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Minimally Invasive Spine Procedures

Perspective on Intradiscal Therapies for Lumbar Discogenic Pain: State of the Science, Knowledge Gaps, and Imperatives for Clinical Adoption

, , , ORCID Icon & ORCID Icon
Pages 1171-1182 | Received 20 Sep 2023, Accepted 07 Mar 2024, Published online: 18 Mar 2024

References

  • Fine N, Lively S, Seguin CA, Perruccio AV, Kapoor M, Rampersaud R. Intervertebral disc degeneration and osteoarthritis: a common molecular disease spectrum. Nat Rev Rheumatol. 2023;19(3):136–152. doi:10.1038/s41584-022-00888-z
  • Lorio MP, Beall DP, Calodney AK, Lewandrowski KU, Block JE, Mekhail N. Defining the patient with lumbar discogenic pain: real-world implications for diagnosis and effective clinical management. J Pers Med. 2023;13(5):821. doi:10.3390/jpm13050821
  • Bogduk N. Degenerative joint disease of the spine. Radiol Clin North Am. 2012;50(4):613–628. doi:10.1016/j.rcl.2012.04.012
  • Bogduk N. On the definitions and physiology of back pain, referred pain, and radicular pain. Pain. 2009;147(1–3):17–19. doi:10.1016/j.pain.2009.08.020
  • Manchikanti L, Singh V, Pampati V, et al. Evaluation of the relative contributions of various structures in chronic low back pain. Pain Physician. 2001;4(4):308–316. doi:10.36076/ppj.2001/4/308
  • 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(17):1878–1883. doi:10.1097/00007632-199509000-00007
  • Her YF, Kubrova E, Martinez Alvarez GA, D’Souza RS. The analgesic efficacy of intradiscal injection of bone marrow aspirate concentrate and culture-expanded bone marrow mesenchymal stromal cells in discogenic pain: a systematic review. J Pain Res. 2022;15:3299–3318. doi:10.2147/JPR.S373345
  • Hickman TT, Rathan-Kumar S, Peck SH. Development, pathogenesis, and regeneration of the intervertebral disc: current and future insights spanning traditional to omics methods. Front Cell Dev Biol. 2022;10:841831. doi:10.3389/fcell.2022.841831
  • Muthu S, Jeyaraman M, Chellamuthu G, Jeyaraman N, Jain R, Khanna M. Does the intradiscal injection of platelet rich plasma have any beneficial role in the management of lumbar disc disease? Global Spine J. 2022;12(3):503–514. doi:10.1177/2192568221998367
  • Peng B, Xu B, Wu W, Du L, Zhang T, Zhang J. Efficacy of intradiscal injection of platelet-rich plasma in the treatment of discogenic low back pain: a single-arm meta-analysis. Medicine. 2023;102(10):e33112. doi:10.1097/MD.0000000000033112
  • Sakai D, Andersson GB. Stem cell therapy for intervertebral disc regeneration: obstacles and solutions. Nat Rev Rheumatol. 2015;11(4):243–256. doi:10.1038/nrrheum.2015.13
  • Sakai D, Schol J, Watanabe M. Clinical development of regenerative medicine targeted for intervertebral disc disease. Medicina. 2022;58(2):267. doi:10.3390/medicina58020267
  • Schneider BJ, Hunt C, Conger A, et al. The effectiveness of intradiscal biologic treatments for discogenic low back pain: a systematic review. Spine J. 2022;22(2):226–237. doi:10.1016/j.spinee.2021.07.015
  • Schol J, Sakai D. Comprehensive narrative review on the analysis of outcomes from cell transplantation clinical trials for discogenic low back pain. N Am Spine Soc J. 2023;13:100195. doi:10.1016/j.xnsj.2022.100195
  • Xie B, Chen S, Xu Y, et al. Clinical efficacy and safety of human mesenchymal stem cell therapy for degenerative disc disease: a systematic review and meta-analysis of randomized controlled trials. Stem Cells Int. 2021;2021:9149315. doi:10.1155/2021/9149315
  • Johnson WE, Caterson B, Eisenstein SM, Hynds DL, Snow DM, Roberts S. Human intervertebral disc aggrecan inhibits nerve growth in vitro. Arthritis Rheum. 2002;46(10):2658–2664. doi:10.1002/art.10585
  • Johnson WE, Caterson B, Eisenstein SM, Roberts S. Human intervertebral disc aggrecan inhibits endothelial cell adhesion and cell migration in vitro. Spine. 2005;30(10):1139–1147. doi:10.1097/01.brs.0000162624.95262.73
  • Kepler CK, Ponnappan RK, Tannoury CA, Risbud MV, Anderson DG. The molecular basis of intervertebral disc degeneration. Spine J. 2013;13(3):318–330. doi:10.1016/j.spinee.2012.12.003
  • Alini M, Diwan AD, Erwin WM, Little CB, Melrose J. An update on animal models of intervertebral disc degeneration and low back pain: exploring the potential of artificial intelligence to improve research analysis and development of prospective therapeutics. JOR Spine. 2023;6(1):e1230. doi:10.1002/jsp2.1230
  • Setton LA, Chen J. Mechanobiology of the intervertebral disc and relevance to disc degeneration. J Bone Joint Surg Am. 2006;88(Suppl 2):52–57. doi:10.2106/JBJS.F.00001
  • Food and Drug Administration. Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use. Guidance for industry and Food and Drug Administration staff; 2020.
