Neurogenic inflammation is the basis of discogenic low back pain. New advances in treating degenerative disk disease focus on biological reconstructive measures.

2. DISCOGENIC LOW BACK PAIN
DIAGNOSIS ANDTREATMENT
DR. REZA AMINNEJAD
ANESTHESIOLOGIST, PAIN PHYSICIAN

3. INTRODUCTION
• DLBP first reported by Crock.
• The etiology of LBP is multifactorial, but intervertebral disc (IVD)
degeneration is considered one of the primary causes of LBP accounting for
around 26–42% of patients with LBP.
• Degeneration of IVD starts in young adults and progresses with age and ongoing
degeneration under pathological insults.
• It is associated with a reduced capacity for intrinsic self-repair in the tissue,
including a decrease in NP progenitor cells.
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4. MECHANISM
• The onset of discogenic pain has been associated with increased
inflammation, inducing nociceptive nerve ingrowth into the aneural disc,
which contributes to the development of pain.
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5. CONTRIBUTING FACTORS
• Mechanical load
• Injury
• Low nutrition supply
• Genetics
• Smoking
• Obesity
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The IVD between adjacent vertebrae are secondary cartilaginous joints (symphyses)

7. • In general, only the outer third of the AF is innervated by sinuvertebral
nerves (SVN), formed by the union of a somatic root from the ventral
ramus and an autonomic root provided by the grey ramus.
• The NP has no nerve supply.
• Reduction of large vacuolated notochordal cells in the NP is considered
the initiation process of disc degeneration (1st decade of life).
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The degenerative events in IVD

9. LOW BACK PAIN
LBP is defined as “pain in the area on the posterior
aspect of the body from the lower margin of the
twelfth ribs to the lower gluteal folds with or without
pain referred into one or both lower limbs that lasts
for at least one day”
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11. • Patients with disc degeneration are two to three times more likely than those who do
not have a degenerative disc to experience back pain.
• Meanwhile, patients with continuous multi-level disc degeneration are more likely
to have LBP and have it more severe than those with skipped-level IVD degeneration
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12. DEGENERATIVE FEATURES OFTHE IVD AT A LATE STAGE
• Loss of disc height
• Formation of osteophyte
• Internuclear calcification, and endplate sclerosis as indicated by plain radiographs
• Reduced hydration as shown by reduced signals of T2-weighted MRI
• Loss of AF/NP demarcation
• Irregular cartilage layer
• Loss of horizontal trabeculae as indicated by MRI
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13. PIVOTAL ROLE IN THE DEVELOPMENT OF DISCOGENIC LBP
Increased severity of disc degeneration, in particular neurogenic
inflammation induced ingrowth of sensory nerve fibers
(hyperinnervation) along with sensitization of sensory nociceptive
processing at peripheral terminals, spinal and supraspinal levels
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15. DIAGNOSIS
• Mechanical LBP in the center of the low back, especially with loading (e.g., prolonged
standing/sitting, carrying a heavy load) and with minimal radiation (buttocks or thighs or above the
knees in a non-dermatomal distribution!)
• With referred leg pain, patients describe a deep tissue pain resulting from a sensation of expanding
pressure.
• This dull and deep pain improves with standing and lying flat and may be reduced with extension
and it worsens with sitting, driving, lumbar flexion, bending, twisting, Valsalva maneuver, and
coughing
• Positive provocation with sustained hip flexion
• Absence of motor/sensory/reflex change
• Positive discography
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16. Sclerotomal pain distribution patterns in referred leg pain of discogenic origin by vertebral
level (Adapted from Kellgren, J.H., Clin Sci 1939; 4: 35–46).
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17. DISCOGRAPHY
• Developed in the 1950s
• A minimally invasive diagnostic test
• Provocative diagnostic discogram : Intradiscal injection of contrast agents to reproduce
the patient’s pain
• Functional anesthetic discogram: Intradiscal injection of a very small dose of an anesthetic
agent to relieve the pain
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18. • Discography is not only essential prior to intradiscal treatments, but more importantly, it
has been used for decades to confirm a diagnosis of discogenic pain and differentiating it
from other pain generators.
• Provocative discography is often combined with computed tomography (i.e., CT
discogram) to identify the location and extent of annular disruption. Posterior and/or
posterolateral annular radial and/or concentric fissure(s) that extend to the outer
annular fibers (e.g., grade 3 out of 4 severity) account for over 70% of painful discs
• The false-positive rate for low-pressure (<20 psi) discography has been reported to be as
low as 6%.
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21. MRI FINDINGS
• High intensity signal in the posterior annulus on T2-weighted images, known as high
intensity zone (HIZ). The concept of a HIZ has been debated and it could be due to fluid
accumulation.
• Bulging or protruding discs
• Decreased disc signal intensity onT2-weighted images suggesting dehydration
• Type 1 Modic changes have been shown to have high specificity for positive
discography.
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22. SERUM BIOMARKERS
• C-C motif ligand 5
• C-X-C motif ligand 6
• IL-6
• High-sensitivity C-reactive protein
• TNF-a
• IL-1b
• Type 2 collagen
• Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS)
• Complement C3
• Fibrinogen
• Local biomarkers, substance P, neurofilament, and vasoactive-intestinal peptide immunoreactive nerve fibers
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23. NOVEL MRI METHODS
• Quantitative chemical exchange saturation transfer MRI (qCEST MRI) also has the potential to detect pH changes in
IVDs
• Ratio of R1ᵨ dispersion to CEST is also reported to have the potential to detect painful IVDs
• T2 mapping can be used as a quantitative diagnostic tool in disc degeneration and discogenic pain.
• MRIT2 relaxation time is a quantitative parameter that is sensitive to changes in collagen and water content in IVD.
• MRI T1ᵨ is associated with a loss of macromolecules and may be sensitive to early biochemical changes in IVD
degeneration
• Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a quantitative analysis of sulfated glycosaminoglycans with
cartilaginous tissue that has been applied to IVD
• Fixed-charge density of cartilage by sodium MRI (23Na MRI)
• Ultrashort time-to-echo (UTE) MRI assesses the MRI signal from short-T2 components
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if the DH discrepancy ratio is ≥ 6.04% in patients with early to middle stage disc
degeneration, we can suspect significant discogenic LBP.

