Yaster, J. A. Haythornthwaite et al., “Pain is a common problem affecting clinical outcomes in adults with cystic fibrosis,” Chest, vol. 140, no. 6, pp. 1598–1603, 2011. View at Publisher · View at Google Scholar · View at Scopus
  64. N. E. West, N. Lechtzin, C. A. Merlo et al., “Appropriate goal level for 25-hydroxyvitamin D in cystic fibrosis,” Chest, vol. 140, no. 2, pp. 469–474, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. T. L. Glover, B. R. Goodin, A. L. Horgas et al., “Vitamin D, race, and experimental pain sensitivity in older adults with knee osteoarthritis,” Arthritis & Rheumatism, vol. 64, no. 12, pp. 3926–3935, 2012. View at Publisher · View at Google Scholar · View at Scopus
  66. G. Högberg, S. A. Gustafsson, T. Hällström, T. Gustafsson, B. Klawitter, and M. Petersson, “Depressed adolescents in a case-series were low in vitamin D and depression was ameliorated by vitamin D supplementation,” Acta Paediatrica, vol. 101, no. 7, pp. 779–783, 2012. View at Publisher · View at Google Scholar · View at Scopus
  67. S. Basaran, R. Guzel, I. Coskun-Benlidayi, and F. Guler-Uysal, “Vitamin D status: effects on quality of life in osteoporosis among Turkish women,” Quality of Life Research, vol. 16, no. 9, pp. 1491–1499, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. R. Vieth, S. Kimball, A. Hu, and P. G. Walfish, “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,” Nutrition Journal, vol. 3, article 8, 2004. View at Publisher · View at Google Scholar · View at Scopus
  69. V. Kunadian, G. A. Ford, B. Bawamia, W. Qiu, and J. E. Manson, “Vitamin D deficiency and coronary artery disease: a review of the evidence,” American Heart Journal, vol. 167, no. 3, pp. 283–291, 2014. View at Publisher · View at Google Scholar · View at Scopus
  70. H. A. Bischoff-Ferrari, D. P. Kiel, B. Dawson-Hughes et al., “Dietary calcium and serum 25-hydroxyvitamin D status in relation to BMD among U.S. adults,” Journal of Bone and Mineral Research, vol. 24, no. 5, pp. 935–942, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. T. Penney, M. Ploughman, M. W. Austin, D. G. Behm, and J. M. Byrne, “Determining the activation of gluteus medius and the validity of the single leg stance test in chronic non-specific low back pain,” Archives of Physical Medicine and Rehabilitation, vol. 95, no. 10, pp. 1969–1976, 2014. View at Publisher · View at Google Scholar
  72. K. H. Cho, J. W. Beom, T. S. Lee, J. H. Lim, T. H. Lee, and J. H. Yuk, “Trunk muscles strength as a risk factor for nonspecific low back pain: a pilot study,” Annals of Rehabilitation Medicine, vol. 38, no. 2, pp. 234–240, 2014. View at Publisher · View at Google Scholar · View at Scopus
  73. H. A. Bischoff, H. B. Stähelin, W. Dick et al., “Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial,” Journal of Bone and Mineral Research, vol. 18, no. 2, pp. 343–351, 2003. View at Publisher · View at Google Scholar · View at Scopus
  74. M. Pfeifer, B. Begerow, and H. W. Minne, “Vitamin D and muscle function,” Osteoporosis International, vol. 13, no. 3, pp. 187–194, 2002. View at Publisher · View at Google Scholar · View at Scopus
  75. R. U. Simpson, G. A. Thomas, and A. J. Arnold, “Identification of 1,25-dihydroxyvitamin: D3 receptors and activities in muscle,” The Journal of Biological Chemistry, vol. 260, no. 15, pp. 8882–8891, 1985. View at Google Scholar · View at Scopus
  76. H. A. Bischoff, M. Borchers, F. Gudat et al., “In situ detection of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue,” The Histochemical Journal, vol. 33, no. 1, pp. 19–24, 2001. View at Publisher · View at Google Scholar · View at Scopus
  77. O. H. Sørensen, B. Lund, B. Saltin et al., “Myopathy in bone loss of ageing: improvement by treatment with 1α-hydroxycholecalciferol and calcium,” Clinical Science, vol. 56, no. 2, pp. 157–161, 1979. View at Google Scholar · View at Scopus