  • Coric D, Pettine K, Sumich A, Boltes MO. Prospective study of disc repair with allogeneic chondrocytes presented at the 2012 Joint Spine Section Meeting. J Neurosurg Spine. 2013;18(1):85–95. doi:10.3171/2012.10.SPINE12512
  • Tuakli-Wosornu YA, Terry A, Boachie-Adjei K, et al. Lumbar Intradiskal Platelet-Rich Plasma (PRP) injections: a prospective, double-blind, randomized controlled study. PM R. 2016;8(1):1–10; quiz 10. doi:10.1016/j.pmrj.2015.08.010
  • Zielinski MA, Evans NE, Bae H, et al. Safety and Efficacy of platelet rich plasma for treatment of lumbar discogenic pain: a prospective, multicenter, randomized, double-blind study. Pain Physician. 2022;25(1):29–34.
  • Noriega DC, Ardura F, Hernandez-Ramajo R, et al. Treatment of degenerative disc disease with allogeneic mesenchymal stem cells: long-term follow-up results. Transplantation. 2021;105(2):e25–e27. doi:10.1097/TP.0000000000003471
  • Noriega DC, Ardura F, Hernandez-Ramajo R, et al. Intervertebral disc repair by allogeneic mesenchymal bone marrow cells: a randomized controlled trial. Transplantation. 2017;101(8):1945–1951. doi:10.1097/TP.0000000000001484
  • Schulz KF, Chalmers I, Altman DG. The landscape and lexicon of blinding in randomized trials. Ann Intern Med. 2002;136(3):254–259. doi:10.7326/0003-4819-136-3-200202050-00022
  • Schulz KF, Grimes DA. Blinding in randomised trials: hiding who got what. Lancet. 2002;359(9307):696–700. doi:10.1016/S0140-6736(02)07816-9
  • Amirdelfan K, Bae H, McJunkin T, et al. Allogeneic mesenchymal precursor cells treatment for chronic low back pain associated with degenerative disc disease: a prospective randomized, placebo-controlled 36-month study of safety and efficacy. Spine J. 2021;21(2):212–230. doi:10.1016/j.spinee.2020.10.004
  • Beall DP, Davis T, DePalma MJ, et al. Viable Disc tissue allograft supplementation; one- and two-level treatment of degenerated intervertebral discs in patients with chronic discogenic low back pain: one year results of the vast randomized controlled trial. Pain Physician. 2021;24(6):465–477.
