Neurology, Neuropsychiatry, Psychosomatics

Advanced search

Nociception: the roles of vitamin D

Full Text:


Objective: to carry out a systematic computer-assisted analysis of scientific literature on on the relationships between the effects of vitamin and nociception (including the impact of vitamin D deficiency on the development of pain syndrome.

Material and methods. For the query “(pain OR nociception) AND (vitamin D OR cholecalciferol OR VITD OR CALCITRIOL OR HYDROXYVITAMIN OR DIHYDROXYVITAMIN OR ALPHACALCIDOL)", 2318 references, including 77 references on alpha-calcidol, were found in the biomedical publications database PubMed. The computer-assisted analysis of this array of publications was carried out using the current big data analysis methods developed within the topological and metric approaches to recognition/classification problems.

Result and discussion. A systematic computer-assisted text analysis of 2318 studies on the relationships between nociception and vitamin D showed that the analgesic effects of the vitamin are by anti-inflammatory action and the regulation of serotonergic, dopaminergic, and opioidergic neurotransmission. The lower blood levels of the major vitamin D metabolite 25 (OH)D is a risk factor for decreased pain threshold in myalgia, fibromyalgia, arthralgia, dorsalgia, and a number of neuralgias.

Conclusion. In patients with impaired renal conversion of active vitamin D metabolites (especially in the elderly), the efficacy of cholecalciferol-based drugs is reduced, which makes it necessary to use the active forms of vitamin D.

About the Authors

O. A. Gromova
Federal Research Center for Informatics and Management, Russian Academy of Sciences; M.V. Lomonosov Moscow State University
Russian Federation

Olga Alekseevna Gromova

Institute of Pharmacoinformatics
44, Vavilov St., Build. 2, Moscow 119333 

Center for Big Data Storage and Analysis, National Center for Digital Economy
1, Leninskie Gory, Moscow 119234 

I. Yu. Torshin
Federal Research Center for Informatics and Management, Russian Academy of Sciences; M.V. Lomonosov Moscow State University
Russian Federation

Institute of Pharmacoinformatics
44, Vavilov St., Build. 2, Moscow 119333 

Center for Big Data Storage and Analysis, National Center for Digital Economy
1, Leninskie Gory, Moscow 119234 

M. V. Putilina
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation
1, Ostrovityanov St., Moscow 117997

I. S. Sardaryan
Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia
Russian Federation
2, Litovskaya St., Saint Petersburg 194100

L. E. Fedotova
Ivanovo State Medical Academy, Ministry of Health of Russia
Russian Federation

8, Sheremetesky Prospect, Ivanovo 153012

O. A. Limanova
Ivanovo State Medical Academy, Ministry of Health of Russia
Russian Federation
8, Sheremetesky Prospect, Ivanovo 153012


1. Gromova OA, Torshin IYu, Gusev EI. Synergistic neuroprotective effects of thiamine, pyridoxine and cyanocobalamin on the level of human proteome. Farmakokinetika i farmakodinamika = Pharmacokinetics and Pharmacodynamics. 2017;(1):40-51 In Russ.).

2. Gromova OA, Torshin IYu, Putilina MV, et al. About the mechanisms of synergistic action of tolperisone, meloxicam and B vitamins in the treatment of peripheral pain syndromes. Meditsinskiy Sovet. 2020;(8):54-64. doi: 10.21518/2079-701X-2020-8-54-64 (In Russ.).

3. Crawford C, Boyd C, Paat CF, et al. Dietary Ingredients as an Alternative Approach for Mitigating Chronic Musculoskeletal Pain: Evidence-Based Recommendations for Practice and Research in the Military. Pain Med. 2019 Jun 1;20(6):1236-47. doi: 10.1093/pm/pnz040

4. Gromova OA, Torshin IYu. Vitamin D – smena paradigmy [Vitamin D – a paradigm shift]. Moscow: GEOTAR-Media; 2017. 568 p. ISBN 978-5-9704-4058-2 (In Russ.).

5. Gromova OA, Torshin IYu, Gilel's AV, Tomilova IK. Effects of inclusion of alfacalcidol in complex rehabilitation programs for patients with age-related facial ptosis. Meditsinskiy Sovet. 2020;(21):14-24 (In Russ.).