  78. M. Pfeifer, B. Begerow, H. W. Minne et al., “Vitamin D status, trunk muscle strength, body sway, falls, and fractures among 237 postmenopausal women with osteoporosis,” Experimental and Clinical Endocrinology & Diabetes, vol. 109, no. 2, pp. 87–92, 2001. View at Publisher · View at Google Scholar · View at Scopus
  79. K. E. Broe, T. C. Chen, J. Weinberg, H. A. Bischoff-Ferrari, M. F. Holick, and D. P. Kiel, “A higher dose of vitamin D reduces the risk of falls in nursing home residents: a randomized, multiple-dose study,” Journal of the American Geriatrics Society, vol. 55, no. 2, pp. 234–239, 2007. View at Publisher · View at Google Scholar · View at Scopus
  80. L. Flicker, K. Mead, C. Nowson et al., “Risk factors for falls in older women in residential care in Australia,” Journal of Bone and Mineral Research, vol. 16, supplement 1, p. S170, 2001. View at Google Scholar
  81. P. Geusens, C. Vandevyver, J. Vanhoof, J.-J. Cassiman, S. Boonen, and J. Raus, “Quadriceps and grip strength are related to vitamin D receptor genotype in elderly nonobese women,” Journal of Bone and Mineral Research, vol. 12, no. 12, pp. 2082–2088, 1997. View at Publisher · View at Google Scholar · View at Scopus
  82. L. M. Shinchuk and M. F. Holick, “Vitamin D and rehabilitation: improving functional outcomes,” Nutrition in Clinical Practice, vol. 22, no. 3, pp. 297–304, 2007. View at Publisher · View at Google Scholar · View at Scopus
  83. D. A. Fernandes de Abreu, D. Eyles, and F. Féron, “Vitamin D, a neuro-immunomodulator: implications for neurodegenerative and autoimmune diseases,” Psychoneuroendocrinology, vol. 34, supplement 1, pp. S265–S277, 2009. View at Publisher · View at Google Scholar · View at Scopus
  84. A. V. Kalueff and P. Tuohimaa, “Neurosteroid hormone vitamin D and its utility in clinical nutrition,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 10, no. 1, pp. 12–19, 2007. View at Publisher · View at Google Scholar · View at Scopus
  85. H. H. Zakon, “The effects of steroid hormones on electrical activity of excitable cells,” Trends in Neurosciences, vol. 21, no. 5, pp. 202–207, 1998. View at Publisher · View at Google Scholar · View at Scopus
  86. F.-S. Wu, T. T. Gibbs, and D. H. Farb, “Pregnenolone sulfate: a positive allosteric modulator at the N-methyl-D-aspartate receptor,” Molecular Pharmacology, vol. 40, no. 3, pp. 333–336, 1991. View at Google Scholar · View at Scopus
  87. A. G. Mensah-Nyagan, L. Meyer, V. Schaeffer, C. Kibaly, and C. Patte-Mensah, “Evidence for a key role of steroids in the modulation of pain,” Psychoneuroendocrinology, vol. 34, supplement 1, pp. S169–S177, 2009. View at Publisher · View at Google Scholar · View at Scopus
  88. C. Carlberg and M. J. Campbell, “Vitamin D receptor signaling mechanisms: integrated actions of a well-defined transcription factor,” Steroids, vol. 78, no. 2, pp. 127–136, 2013. View at Publisher · View at Google Scholar · View at Scopus
  89. I. Neveu, P. Naveilhan, F. Jehan et al., “1,25-dihydroxyvitamin D3 regulates the synthesis of nerve growth factor in primary cultures of glial cells,” Molecular Brain Research, vol. 24, no. 1–4, pp. 70–76, 1994. View at Publisher · View at Google Scholar · View at Scopus
  90. J. Brown, J. I. Bianco, J. J. McGrath, and D. W. Eyles, “1,25-Dihydroxyvitamin D3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons,” Neuroscience Letters, vol. 343, no. 2, pp. 139–143, 2003. View at Publisher · View at Google Scholar · View at Scopus
  91. S. Riaz, M. Malcangio, M. Miller, and D. R. Tomlinson, “A vitamin D3 derivative (CB1093) induces nerve growth factor and prevents neurotrophic deficits in streptozotocin-diabetic rats,” Diabetologia, vol. 42, no. 11, pp. 1308–1313, 1999. View at Publisher · View at Google Scholar · View at Scopus