  • Beall DP, Wilson GL, Bishop R, Tally W. VAST clinical trial: safely supplementing tissue lost to degenerative disc disease. Int J Spine Surg. 2020;14(2):239–253. doi:10.14444/7033
  • Hunter CW, Guyer R, Froimson M, DePalma MJ. Effect of age on outcomes after allogeneic disc tissue supplementation in patients with chronic discogenic low back pain in the VAST trial. Pain Manag. 2022;12(3):301–311. doi:10.2217/pmt-2021-0078
  • Altman RD, Devji T, Bhandari M, Fierlinger A, Niazi F, Christensen R. Clinical benefit of intra-articular saline as a comparator in clinical trials of knee osteoarthritis treatments: a systematic review and meta-analysis of randomized trials. Semin Arthritis Rheum. 2016;46(2):151–159. doi:10.1016/j.semarthrit.2016.04.003
  • Bar-Or D, Rael LT, Brody EN. Use of saline as a placebo in intra-articular injections in osteoarthritis: potential contributions to nociceptive pain relief. Open Rheumatol J. 2017;11(1):16–22. doi:10.2174/1874312901711010016
  • Saltzman BM, Leroux T, Meyer MA, et al. The therapeutic effect of intra-articular normal saline injections for knee osteoarthritis: a meta-analysis of evidence level 1 studies. Am J Sports Med. 2017;45(11):2647–2653. doi:10.1177/0363546516680607
  • Fabre H, Ducret M, Degoul O, et al. Characterization of different sources of human MSCs expanded in serum-free conditions with quantification of chondrogenic induction in 3D. Stem Cells Int. 2019;2019:2186728. doi:10.1155/2019/2186728
  • Mohamed-Ahmed S, Fristad I, Lie SA, et al. Adipose-derived and bone marrow mesenchymal stem cells: a donor-matched comparison. Stem Cell Res Ther. 2018;9(1):168. doi:10.1186/s13287-018-0914-1
  • Williams RJ, Tryfonidou MA, Snuggs JW, Le Maitre CL. Cell sources proposed for nucleus pulposus regeneration. JOR Spine. 2021;4(4):e1175. doi:10.1002/jsp2.1175
  • Gay MH, Mehrkens A, Rittmann M, et al. Nose to back: compatibility of nasal chondrocytes with environmental conditions mimicking a degenerated intervertebral disc. Eur Cell Mater. 2019;37:214–232. doi:10.22203/eCM.v037a13
  • Vadala G, Sowa G, Hubert M, Gilbertson LG, Denaro V, Kang JD. Mesenchymal stem cells injection in degenerated intervertebral disc: cell leakage may induce osteophyte formation. J Tissue Eng Regen Med. 2012;6(5):348–355. doi:10.1002/term.433
  • Risbud MV, Schipani E, Shapiro IM. Hypoxic regulation of nucleus pulposus cell survival: from niche to notch. Am J Pathol. 2010;176(4):1577–1583. doi:10.2353/ajpath.2010.090734
  • Colella F, Garcia JP, Sorbona M, et al. Drug delivery in intervertebral disc degeneration and osteoarthritis: selecting the optimal platform for the delivery of disease-modifying agents. J Control Release. 2020;328:985–999. doi:10.1016/j.jconrel.2020.08.041
  • Filler AG. Emergence and optimization of upright posture among hominiform hominoids and the evolutionary pathophysiology of back pain. Neurosurg Focus. 2007;23(1):1–6. doi:10.3171/FOC-07/07/E4
  • Pennisi E. Evolutionary biology. The burdens of being a biped. Science. 2012;336(6084):974. doi:10.1126/science.336.6084.974
  • Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J, Boos N. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine. 2001;26(17):1873–1878. doi:10.1097/00007632-200109010-00011
  • Lotz JC, Haughton V, Boden SD, et al. New treatments and imaging strategies in degenerative disease of the intervertebral disks. Radiology. 2012;264(1):6–19. doi:10.1148/radiol.12110339
  • Kushchayev SV, Glushko T, Jarraya M, et al. ABCs of the degenerative spine. Insights Imaging. 2018;9(2):253–274. doi:10.1007/s13244-017-0584-z
  • International Spine Intervention Society. Lumbar disc stimulation (Provocation Discography). In: Bogduk N, editor. Practice Guidelines for Spinal Diagnostic and Treatment Procedures. 1st ed. San Francisco: International Spine Intervention Society; 2004:20–46.
  • Rossi MJ, Brand JC, Lubowitz JH. Minimally Clinically Important Difference (MCID) is a low bar. Arthroscopy. 2023;39(2):139–141. doi:10.1016/j.arthro.2022.11.001
  • Adindu EK, Singh D, Geck M, Stokes J, Truumees E. Minimal clinically important difference and patient-acceptable symptom state in orthopaedic spine surgery: a review. JBJS Rev. 2023;11(4). doi:10.2106/JBJS.RVW.22.00200
  • Tubach F, Dougados M, Falissard B, Baron G, Logeart I, Ravaud P. Feeling good rather than feeling better matters more to patients. Arthritis Rheum. 2006;55(4):526–530. doi:10.1002/art.22110
  • Pham T, Tubach F. Patient acceptable symptomatic state (PASS). Joint Bone Spine. 2009;76(4):321–323. doi:10.1016/j.jbspin.2009.03.008
  • Daste C, Abdoul H, Foissac F, et al. Patient acceptable symptom state for patient-reported outcomes in people with non-specific chronic low back pain. Ann Phys Rehabil Med. 2022;65(1):101451. doi:10.1016/j.rehab.2020.10.005
  • Tubach F, Ravaud P, Martin-Mola E, et al. Minimum clinically important improvement and patient acceptable symptom state in pain and function in rheumatoid arthritis, ankylosing spondylitis, chronic back pain, hand osteoarthritis, and Hip and knee osteoarthritis: results from a prospective multinational study. Arthritis Care Res. 2012;64(11):1699–1707.
