Ann Rehabil Med.  2012 Oct;36(5):657-664.

Effect of Intradiscal Methylene Blue Injection for the Chronic Discogenic Low Back Pain: One Year Prospective Follow-up Study

• Kim SH
• Ahn SH
• Cho YW
• Lee DG

Abstract

OBJECTIVE
To evaluate the efficacy of intradiscal methylene blue (MB) injection in patients with chronic discogenic low back pain. METHOD: Twenty patients with discogenic low back pain (4 males, 16 females; mean age 45.6 years) refractory to conservative management were recruited. All subjects underwent MB injection in target lumbar intervertebral discs confirmed by provocative discography. The clinical outcome was assessed by visual analog scale (VAS) and Oswestry disability index (ODI) at baseline and 1, 3, 6 and 12 months after treatment. Successful outcome was described as minimum of 2 points reduction in pain intensity compared with the baseline.
RESULTS
VAS and ODI significantly decreased after one injection. The average VAS and ODI were reduced significantly from 5.1 and 38.0 at baseline to 3.2 and 27.4 at 3 months after injection (p<0.05). However, the mean score of VAS at 12 month follow-up was 4.5 and we could not observe any difference between 12 months after injection and pretreatment. Eleven of twenty patients (55%) reported successful outcomes after intradiscal MB injection at 3 month follow up and the average VAS was reduced by 3.3+/-1.1 (p<0.05). At the time of 12 month follow up, pain had relapsed in 6 patients who have had satisfactory effect at 3 month follow up. Successful outcome was maintained in only 5 patients (20%) for 1 year.
CONCLUSION
The intradiscal MB injection is a short-term effective minimally invasive treatment indicated for discogenic back pain but it may lose its effectiveness long-term.

Keyword

Intradiscal methylene blue injection; Discogenic low back pain

MeSH Terms

Back Pain
Follow-Up Studies
Humans
Intervertebral Disc
Low Back Pain
Male
Methylene Blue
Prospective Studies
Methylene Blue

Figure

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  Fig. 1 Changes of the visual analog scale (VAS) and Oswestry disability index (ODI) in patients after intradiscal methylene blue (MB) injection. *p<0.05.

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  Fig. 2 Changes of the visual analog scale (VAS) after intradiscal methylene blue (MB) injection.

Reference

1. Andersson GB. Epidemiologic features of chronic low back pain. Lancet. 1999; 354:581–585. PMID: 10470716.

2. Schwarzer AC, Aprill CN, Derby R, Fortin J, Kine G, Bogduk N. The prevalence and clinical features of internal disc disruption in patients with chronic low back pain. Spine. 1995; 20:1878–1883. PMID: 8560335.

3. Andersson GB. Epidemiology of low back pain. Acta Orthop Scand Suppl. 1998; 281:28–31. PMID: 9771538.

4. Peng B, Pang X, Wu Y, Zhao C, Song X. A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back pain. Pain. 2010; 149:124–129. PMID: 20167430.

5. Ito M, Incorvaia KM, Yu SF, Fredrickson BE, Yuan HA, Rosenbaum AE. Predictive signs of discogenic lumbar pain on magnetic resonance imaging with discography correlation. Spine. 1998; 23:1252–1260. PMID: 9636979.

6. Zhou YL, Abdi S. Diagnosis and minimally invasive treatment of lumbar discogenic pain - a review of the literature. Clin J Pain. 2006; 22:468–481. PMID: 16772802.

7. Saal JA. Natural history and nonoperative treatment of lumbar disc herniation. Spine. 1996; 21:2S–9S. PMID: 9112320.

8. Smith SE, Darden BV, Rhyne AL, Wood KE. Outcome of unoperated discogram positive low back pain. Spine. 1995; 20:1997–2001. PMID: 8578375.

9. Peng B, Wu W, Hou S, Li P, Zhang C, Yang Y. The pathogenesis of discogenic low back pain. J Bone Joint Surg Br. 2005; 87:62–67. PMID: 15686239.

10. Moneta GB, Videman T, Kaivanto K, Aprill C, Spivey M, Vanharanta H, Sachs BL, Guyer RD, Hochschuler SH, Raschbaum RF, et al. Reported pain during lumbar discography as a function of annular ruptures and disc degeneration. A re-analysis of 833 discograms. Spine. 1994; 19:1968–1974. PMID: 7997931.

11. Kallewaard JW, Terheggen MA, Groen GJ, Sluijter ME, Derby R, Kapural L, Mekhail N, van Kleef M. Discogenic low back pain. Pain Pract. 2010; 10:560–579. PMID: 20825564.

12. Pauza KJ, Howell S, Dreyfuss P, Peloza JH, Dawson K, Boqduk N. A randomized, placebo-controlled trial of intradiscal electrothermal therapy for the treatment of discogenic low back pain. Spine J. 2004; 4:27–35. PMID: 14749191.

13. Singh K, Ledet E, Carl A. Intradiscal therapy: a review of current treatment modalities. Spine. 2005; 30:S20–S26. PMID: 16138061.

14. Rohof O. Intradiscal pulsed radiofrequency application following provocative discography for the management of degenerative disc disease and concordant pain: a pilot study. Pain Pract. 2012; 12:342–349. PMID: 22008239.

15. Freeman BJ, Fraser RD, Cain CM, Hall DJ, Chapple DC. A randomized, double-blind, controlled trial: intradiscal electrothermal therapy versus placebo for the treatment of chronic discogenic low back pain. Spine. 2005; 30:2369–2378. PMID: 16261111.

16. Finch PM, Price LM, Drummond PD. Radiofrequency heating of painful annular disruptions: one-year outcomes. J Spinal Disord Tech. 2005; 18:6–13. PMID: 15687845.