  92. E. Garcion, N. Wion-Barbot, C. N. Montero-Menei, F. Berger, and D. Wion, “New clues about vitamin D functions in the nervous system,” Trends in Endocrinology and Metabolism, vol. 13, no. 3, pp. 100–105, 2002. View at Publisher · View at Google Scholar · View at Scopus
  93. F. Marchand, M. Perretti, and S. B. McMahon, “Role of the immune system in chronic pain,” Nature Reviews Neuroscience, vol. 6, no. 7, pp. 521–532, 2005. View at Publisher · View at Google Scholar · View at Scopus
  94. L. McKelvey, G. D. Shorten, and G. W. O'Keeffe, “Nerve growth factor-mediated regulation of pain signalling and proposed new intervention strategies in clinical pain management,” Journal of Neurochemistry, vol. 124, no. 3, pp. 276–289, 2013. View at Publisher · View at Google Scholar · View at Scopus
  95. C. J. Woolf, “Phenotypic modification of primary sensory neurons: the role of nerve growth factor in the production of persistent pain,” Philosophical Transactions of the Royal Society B: Biological Sciences, vol. 351, no. 1338, pp. 441–448, 1996. View at Publisher · View at Google Scholar · View at Scopus
  96. L. R. Harms, T. H. J. Burne, D. W. Eyles, and J. J. McGrath, “Vitamin D and the brain,” Best Practice & Research: Clinical Endocrinology & Metabolism, vol. 25, no. 4, pp. 657–669, 2011. View at Publisher · View at Google Scholar · View at Scopus
  97. L. D. Brewer, V. Thibault, K.-C. Chen, M. C. Langub, P. W. Landfield, and N. M. Porter, “Vitamin D hormone confers neuroprotection in parallel with downregulation of L-type calcium channel expression in hippocampal neurons,” Journal of Neuroscience, vol. 21, no. 1, pp. 98–108, 2001. View at Google Scholar · View at Scopus
  98. S. J. Kiraly, M. A. Kiraly, R. D. Hawe, and N. Makhani, “Vitamin D as a neuroactive substance: review,” TheScientificWorldJournal, vol. 6, pp. 125–139, 2006. View at Publisher · View at Google Scholar · View at Scopus
  99. R. S. Griffin, M. Costigan, G. J. Brenner et al., “Complement induction in spinal cord microglia results in anaphylatoxin C5a-mediated pain hypersensitivity,” Journal of Neuroscience, vol. 27, no. 32, pp. 8699–8708, 2007. View at Publisher · View at Google Scholar · View at Scopus
  100. M. Tsuda, K. Inoue, and M. W. Salter, “Neuropathic pain and spinal microglia: a big problem from molecules in ‘small’ glia,” Trends in Neurosciences, vol. 28, no. 2, pp. 101–107, 2005. View at Publisher · View at Google Scholar · View at Scopus
  101. M. Hewison, “Vitamin D and the immune system: new perspectives on an old theme,” Endocrinology and Metabolism Clinics of North America, vol. 39, no. 2, pp. 365–379, 2010. View at Publisher · View at Google Scholar · View at Scopus
  102. D. Feldman, A. Krishnan, J. Moreno, S. Swami, D. M. Peehl, and S. Srinivas, “Vitamin D inhibition of the prostaglandin pathway as therapy for prostate cancer,” Nutrition Reviews, vol. 65, no. 8, part 2, pp. S113–S115, 2007. View at Publisher · View at Google Scholar · View at Scopus
  103. J. D. Richardson and M. R. Vasko, “Cellular mechanisms of neurogenic inflammation,” The Journal of Pharmacology and Experimental Therapeutics, vol. 302, no. 3, pp. 839–845, 2002. View at Publisher · View at Google Scholar · View at Scopus
  104. J. J. Letterio and A. B. Roberts, “Regulation of immune responses by TGF-beta,” Annual Review of Immunology, vol. 16, pp. 137–161, 1998. View at Publisher · View at Google Scholar · View at Scopus
  105. L. Leung and C. M. Cahill, “TNF-α and neuropathic pain—a review,” Journal of Neuroinflammation, vol. 7, article 27, 2010. View at Publisher · View at Google Scholar · View at Scopus
  106. H. F. Deluca and M. T. Cantorna, “Vitamin D: its role and uses in immunology,” The FASEB Journal, vol. 15, no. 14, pp. 2579–2585, 2001. View at Publisher · View at Google Scholar · View at Scopus