6. Torshin IYu, Rudakov KV. Combinatorial analysis of the solvability properties of the problems of recognition and completeness of algorithmic models. Part 2: Metric approach within the framework of the theory of classification of feature values. Pattern Recognit Image Anal. 2017 Apr;27:184-99. doi: 10.1134/S1054661817020110

7. Torshin IYu, Rudakov KV. On the theoretical basis of metric analysis of poorly formalized problems of recognition and classification. Pattern Recognit Image Anal. 2015 Oct;25:577-87. doi: 10.1134/S1054661815040252

8. Torshin IYu, Rudakov KV. On metric spaces arising during formalization of problems of recognition and classification. Part 2: Density properties. Pattern Recognit. Image Anal. 2016 Jul;26(3):483-96. doi: 10.1134/S1054661816030202

9. Banafshe HR, Khoshnoud MJ, Abed A, et al. Vitamin D supplementation attenuates the behavioral scores of neuropathic pain in rats. Nutr Neurosci. 2019 Oct;22(10):700-5. doi: 10.1080/1028415X.2018.1435485. Epub 2018 Feb 12.

10. Helde-Frankling M, Bjorkhem-Bergman L. Vitamin D in Pain Management. Int J Mol Sci. 2017 Oct 18;18(10):2170. doi: 10.3390/ijms18102170

11. Liu Y, Peng W, Li Y, et al. Vitamin D Deficiency Harms Patients with Coronary Heart Disease by Enhancing Inflammation. Med Sci Monit. 2018 Dec 24;24:9376-84. doi: 10.12659/MSM.911615

12. Poisbeau P, Aouad M, Gazzo G, et al. Cholecalciferol (Vitamin D3) Reduces Rat Neuropathic Pain by Modulating Opioid Signaling. Mol Neurobiol. 2019 Oct;56(10):7208-21. doi: 10.1007/s12035-0191582-6. Epub 2019 Apr 18.

13. Guida F, Boccella S, Belardo C, et al. Altered gut microbiota and endocannabinoid system tone in vitamin D deficiency-mediated chronic pain. Brain Behav Immun. 2020 Mar;85:128-41. doi: 10.1016/j.bbi.2019.04.006. Epub 2019 Apr 3.

14. Cass WA, Smith MP, Peters LE. Calcitriol protects against the dopamine- and serotonindepleting effects of neurotoxic doses of methamphetamine. Ann N Y Acad Sci. 2006 Aug;1074:261-71. doi: 10.1196/annals.1369.023

15. Wood PB. Role of central dopamine in pain and analgesia. Expert Rev Neurother. 2008 May;8(5):781-97. doi: 10.1586/14737175.8.5.781

16. De Oliveira DL, Hirotsu C, Tufik S, Andersen ML. The interfaces between vitamin D, sleep and pain. J Endocrinol. 2017 Jul;234(1):R23-R36. doi: 10.1530/JOE-16-0514. Epub 2017 May 23.

17. Cidem M, Karacan I, Beytemur O, Kara S. Prevalence and risk factors for vitamin D deficiency in patients with widespread musculoskeletal pain. Turk J Med Sci. 2017 Jun 12;47(3):728-31. doi: 10.3906/sag-1508-30

18. Babaei M, Esmaeili Jadidi M, Heidari B, Gholinia H. Vitamin D deficiency is associated with tibial bone pain and tenderness. A possible contributive role. Int J Rheum Dis. 2018 Apr;21(4):788-95. doi: 10.1111/1756-185X.13253. Epub 2018 Jan 5.

19. Makrani AH, Afshari M, Ghajar M, et al. Vitamin D and fibromyalgia: a meta-analysis. Korean J Pain. 2017 Oct;30(4):250-7. doi: 10.3344/kjp.2017.30.4.250. Epub 2017 Sep 29.

20. Wu Z, Malihi Z, Stewart AW, et al. The association between vitamin D concentration and pain: a systematic review and metaanalysis. Pub Health Nutr. 2018 Aug;21(11):2022-37. doi: 10.1017/S1368980018000551. Epub 2018 Mar 21.

21. Park CY. Vitamin D in the Prevention and Treatment of Osteoarthritis: From Clinical Interventions to Cellular Evidence. Nutrients. 2019 Jan 22;11(2):243. doi: 10.3390/nu11020243

22. Zheng S, Jin X, Cicuttini F, et al. Maintaining Vitamin D Sufficiency Is Associated with Improved Structural and Symptomatic Outcomes in Knee Osteoarthritis. Am J Med. 2017 Oct;130(10):1211-8. doi: 10.1016/j.amjmed.2017.04.038. Epub 2017 May 24.

