The Preoperative Supplementation With Vitamin D Attenuated Pain Intensity and Reduced the Level of Pro-inflammatory Markers in Patients After Posterior Lumbar Interbody Fusion

Katarzyna Krasowska, Wojciech Skrobot, Ewelina Liedtke, Piotr Sawicki, Damian Jozef Flis, Katarzyna Patrycja Dzik, Witold Libionka, Wojciech Kloc, Jan Jacek Kaczor, Katarzyna Krasowska, Wojciech Skrobot, Ewelina Liedtke, Piotr Sawicki, Damian Jozef Flis, Katarzyna Patrycja Dzik, Witold Libionka, Wojciech Kloc, Jan Jacek Kaczor

Abstract

The aim of this experimental study was to assess whether 5 weeks of preoperative supplementation with vitamin D affects the intensity of pain and the level of inflammatory markers in patients undergoing posterior lumbar interbody fusion (PLIF) followed by rehabilitation. 42 patients were divided, by double-blind randomization, into two groups: supplemented (SUPL) vitamin D (3200 IU dose of vitamin D/day for 5 weeks) and placebo group (PL) treated with vegetable oil. The 10-week program of early rehabilitation (3 times a week) was initiated 4 weeks following PLIF. Measurements of serum 25(OH)D3 and CRP, IL-6, TNF-α, and IL-10 were performed. Pain intensity was measured using VAS. After supplementation with vitamin D serum, the concentration of 25(OH)D3 significantly increased in the SUPL group (∗ p < 0.005) and was significantly higher as compared to the PL group (∗ p < 0.001). A significant reduction in pain intensity was observed 4 weeks after surgery and after rehabilitation in both groups. In the SUPL group, serum CRP and IL-6 concentration significantly decreased after rehabilitation, compared with the postsurgical level (a p < 0.04). The level of TNF-α was significantly lower after rehabilitation only in the supplemented group (∗ p < 0.02). There were no significant changes in the IL-10 level in both groups during the study. Our data indicate that supplementation with vitamin D may reduce systemic inflammation and when combined with surgery and early postsurgical rehabilitation, it may decrease the intensity of pain in LBP patients undergoing PLIF. Data indicate that LBP patients undergoing spine surgery should use vitamin D perioperatively as a supplement.

Keywords: VAS; early rehabilitation; inflammatory cytokines; low back pain; vitamin D.

Figures

FIGURE 1
FIGURE 1
The timelines of the program.
FIGURE 2
FIGURE 2
The concentration of vitamin D in serum of LBP patients. Results were expressed as mean ± SEM. SUPL (n = 18), PL (n = 21), ∗p < 0.001 – difference between the means between indicated groups. ap < 0.005 – difference between the indicated results/mean and T1 SUPL. bp < 0.05 – difference between the indicated results/mean and T1 SUPL. cp < 0.0002 – difference between the indicated results/mean and T2 SUPL. Ap < 0.03 – difference between the indicated results/mean and T1 PL.
FIGURE 3
FIGURE 3
The effect of vitamin D supplementation on VAS. Results were expressed as mean ± SEM, SUPL (n = 18), PL (n = 21); ap < 0.006 – difference between the indicated results/mean and T1 SUPL, bp < 0.0001 – difference between the indicated results/mean and T1 SUPL, dp < 0.002 – difference between the indicated results/mean and T2 SUPL. Ap < 0.05 – difference between the indicated results/mean and T1 PL. Bp < 0.0001 – difference between the indicated results/mean and T1 PL. Dp < 0.001 – difference between the indicated results/mean and T2 PL.
FIGURE 4
FIGURE 4
The serum CRP (A), IL-6 (B), TNF- α (C), and IL-10 (D) concentrations in LBP patients. Results were expressed as mean ± SEM. SUPL (n = 18), PL (n = 21); ∗p < 0.05 – difference between the means indicated groups; ap ≤ 0.04 – difference between the indicated results/mean and T3 SUPL, bp < 0.02 – difference between the indicated results/mean and T1 SUPL.
FIGURE 5
FIGURE 5
Possible mechanism(s) of vitamin D-dependent pain modulation include its anti-inflammatory effects mediated by the reduced cytokine(s). The sedentary lifestyle, obesity, elevated inflammation as well as paraspinal muscle atrophy and mitochondrial dysfunction (Dzik et al., 2018) reversely, are associated with vitamin D deficiency/insufficiency. We assume that above-listed factors intensify the pain in LBP patients. Preoperative vitamin D supplementation is accompanied by normalized serum vitamin D concentration, inhibition of muscle atrophy and restoration of mitochondrial function. After supplementation with vitamin D, the reduction of inflammation and alleviation of pain is observed in LBP patients after PLIF surgery followed by early rehabilitation. Taken together, our study support anti-inflammatory and pain-relieving actions of vitamin D that may promote the recovery process. ↓ – decrease of factor, ↑ – increase of factor, ⊣ – inhibition, blue arrows – negative interaction, green arrow – positive interaction/protocol time.