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The DH discrepancy ratio was calculated as: (1- [calibrated DH on standing/calibrated DH on supine]) X 100 %

26. GOALS OF MANAGEMENT
• Improvement in pain threshold
• Improvement in function
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27. CURRENT TREATMENT MODALITIES
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28. • The aim of treatment in patients with LBP without neurological deficits is pain
management.
• Conservative treatments consist of pharmacological and nonpharmacological modalities.
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29. NON-PHARMACOLOGICAL TREATMENTS
• Current modalities of multimodal rehabilitation mainly consist of
exercise therapy combined with cognitive behavioral training and
are more effective in reducing disability and pain-related fear than exercise
therapy alone.
• Types of psychological treatments include cognitive behavioral therapy
(CBT), progressive relaxation, and Biofeedback.
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30. EXERCISETHERAPY
• Stretching exercises are most associated with pain reduction
• Strengthening exercises yields greatest functional gains
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31. LACKING RCTS
• lumbar support
• Massage therapy
• Back schools
• Traction
• Superficial heat or cold application
• Transcutaneous Electrical Nerve Stimulation (TENS)
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32. COMPLEMENTARY & ALTERNATIVE MEDICINE THERAPIES
• Acupuncture/dry needling
• Manipulation of the spine through osteopathic or chiropractic treatment
• Sleep support through medium-firm mattresses
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33. DR. REZA AMINNEJAD
33 There is still limited evidence for the efficacy of the McKenzie method in chronic LBP
Lam OT, Strenger DM, Chan-Fee M, Pham PT, Preuss RA, Robbins SM. Effectiveness of the McKenzie method of
mechanical diagnosis and therapy for treating low back pain: literature review with meta-analysis. J Orthop
Sports PhysTher. 2018; 48 (6): 476–90.