  107. Y. Cury, G. Picolo, V. P. Gutierrez, and S. H. Ferreira, “Pain and analgesia: the dual effect of nitric oxide in the nociceptive system,” Nitric Oxide, vol. 25, no. 3, pp. 243–254, 2011. View at Publisher · View at Google Scholar · View at Scopus
  108. E. Garcion, L. Sindji, G. Leblondel, P. Brachet, and F. Darcy, “1, 25-dihydroxyvitamin D3 regulates the synthesis of gamma-glutamyl transpeptidase and glutathione levels in rat primary astrocytes,” Journal of Neurochemistry, vol. 73, no. 2, pp. 859–866, 1999. View at Publisher · View at Google Scholar · View at Scopus
  109. K. Takahashi, Y. Nakayama, H. Horiuchi et al., “Human neutrophils express messenger RNA of vitamin D receptor and respond to 1alpha,25-dihydroxyvitamin D3,” Immunopharmacology and Immunotoxicology, vol. 24, no. 3, pp. 335–347, 2002. View at Publisher · View at Google Scholar · View at Scopus
  110. N. M. Perkins and D. J. Tracey, “Hyperalgesia due to nerve injury: role of neutrophils,” Neuroscience, vol. 101, no. 3, pp. 745–757, 2000. View at Publisher · View at Google Scholar · View at Scopus
  111. J. Lemire, “1,25-dihydroxyvitamin D3—a hormone with immunomodulatory properties,” Zeitschrift für Rheumatologie, vol. 59, supplement 1, pp. 24–27, 2000. View at Publisher · View at Google Scholar · View at Scopus
  112. D. W. Eyles, S. Smith, R. Kinobe, M. Hewison, and J. J. McGrath, “Distribution of the vitamin D receptor and 1α-hydroxylase in human brain,” Journal of Chemical Neuroanatomy, vol. 29, no. 1, pp. 21–30, 2005. View at Publisher · View at Google Scholar · View at Scopus
  113. G. F. Jirikowski, U. W. Kauntzer, A. E. E. Dief, and J. D. Caldwell, “Distribution of vitamin D binding protein expressing neurons in the rat hypothalamus,” Histochemistry and Cell Biology, vol. 131, no. 3, pp. 365–370, 2009. View at Publisher · View at Google Scholar · View at Scopus
  114. R. E. S. Anglin, Z. Samaan, and S. D. Walter, “Vitamin D deficiency and depression in adults: systematic review and meta-analysis,” British Journal of Psychiatry, vol. 202, no. 2, pp. 100–107, 2013. View at Publisher · View at Google Scholar · View at Scopus
  115. S. C. Gominak and W. E. Stumpf, “The world epidemic of sleep disorders is linked to vitamin D deficiency,” Medical Hypotheses, vol. 79, no. 2, pp. 132–135, 2012. View at Publisher · View at Google Scholar · View at Scopus
  116. F. Baeke, T. Takiishi, H. Korf, C. Gysemans, and C. Mathieu, “Vitamin D: modulator of the immune system,” Current Opinion in Pharmacology, vol. 10, no. 4, pp. 482–496, 2010. View at Publisher · View at Google Scholar · View at Scopus
  117. L. Imeri and M. R. Opp, “How (and why) the immune system makes us sleep,” Nature Reviews Neuroscience, vol. 10, no. 3, pp. 199–210, 2009. View at Publisher · View at Google Scholar · View at Scopus
  118. L. Clevenger, A. Schrepf, D. Christensen et al., “Sleep disturbance, cytokines, and fatigue in women with ovarian cancer,” Brain, Behavior, and Immunity, vol. 26, no. 7, pp. 1037–1044, 2012. View at Publisher · View at Google Scholar · View at Scopus
  119. M. R. Opp, “Cytokines and sleep,” Sleep Medicine Reviews, vol. 9, no. 5, pp. 355–364, 2005. View at Publisher · View at Google Scholar · View at Scopus
  120. M. Opp, J. Born, and M. Irwin, “Sleep and the immune system,” in Psychoneuroimmunology, R. Ader, Ed., pp. 579–618, Elsevier Academic Press, Burlington, Mass, USA, 2007. View at Google Scholar
  121. J. M. Krueger, F. J. Obál, J. Fang, T. Kubota, and P. Taishi, “The role of cytokines in physiological sleep regulation,” Annals of the New York Academy of Sciences, vol. 933, pp. 211–221, 2001. View at Google Scholar · View at Scopus
  122. M. Haack, E. Sanchez, and J. M. Mullington, “Elevated inflammatory markers in response to prolonged sleep restriction are associated with increased pain experience in healthy volunteers,” Sleep, vol. 30, no. 9, pp. 1145–1152, 2007. View at Google Scholar · View at Scopus