References

    1. Aglipay M., Birken C. S., Parkin P. C., Loeb M. B., Thorpe K., Chen Y., et al. (2017). Effect of high-dose vs standard-dose wintertime vitamin D supplementation on viral upper respiratory tract infections in young healthy children. JAMA 318 245–254. 10.1001/jama.2017.8708
    1. Al-Jarallah K., Shehab D., Abraham M., Mojiminiyi O. A., Abdella N. A. (2013). Musculoskeletal pain: should physicians test for vitamin D level? Int. J. Rheum. Dis. 16 193–197. 10.1111/1756-185X.12066
    1. Bang W. S., Lee D. H., Kim K. T., Cho D. C., Sung J. K., Han I. B., et al. (2018). Relationships between vitamin D and paraspinal muscle: human data and experimental rat model analysis. Spine J. 18 1053–1061. 10.1016/j.spinee.2018.01.007
    1. Bischoff-Ferrari H. A. (2012). Relevance of vitamin D in muscle health. Rev. Endocr. Metab. Disord. 13 71–77. 10.1007/s11154-011-9200-6
    1. Bluher M., Fasshauer M., Tonjes A., Kratzsch J., Schon M. R., Paschke R. (2005). Association of interleukin-6, C-reactive protein, interleukin-10 and adiponectin plasma concentrations with measures of obesity, insulin sensitivity and glucose metabolism. Exp. Clin. Endocrinol. Diabetes 113 534–537. 10.4161/adip.26553
    1. Borenstein D. G., O’Mara J. W., Jr., Boden S. D., Lauerman W. C., Jacobson A., Platenberg C., et al. (2001). The value of magnetic resonance imaging of the lumbar spine to predict low-back pain in asymptomatic subjects : a seven-year follow-up study. J. Bone Joint Surg. Am. 83-A 1306–1311. 10.2106/00004623-200109000-00002
    1. Brooks P. M. (2006). The burden of musculoskeletal disease–a global perspective. Clin. Rheumatol. 25 778–781. 10.1007/s10067-006-0240-3
    1. Canning M. O., Grotenhuis K., De Wit H., Ruwhof C., Drexhage H. A. (2001). 1-alpha,25-Dihydroxyvitamin D3 (1,25(OH)(2)D(3)) hampers the maturation of fully active immature dendritic cells from monocytes. Eur. J. Endocrinol. 145 351–357. 10.1530/eje.0.1450351
    1. Colombini A., Brayda-Bruno M., Lombardi G., Croiset S. J., Vrech V., Maione V., et al. (2014). FokI polymorphism in the vitamin D receptor gene (VDR) and its association with lumbar spine pathologies in the Italian population: a case-control study. PLoS One 9:e97027. 10.1371/journal.pone.0097027
    1. Colombini A., Lanteri P., Lombardi G., Grasso D., Recordati C., Lovi A., et al. (2012). Metabolic effects of vitamin D active metabolites in monolayer and micromass cultures of nucleus pulposus and annulus fibrosus cells isolated from human intervertebral disc. Int. J. Biochem. Cell Biol. 44 1019–1030. 10.1016/j.biocel.2012.03.012
    1. Croft P., Rigby A. S., Boswell R., Schollum J., Silman A. (1993). The prevalence of chronic widespread pain in the general population. J. Rheumatol. 20 710–713.
    1. Dahlquist D. T., Dieter B. P., Koehle M. S. (2015). Plausible ergogenic effects of vitamin D on athletic performance and recovery. J. Int. Soc. Sports Nutr. 12:33. 10.1186/s12970-015-0093-8
    1. D’Ambrosio D., Cippitelli M., Cocciolo M. G., Mazzeo D., Di Lucia P., Lang R., et al. (1998). Inhibition of IL-12 production by 1,25-dihydroxyvitamin D3. Involvement of NF-kappaB downregulation in transcriptional repression of the p40 gene. J. Clin. Invest. 101 252–262. 10.1172/jci1050
    1. Dzik K., Skrobot W., Flis D. J., Karnia M., Libionka W., Kloc W., et al. (2018). Vitamin D supplementation attenuates oxidative stress in paraspinal skeletal muscles in patients with low back pain. Eur. J. Appl. Physiol. 118 143–151. 10.1007/s00421-017-3755-1