23. Yesil H, Sungur U, Akdeniz S, et al. Association between serum vitamin D levels and neuropathic pain in rheumatoid arthritis patients: A cross-sectional study. Int J Rheum Dis. 2018 Feb;21(2):431-9. doi: 10.1111/1756-185X.13160. Epub 2017 Aug 31.

24. Vaishya R, Vijay V, Lama P, Agarwal A. Does vitamin D deficiency influence the incidence and progression of knee osteoarthritis? A literature review. J Clin Orthop Trauma. 2019 Jan-Feb;10(1):9-15. doi: 10.1016/j.jcot.2018.05.012. Epub 2018 May 20.

25. Demiryurek BE, Gundogdu AA. The effect of vitamin D levels on pain in carpal tunnel syndrome. Orthop Traumatol Surg Res. 2017 Oct;103(6):919-22. doi: 10.1016/j.otsr.2017.05.003. Epub 2017 May 25.

26. Nageeb RS, Shehta N, Nageeb GS, Omran AA. Body mass index and vitamin D level in carpal tunnel syndrome patients. Egypt J Neurol Psychiatr Neurosurg. 2018;54(1):14. doi: 10.1186/s41983-018-0009-z. Epub 2018 May 3.

27. Gokcek E, Kaydu A. Assessment of Relationship between Vitamin D Deficiency and Pain Severity in Patients with Low Back Pain: A Retrospective, Observational Study. Anesth Essays Res. 2018 Jul-Sep;12(3):680-4. doi: 10.4103/aer.AER_96_18

28. Bansal D, Boya CS, Vatte R, Ghai B. High Prevalence of Hypovitaminosis D in Patients with Low Back Pain: Evidence from Meta-Analysis. Pain Physician. 2018 Jul;21(4):E389-E399. doi: 10.36076/ppj.2018.4.E389

29. Raslan E, Soliman SSA, Nour ZA, et al. Association of Vitamin D Deficiency with Chronic Stable Angina: A Case Control Study. High Blood Press Cardiovasc Prev. 2019 Feb;26(1):77-80. doi: 10.1007/s40292-0180295-7. Epub 2018 Dec 26.

30. Sharma N, Cooper R, Kuh D, Shah I. Associations of statin use with motor performance and myalgia may be modified by 25hydroxyvitamin D: findings from a British birth cohort. Sci Rep. 2017 Jul 26;7(1):6578. doi: 10.1038/s41598-017-06019-z

31. Pennisi M, Di Bartolo G, Malaguarnera G, et al. Vitamin D Serum Levels in Patients with Statin-Induced Musculoskeletal Pain. Dis Markers. 2019 Mar 25;2019:3549402. doi: 10.1155/2019/3549402. eCollection 2019.

32. Abdul-Razzak KK, Alshogran OY, Altawalbeh SM, et al. Overactive bladder and associated psychological symptoms: A possible link to vitamin D and calcium. Neurourol Urodyn. 2019 Apr;38(4):1160-7. doi: 10.1002/nau.23975. Epub 2019 Mar 14.

33. Kucukceran H, Ozdemir O, Kiral S, et al. The impact of circulating 25-hydroxyvitamin and oral cholecalciferol treatment on menstrual pain in dysmenorrheic patients. Gynecol Endocrinol. 2019 Jan;35(1):53-7. doi: 10.1080/09513590.2018.1490407. Epub 2018 Jul 25

34. Eloqayli H, Al-Yousef A, Jaradat R. Vitamin D and ferritin correlation with chronic neck pain using standard statistics and a novel artificial neural network prediction model. Br J Neurosurg. 2018 Apr;32(2):172-6. doi: 10.1080/02688697.2018.1436691. Epub 2018 Feb 15.

35. Prakash S, Rathore C, Makwana P, et al. Vitamin D Deficiency in Patients With Chronic Tension-Type Headache: A Case-Control Study. Headache. 2017 Jul;57(7):1096-108. doi: 10.1111/head.13096. Epub 2017 May 3.

36. Ellis SD, Kelly ST, Shurlock JH, Hepburn ALN. The role of vitamin D testing and replacement in fibromyalgia: a systematic literature review. BMC Rheumatol. 2018 Oct 5;2:28. doi: 10.1186/s41927-018-0035-6. eCollection 2018.

37. Yong WC, Sanguankeo A, Upala S. Effect of vitamin D supplementation in chronic widespread pain: a systematic review and meta-analysis. Clin Rheumatol. 2017 Dec;36(12):2825-33. doi: 10.1007/s10067-0173754-y. Epub 2017 Aug 15.