  123. D. E. McCarty, A. Reddy, Q. Keigley, P. Y. Kim, and A. A. Marino, “Vitamin D, race, and excessive daytime sleepiness,” Journal of Clinical Sleep Medicine, vol. 8, no. 6, pp. 693–697, 2012. View at Publisher · View at Google Scholar · View at Scopus
  124. K. Chopra and V. Arora, “An intricate relationship between pain and depression: clinical correlates, coactivation factors and therapeutic targets,” Expert Opinion on Therapeutic Targets, vol. 18, no. 2, pp. 159–176, 2014. View at Publisher · View at Google Scholar · View at Scopus
  125. M. I. Maes, “Evidence for an immune response in major depression: a review and hypothesis,” Progress in Neuro-psychopharmacology and Biological Psychiatry, vol. 19, no. 1, pp. 11–38, 1995. View at Publisher · View at Google Scholar · View at Scopus
  126. G. J. Summer, E. A. Romero-Sandoval, O. Bogen, O. A. Dina, S. G. Khasar, and J. D. Levine, “Proinflammatory cytokines mediating burn-injury pain,” Pain, vol. 135, no. 1-2, pp. 98–107, 2008. View at Publisher · View at Google Scholar · View at Scopus
  127. N. Üçeyler, T. Eberle, R. Rolke, F. Birklein, and C. Sommer, “Differential expression patterns of cytokines in complex regional pain syndrome,” Pain, vol. 132, no. 1-2, pp. 195–205, 2007. View at Publisher · View at Google Scholar · View at Scopus
  128. C. L. Raison, L. Capuron, and A. H. Miller, “Cytokines sing the blues: Inflammation and the pathogenesis of depression,” Trends in Immunology, vol. 27, no. 1, pp. 24–31, 2006. View at Publisher · View at Google Scholar · View at Scopus
  129. Y. Dowlati, N. Herrmann, W. Swardfager et al., “A meta-analysis of cytokines in major depression,” Biological Psychiatry, vol. 67, no. 5, pp. 446–457, 2010. View at Publisher · View at Google Scholar · View at Scopus
  130. I. J. Russell, H. Vaeroy, M. Javors, and F. Nyberg, “Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis,” Arthritis and Rheumatism, vol. 35, no. 5, pp. 550–556, 1992. View at Publisher · View at Google Scholar · View at Scopus
  131. J. J. Mann and K. M. Malone, “Cerebrospinal fluid amines and higher-lethality suicide attempts in depressed inpatients,” Biological Psychiatry, vol. 41, no. 2, pp. 162–171, 1997. View at Publisher · View at Google Scholar · View at Scopus
  132. L. C. Campbell, D. J. Clauw, and F. J. Keefe, “Persistent pain and depression: a biopsychosocial perspective,” Biological Psychiatry, vol. 54, no. 3, pp. 399–409, 2003. View at Publisher · View at Google Scholar · View at Scopus
  133. A. J. Dunn, “Effects of cytokines and infections on brain neurochemistry,” Clinical Neuroscience Research, vol. 6, no. 1-2, pp. 52–68, 2006. View at Publisher · View at Google Scholar · View at Scopus
  134. D. Brambilla, S. Franciosi, M. R. Opp, and L. Imeri, “Interleukin-1 inhibits firing of serotonergic neurons in the dorsal raphe nucleus and enhances GABAergic inhibitory post-synaptic potentials,” European Journal of Neuroscience, vol. 26, no. 7, pp. 1862–1869, 2007. View at Publisher · View at Google Scholar · View at Scopus
  135. A. Ellis and D. L. H. Bennett, “Neuroinflammation and the generation of neuropathic pain,” British Journal of Anaesthesia, vol. 111, no. 1, pp. 26–37, 2013. View at Publisher · View at Google Scholar · View at Scopus
  136. P. H. Finan, B. R. Goodin, and M. T. Smith, “The association of sleep and pain: an update and a path forward,” Journal of Pain, vol. 14, no. 12, pp. 1539–1552, 2013. View at Publisher · View at Google Scholar · View at Scopus
  137. S. González, D. Moreno-Delgado, E. Moreno et al., “Circadian-related heteromerization of adrenergic and dopamine D4 receptors modulates melatonin synthesis and release in the pineal gland,” PLoS Biology, vol. 10, no. 6, Article ID e1001347, 2012. View at Publisher · View at Google Scholar · View at Scopus