    1. Dzik K., Skrobot W., Kaczor K., Flis D. J., Karnia M., Libionka W., et al. (2019). Vitamin D deficiency is associated with muscle atrophy and reduced mitochondrial function in patients with chronic low back pain. Oxid. Med. Cell. Longev. (in press).
    1. Englund M., Persson J., Bergstrom I. (2017). Lower pain and higher muscular strength in immigrant women with vitamin D deficiency following vitamin D treatment. Int. J. Circumpolar Health 76:1340547. 10.1080/22423982.2017.1340547
    1. Girgis C. M., Clifton-Bligh R. J., Hamrick M. W., Holick M. F., Gunton J. E. (2013). The roles of vitamin D in skeletal muscle: form, function, and metabolism. Endocr. Rev. 34 33–83. 10.1210/er.2012-1012
    1. Holick M. F. (2007). Vitamin D deficiency. N. Engl. J. Med. 357 266–281.
    1. Holick M. F., Binkley N. C., Bischoff-Ferrari H. A., Gordon C. M., Hanley D. A., Heaney R. P., et al. (2011). Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 96 1911–1930. 10.1210/jc.2011-0385
    1. Hoy D., Brooks P., Blyth F., Buchbinder R. (2010). The epidemiology of low back pain. Best Pract. Res. Clin. Rheumatol. 24 769–781. 10.1016/j.berh.2010.10.002
    1. Hoy D., March L., Brooks P., Blyth F., Woolf A., Bain C., et al. (2014). The global burden of low back pain: estimates from the global burden of disease 2010 study. Ann. Rheum. Dis. 73 968–974. 10.1136/annrheumdis-2013-204428
    1. Jackson J. L., Judd S. E., Panwar B., Howard V. J., Wadley V. G., Jenny N. S., et al. (2016). Associations of 25-hydroxyvitamin D with markers of inflammation, insulin resistance and obesity in black and white community-dwelling adults. J. Clin. Transl. Endocrinol. 5 21–25. 10.1016/j.jcte.2016.06.002
    1. Koch A., Zacharowski K., Boehm O., Stevens M., Lipfert P., Von Giesen H. J., et al. (2007). Nitric oxide and pro-inflammatory cytokines correlate with pain intensity in chronic pain patients. Inflamm. Res. 56 32–37. 10.1007/s00011-007-6088-4
    1. Kruit A., Zanen P. (2016). The association between vitamin D and C-reactive protein levels in patients with inflammatory and non-inflammatory diseases. Clin. Biochem. 49 534–537. 10.1016/j.clinbiochem.2016.01.002
    1. Kwilasz A. J., Grace P. M., Serbedzija P., Maier S. F., Watkins L. R. (2015). The therapeutic potential of interleukin-10 in neuroimmune diseases. Neuropharmacology 96 55–69. 10.1016/j.neuropharm.2014.10.020
    1. Laird E., Mcnulty H., Ward M., Hoey L., Mcsorley E., Wallace J. M., et al. (2014). Vitamin D deficiency is associated with inflammation in older Irish adults. J. Clin. Endocrinol. Metab. 99 1807–1815. 10.1210/jc.2013-3507
    1. Mangin M., Sinha R., Fincher K. (2014). Inflammation and vitamin D: the infection connection. Inflamm. Res. 63 803–819. 10.1007/s00011-014-0755-z
    1. Martin K. R., Reid D. M. (2017). Is there role for vitamin D in the treatment of chronic pain? Ther. Adv. Musculoskelet Dis. 9 131–135. 10.1177/1759720X17708124
    1. McBeth J., Jones K. (2007). Epidemiology of chronic musculoskeletal pain. Best Pract. Res. Clin. Rheumatol. 21 403–425. 10.1016/j.berh.2007.03.003
    1. McBeth J., Pye S. R., O’neill T. W., Macfarlane G. J., Tajar A., Bartfai G., et al. (2010). Musculoskeletal pain is associated with very low levels of vitamin D in men: results from the european male ageing study. Ann. Rheum. Dis. 69 1448–1452. 10.1136/ard.2009.116053
    1. Metzger M. F., Kanim L. E., Zhao L., Robinson S. T., Delamarter R. B. (2015). The relationship between serum vitamin D levels and spinal fusion success: a quantitative analysis. Spine 40 E458–E468. 10.1097/BRS.0000000000000801