17. McMillan MR, Patterson PA, Parker V. Percutaneous laser disc decompression for the treatment of discogenic lumbar pain and sciatica: a preliminary report with 3-month follow-up in a general pain clinic population. Photomed Laser Surg. 2004; 22:434–438. PMID: 15671719.

18. Skliarenko ET, Tarabanova LV, Pashkov EP. Cryotherapy of pain syndromes associated with degenerative-dystrophic diseases of the spine. Ortop Travmatol Protez. 1986; 10:28–31. PMID: 3808657.

19. Lee SH, Derby R, Sul D, Hong J, Kim GH, Kang S, Kim NH, Yoo SH, Lee SJ, Hong YK, et al. Efficacy of a new navigable percutaneous disc decompression device (L'DISQ) in patients with herniated nucleus pulposus related to radicular pain. Pain Med. 2011; 12:370–376. PMID: 21332936.

20. Wainwright M, Crossley KB. Methylene blue - a therapeutic dye for all seasons? J Chemother. 2002; 14:431–443. PMID: 12462423.

21. Cetin M, Duran B, Demirkoprulu N, Guvenal T, Erden O, Cetin A. Effects of diazeniumdiolates (NONOates) and methylene blue on the reduction of postoperative adhesion in rats. Gynecol Obstet Invest. 2004; 57:186–190. PMID: 14752212.

22. Heydrick SJ, Reed KL, Cohen PA, Aarons CB, Gower AC, Becker JM, Stucchi AF. Intraperitoneal administration of methylene blue attenuates oxidative stress, increases peritoneal fibrinolysis, and inhibits intraabdominal adhesion formation. J Surg Res. 2007; 143:311–319. PMID: 17826794.

23. Farouk R, Lee PW. Intradermal methylene blue injection for the treatment of intractable idiopathic pruritus ani. Br J Surg. 1997; 84:670. PMID: 9171759.

24. Mentes BB, Akin M, Leventoglu S, Gultekin FA, Oguz M. Intradermal methylene blue injection for the treatment of intractable idiopathic pruritus ani: results of 30 cases. Tech Coloproctol. 2004; 8:11–14. PMID: 15057582.

25. Farrokhi MR, Vasei M, Fareghbal S, Farrokhi N. The effect of methylene blue on peridural fibrosis formation after laminectomy in rats: an experimental novel study. Spine J. 2011; 11:147–152. PMID: 21296299.

26. National Toxicology Program. Toxicology and carcinogenesis studies of methylene blue trihydrate (Cas No. 7220-79-3) in F344/N rats and B6C3F1 mice (gavage studies). Natl Toxicol Program Tech Rep Ser. 2008; 540:1–224. PMID: 18685714.

27. Salman AE, Salman MA, Saricaoglu F, Akinci SB, Aypar Ü. Pain on injection of propofol: a comparison of methylene blue and lidocaine. J Clin Anesth. 2011; 23:270–274. PMID: 21663809.

28. Mayer B, Brunner F, Schmidt K. Inhibition of nitric oxide synthesis by methylene blue. Biochem Pharmacol. 1993; 45:367–374. PMID: 7679577.

29. Poveda L, Hottiger M, Boos N, Wuertz K. Peroxynitrite induces gene expression in intervertebral disc cells. Spine. 2009; 34:1127–1133. PMID: 19407676.

30. Liu GZ, Ishihara H, Osada R, Kimura T, Tsuji H. Nitric oxide mediates the change of proteoglycan synthesis in the human lumbar intervertebral disc in response to hydrostatic pressure. Spine. 2001; 26:134–141. PMID: 11154531.

31. Peng B, Zhang Y, Hou S, Wu W, Fu X. Intradiscal methylene blue injection for the treatment of chronic discogenic low back pain. Eur Spine J. 2007; 16:33–38. PMID: 16496191.

32. Kang JD, Stefanovic-Racic M, McIntyre LA, Georgescu HI, Evans CH. Toward a biochemical understanding of human intervertebral disc degeneration and herniation. Contributions of nitric oxide, interleukins, prostaglandin E2, and matrix metalloproteinases. Spine. 1997; 22:1065–1073. PMID: 9160463.

33. Farrar JT, Portenoy RK, Berlin JA, Kinman JL, Strom BL. Defining the clinically important difference in pain outcome measures. Pain. 2000; 88:287–294. PMID: 11068116.

34. Hägg O, Fritzell P, Nordwall A. The clinical importance of changes in outcome scores after treatment for chronic low back pain. Eur Spine J. 2003; 12:12–20. PMID: 12592542.

35. Buttermann GR. The effect of spinal steroid injections for degenerative disc disease. Spine J. 2004; 4:495–505. PMID: 15363419.

36. Khot A, Bowditch M, Powell J, Sharp D. The use of intradiscal steroid therapy for lumbar spinal discogenic pain: a randomized controlled trial. Spine. 2004; 29:833–837. PMID: 15082979.

37. Miller MR, Mathews RS, Reeves KD. Treatment of painful advanced internal lumbar disc derangement with intradiscal injection of hypertonic dextrose. Pain Physician. 2006; 9:115–121. PMID: 16703971.

38. Poppers PJ, Mastri AR, Lebeaux M, Covino BG. The effect of methylene blue on neural tissue. Anesthesiology. 1970; 33:335–340. PMID: 5454953.

39. Gross SW. Letter: neurological deficits resulting from intrathecal administration of methylene blue. Neuroradiology. 1974; 7:117. PMID: 4408272.

40. Sharr MM, Weller RO, Brice JG. Spinal cord necrosis after intrathecal injection of methylene blue. J Neurol Neurosurg Psychiatry. 1978; 41:384–386. PMID: 580618.