  138. C. A. Naranjo, L. K. Tremblay, and U. E. Busto, “The role of the brain reward system in depression,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 25, no. 4, pp. 781–823, 2001. View at Publisher · View at Google Scholar · View at Scopus
  139. P. B. Wood, “Role of central dopamine in pain and analgesia,” Expert Review of Neurotherapeutics, vol. 8, no. 5, pp. 781–797, 2008. View at Publisher · View at Google Scholar · View at Scopus
  140. P. B. Wood, “Stress and dopamine: implications for the pathophysiology of chronic widespread pain,” Medical Hypotheses, vol. 62, no. 3, pp. 420–424, 2004. View at Publisher · View at Google Scholar · View at Scopus
  141. H. Foo and P. Mason, “Brainstem modulation of pain during sleep and waking,” Sleep Medicine Reviews, vol. 7, no. 2, pp. 145–154, 2003. View at Publisher · View at Google Scholar · View at Scopus
  142. D. C. Nascimento, M. L. Andersen, D. C. Hipólide, J. N. Nobrega, and S. Tufik, “Pain hypersensitivity induced by paradoxical sleep deprivation is not due to altered binding to brain μ-opioid receptors,” Behavioural Brain Research, vol. 178, no. 2, pp. 216–220, 2007. View at Publisher · View at Google Scholar · View at Scopus
  143. O. E. Ukponmwan, J. Rupreht, and M. R. Dzoljic, “REM sleep deprivation decreases the antinociceptive property of enkephalinase-inhibition, morphine and cold-water-swim,” General Pharmacology, vol. 15, no. 3, pp. 255–258, 1984. View at Publisher · View at Google Scholar · View at Scopus
  144. H. A. Baghdoyan, “Hyperalgesia induced by REM sleep loss: a phenomenon in search of a mechanism,” Sleep, vol. 29, no. 2, pp. 137–139, 2006. View at Google Scholar · View at Scopus
  145. A. M. Kshatri, H. A. Baghdoyan, and R. Lydic, “Cholinomimetics, but not morphine, increase antinociceptive behavior from pontine reticular regions regulating rapid-eye-movement sleep,” Sleep, vol. 21, no. 7, pp. 677–685, 1998. View at Google Scholar · View at Scopus
  146. P. L. Delgado, “Depression: the case for a monoamine deficiency,” The Journal of Clinical Psychiatry, vol. 61, no. 6, pp. 7–11, 2000. View at Publisher · View at Google Scholar · View at Scopus
  147. H. L. Fields and A. I. Basbaum, “Central nervous system mechanisms of pain modulation,” in Textbook of Pain, P. Wall and R. Melzack, Eds., pp. 243–257, Churchill Livingstone, New York, NY, USA, 1994. View at Google Scholar
  148. J. Levine and Y. Taiwo, “Inflammatory pain,” in Textbook of Pain, P. Wall and R. Melzack, Eds., pp. 45–56, Churchill Livingstone, New York, NY, USA, 1994. View at Google Scholar
  149. P. M. Dougherty and W. D. Willis, “Enhanced responses of spinothalamic tract neurons to excitatory amino acids accompany capsaicin-induced sensitization in the monkey,” Journal of Neuroscience, vol. 12, no. 3, pp. 883–894, 1992. View at Google Scholar · View at Scopus
  150. D. J. Claliw, “The pathogenesis of chronic pain and fatigue syndromes, with special reference to fibromyalgia,” Medical Hypotheses, vol. 44, no. 5, pp. 369–378, 1995. View at Publisher · View at Google Scholar · View at Scopus
  151. R. Dantzer, J. C. O'Connor, G. G. Freund, R. W. Johnson, and K. W. Kelley, “From inflammation to sickness and depression: when the immune system subjugates the brain,” Nature Reviews. Neuroscience, vol. 9, no. 1, pp. 46–56, 2008. View at Publisher · View at Google Scholar · View at Scopus
  152. J. W. Kasckow, D. Baker, and T. D. Geracioti Jr., “Corticotropin-releasing hormone in depression and post-traumatic stress disorder,” Peptides, vol. 22, no. 5, pp. 845–851, 2001. View at Publisher · View at Google Scholar · View at Scopus
  153. M. Schäfer, S. A. Mousa, Q. Zhang, L. Carter, and C. Stein, “Expression of corticotropin-releasing factor in inflamed tissue is required for intrinsic peripheral opioid analgesia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 12, pp. 6096–6100, 1996. View at Publisher · View at Google Scholar · View at Scopus