  • Ostelo RW, Deyo RA, Stratford P, et al. Interpreting change scores for pain and functional status in low back pain. Towards international consensus regarding minimal important change. Spine. 2008;33(1):90–94. doi:10.1097/BRS.0b013e31815e3a10
  • Glassman SD, Copay AG, Berven SH, Polly DW, Subach BR, Carreon LY. Defining substantial clinical benefit following lumbar spine arthrodesis. J Bone Joint Surg Am. 2008;90(9):1839–1847. doi:10.2106/JBJS.G.01095
  • Power JD, Perruccio AV, Canizares M, et al. Determining minimal clinically important difference estimates following surgery for degenerative conditions of the lumbar spine: analysis of the Canadian Spine Outcomes and Research Network (CSORN) registry. Spine J. 2023;23(9):1323–1333. doi:10.1016/j.spinee.2023.05.001
  • Solberg T, Johnsen LG, Nygaard OP, Grotle M. Can we define success criteria for lumbar disc surgery?: estimates for a substantial amount of improvement in core outcome measures. Acta Orthop. 2013;84(2):196–201. doi:10.3109/17453674.2013.786634
  • Werner DAT, Grotle M, Gulati S, et al. Criteria for failure and worsening after surgery for lumbar disc herniation: a multicenter observational study based on data from the Norwegian Registry for Spine Surgery. Eur Spine J. 2017;26(10):2650–2659. doi:10.1007/s00586-017-5185-5
  • Yin W, Pauza K, Olan WJ, Doerzbacher JF, Thorne KJ. Intradiscal injection of fibrin sealant for the treatment of symptomatic lumbar internal disc disruption: results of a prospective multicenter pilot study with 24-month follow-up. Pain Med. 2014;15(1):16–31. doi:10.1111/pme.12249
  • Beall DP, Amirdelfan K, Nunley PD, Phillips TR, Imaz Navarro LC, Spath A. Hydrogel augmentation of the lumbar intervertebral disc: an early feasibility study of a treatment for discogenic low back pain. J Vasc Interv Radiol. 2024;35(1):51–58 e51. doi:10.1016/j.jvir.2023.09.018
  • Kanan M, Eby O, Kelkar A, et al. Electrical stimulation-mediated tissue healing in porcine intervertebral disc under mechanically dynamic organ culture conditions. Spine. 2022;47(10):764–772. doi:10.1097/BRS.0000000000004331
  • Vadala G, Ambrosio L, Russo F, Papalia R, Denaro V. Stem Cells and intervertebral disc regeneration overview-what they can and can’t do. Int J Spine Surg. 2021;15(s1):40–53. doi:10.14444/8054
  • Paez A, Rovers M, Hutchison K, et al. Beyond the RCT: when are randomized trials unnecessary for new therapeutic devices, and what should we do instead? Ann Surg. 2022;275(2):324–331. doi:10.1097/SLA.0000000000005053
  • Abraham I, Lewandrowski KU, Elfar JC, et al. Randomized clinical trials and observational tribulations: providing clinical evidence for personalized surgical pain management care models. J Pers Med. 2023;13(7):1044. doi:10.3390/jpm13071044
  • Lewandrowski KU, Leon JF, Dowling A, et al. Breaking through the glass ceiling effect of high-grade clinical evidence creation in orthopaedics & trauma. Revista Colombiana de Ortopedia y Traumatología. 2022;36(4):215–228. doi:10.1016/j.rccot.2022.10.003
  • Hutchinson N, Moyer H, Zarin DA, Kimmelman J. The proportion of randomized controlled trials that inform clinical practice. Elife. 2022;2:11.
  • Fanaroff AC, Califf RM, Harrington RA, et al. Randomized trials versus common sense and clinical observation: JACC review topic of the week. J Am Coll Cardiol. 2020;76(5):580–589. doi:10.1016/j.jacc.2020.05.069