38. Singla M, Rastogi A, Aggarwal AN, et al. Vitamin D supplementation improves simvastatin-mediated decline in exercise performance: A randomized double-blind placebo-controlled study. J Diabetes. 2017 Dec;9(12):1100-6. doi: 10.1111/1753-0407.12541. Epub 2017 Jun 28.

39. Brady SRE, Naderpoor N, de Courten MPJ, et al. Vitamin D supplementation may improve back pain disability in vitamin D deficient and overweight or obese adults. J Steroid Biochem Mol Biol. 2019 Jan;185:212-7. doi: 10.1016/j.jsbmb.2018.09.005. Epub 2018 Sep 7.

40. Dzik K, Skrobot W, Flis DJ, et al. Vitamin D supplementation attenuates oxidative stress in paraspinal skeletal muscles in patients with low back pain. Eur J Appl Physiol. 2018 Jan;118(1):143-51. doi: 10.1007/s00421-017-3755-1. Epub 2017 Nov 15.

41. Manoy P, Yuktanandana P, Tanavalee A, et al. Vitamin D Supplementation Improves Quality of Life and Physical Performance in Osteoarthritis Patients. Nutrients. 2017 Jul 26;9(8):799. doi: 10.3390/nu9080799

42. Gao XR, Chen YS, Deng W. The effect of vitamin D supplementation on knee osteoarthritis: A meta-analysis of randomized controlled trials. Int J Surg. 2017 Oct;46:14-20. doi: 10.1016/j.ijsu.2017.08.010. Epub 2017 Aug 7.

43. Fedin AI, Starykh EP, Putilin MV, et al. Endothelial dysfunction in patients with chronic cerebral ischemia and possibilities of its pharmacological correction of the. Lechashchiy vrach. 2015;(5):15-8 (In Russ.).

44. Rizka A, Setiati S, Harimurti K, et al. Effect of Alfacalcidol on Inflammatory markers and T Cell Subsets in Elderly with Frailty Syndrome: a Double Blind Randomized Controlled Trial. Acta Med Indones. 2018 Jul;50(3):215-21.

45. Grange F, Mitschler A, Genestier S, Guillaume JC. Acne prurigineuse grave chez l'insuffisant renal dialyse. Difficultes diagnostiques et efficacite de l'isotretinoine [Severe pruriginous acne in dialysed renal failure. Diagnostic difficulties and efficacy of isotretinoin]. Ann Dermatol Venereol. 2001 Nov;128(11):1215-9 (In French).

46. Ahmed Mohamed A, Salah Ahmed EM, Abdel-Aziz RTA, et al. The impact of active vitamin D administration on the clinical outcomes of acne vulgaris. J Dermatolog Treat. 2020 Jan 3;1-6. doi: 10.1080/09546634.2019.1708852. Online ahead of print.

47. Ringe JD, Farahmand P, Schacht E, Rozehnal A. Superiority of a combined treatment of Alendronate and Alfacalcidol compared to the combination of Alendronate and plain vitamin D or Alfacalcidol alone in established postmenopausal or male osteoporosis (AAC-Trial). Rheumatol Int. 2007 Mar;27(5):425-34. doi: 10.1007/s00296-0060288-z

48. Ringe JD, Farahmand P, Schacht E. Alfacalcidol in men with osteoporosis: a prospective, observational, 2-year trial on 214 patients. Rheumatol Int. 2013 Mar;33(3):637-43. doi: 10.1007/s00296-012-2429-x. Epub 2012 Apr 8.

49. Yamauchi Y, Tsunematsu T, Konda S, et al. [A double blind trial of alfacalcidol on patients with rheumatoid arthritis (RA)]. Ryumachi. 1989 Feb;29(1):11-24 (In Japan).

50. Registr lekarstvennykh sredstv Rossii RLS Entsiklopediya lekarstv, instruktsiya po meditsinskomu primeneniyu preparata, Registratsionnyy nomer: LSR-007813/10-100810 [Register of Medicines of Russia Radar Station Encyclopedia of Medicines, instructions for medical use of the drug, Registration number: ЛСР -007813/10-100810]. Available from: (accessed 10.12.2020) (In Russ.).


For citations:

Gromova O.A., Torshin I.Yu., Putilina M.V., Sardaryan I.S., Fedotova L.E., Limanova O.A. Nociception: the roles of vitamin D. Neurology, Neuropsychiatry, Psychosomatics. 2021;13(1):145-153. (In Russ.)

Views: 441

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)