    1. Milligan E. D., Penzkover K. R., Soderquist R. G., Mahoney M. J. (2012). Spinal interleukin-10 therapy to treat peripheral neuropathic pain. Neuromodulation 15 520–526. 10.1111/j.1525-1403.2012.00462.x
    1. Napiorkowska L., Budlewski T., Jakubas-Kwiatkowska W., Hamzy V., Gozdowski D., Franek E. (2009). Prevalence of low serum vitamin D concentration in an urban population of elderly women in Poland. Pol. Arch. Med. Wewn. 119 699–703.
    1. Okifuji A., Hare B. D. (2015). The association between chronic pain and obesity. J. Pain Res. 8 399–408. 10.2147/JPR.S55598
    1. Pludowski P., Holick M. F., Grant W. B., Konstantynowicz J., Mascarenhas M. R., Haq A., et al. (2018). Vitamin D supplementation guidelines. J. Steroid Biochem. Mol. Biol. 175 125–135. 10.1016/j.jsbmb.2017.01.021
    1. Rusinska A., Pludowski P., Walczak M., Borszewska-Kornacka M. K., Bossowski A., Chlebna-Sokol D., et al. (2018). Vitamin D supplementation guidelines for general population and groups at risk of vitamin d deficiency in poland-recommendations of the polish society of pediatric endocrinology and diabetes and the expert panel with participation of national specialist consultants and representatives of scientific societies-2018 update. Front. Endocrinol. 9:246. 10.3389/fendo.2018.00246
    1. Schleithoff S. S., Zittermann A., Tenderich G., Berthold H. K., Stehle P., Koerfer R. (2006). Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am. J. Clin. Nutr. 83 754–759.
    1. Schwalfenberg G. (2007). Not enough vitamin D: health consequences for Canadians. Can. Fam. Physician 53 841–854.
    1. Steffens D., Maher C. G., Pereira L. S., Stevens M. L., Oliveira V. C., Chapple M., et al. (2016). Prevention of low back pain: a systematic review and meta-analysis. JAMA Intern. Med. 176 199–208. 10.1001/jamainternmed.2015.7431
    1. Stoker G. E., Buchowski J. M., Bridwell K. H., Lenke L. G., Riew K. D., Zebala L. P. (2013). Preoperative vitamin D status of adults undergoing surgical spinal fusion. Spine 38 507–515. 10.1097/BRS.0b013e3182739ad1
    1. Tao R. X., Zhou Q. F., Xu Z. W., Hao J. H., Huang K., Mou Z., et al. (2015). Inverse correlation between vitamin D and C-reactive protein in newborns. Nutrients 7 9218–9228. 10.3390/nu7115468
    1. Vincent H. K., Ben-David K., Conrad B. P., Lamb K. M., Seay A. N., Vincent K. R. (2012). Rapid changes in gait, musculoskeletal pain, and quality of life after bariatric surgery. Surg. Obes. Relat. Dis. 8 346–354. 10.1016/j.soard.2011.11.020
    1. von Kanel R., Muller-Hartmannsgruber V., Kokinogenis G., Egloff N. (2014). Vitamin D and central hypersensitivity in patients with chronic pain. Pain Med. 15 1609–1618. 10.1111/pme.12454
    1. Vos T., Flaxman A. D., Naghavi M., Lozano R., Michaud C., Ezzati M., et al. (2012). Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the global burden of disease study 2010. Lancet 380 2163–2196. 10.1016/S0140-6736(12)61729-2
    1. Waterhouse M., Tran B., Ebeling P. R., English D. R., Lucas R. M., Venn A. J., et al. (2015). Effect of vitamin D supplementation on selected inflammatory biomarkers in older adults: a secondary analysis of data from a randomised, placebo-controlled trial. Br. J. Nutr. 114 693–699. 10.1017/S0007114515002366
    1. Zerwekh J. E. (2008). Blood biomarkers of vitamin D status. Am. J. Clin. Nutr. 87 1087S–1091S. 10.1093/ajcn/87.4.1087s

Source: PubMed

3
구독하다