34. PHARMACOLOGICAL TREATMENTS
• NSAIDs
• Paracetamol and weak opioids (i.e.,tramadol)
• Neuropathic pain medications such as anticonvulsants and/or antidepressants
(i.e., gabapentin, pregabalin and duloxetine)
• Topical or patch forms of analgesia are effective, but there is no evidence of a
long-term benefit.
• The role of muscle relaxants is still conflicting, but we prefer using them in the
acute phase and short duration to relieve the muscle spasms in the acute phase.
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35. • While gabapentin has shown analgesic efficacy for chronic low back pain
with radiculopathy, only topiramate has been studied for chronic axial
low back pain with evidence of analgesia and improved quality of life.
• Topiramate has the advantageous side effect of weight loss, but is also
associated with dizziness, somnolence, and rare nephrolithiasis.
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36. INTERVENTIONAL PROCEDURES
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37. THE PREDICTORS OF POOR OUTCOMES
• Poorly controlled psychiatric disorder
• Catastrophization and fear avoidance behavior
• Coexisting chronic pain complaints
• High baseline pain scores and disability
• Previous treatment failures
• Chronic escalating opioid use
• Secondary gain
• Previous spine surgery
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38. SEMI-INVASIVETECHNIQUES:
INJECTION, INTRADISCAL PROCEDURES
• Thermal intradiscal/annular techniques (intradiscal electrothermal
therapy): have mostly been abandoned because of relatively poor
outcomes
• Electrostimulation: not long-lasting (a relatively high adverse-event
occurrence rate of up to 34.3%, including infection, surgical site pain, dural
puncture, and equipment/system problems)
• Epidural injection therapy: long-term efficacy is still unknown
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39. PERCUTANEOUS INTRADISCAL PROCEDURES
• Thermal Annular Procedures (TAPs): Level I
• Intradiscal electrothermal therapy (IDET): Level III
• Radiofrequency thermal annuloplasty (TA) using percutaneous endoscopic discectomy/TA (PED/TA)
• discTrode: LevelV
• Nucleoplasty: Level II-3
• NP PRF: 56% had > 50% pain reduction 1 year after first treatment
• Autologous bone marrow concentrate injection
• Intradiscal DiscoGel® or Methylene Blue Injection
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Radiofrequency maintained the epidural space at a safe temperature during nucleo-annuloplasty

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48. L2 DRG STIMULATION
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Mehta V, Bouchareb Y, Ramaswamy S, Ahmad A, Wodehouse T, Haroon A. Metabolic Imaging of Pain Matrix Using 18 F Fluoro-
deoxyglucose Positron Emission Tomography/Computed Tomography for Patients Undergoing L2 Dorsal Root Ganglion Stimulation for
Low Back Pain. Neuromodulation. 2020 Feb;23(2):222-233. doi: 10.1111/ner.13095. PMID: 32103593.

49. HF SCS
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51. SURGICAL INTERVENTION INDICATIONS
• Failure of conservative treatments for at least two to three months
• Interference or loss of ability to do activities in daily life due to
progressive neurogenic claudication, which limits walking due to pain,
weakening of the muscles, paresthesia in the buttocks or lower
extremities
• Rapidly progressing nerve impairment
• The presence of cauda equina syndrome
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52. INVASIVETECHNIQUES
• Discectomy
• Spinal fusion
• Total disc replacement (has less of a risk of ASD compared with fusion
surgeries). TDR is best indicated in spinal levels (eg, cervical) where maintained
mobility is of greater importance (Risk of heterotopic ossification and
reoperation)
• Percutaneous endoscopic or minimally invasive tubular decompressive surgeries
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54. FUTURETREATMENTS
• Restorative therapy entails molecular approaches, such as gene, growth
factor and cell therapy
• Precision medicine, particularly personalized biomaterial-based tissue
engineering tailored to the severity of disc degeneration
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55. REGENERATIVE MEDICINE
• Regenerative medicine strategies are considered most promising for early IVD
degeneration, where there is still the possibility to promote repair and healing
of the IVD.
• At present, the clinical application of regenerative medicine strategies is limited
to mesenchymal stem cell (MSC)/ bone marrow aspirate, platelet-rich plasma
(PRP), and chondrocytes.
• Experimental studies demonstrated cell leakage following injection with
ectopic calcifications as a potential complication, thus motivating the need for a
cell carrier to help enhance cell injections.
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56. STEM CELLTHERAPIES
• Multipotent mesenchymal stem cell (MSC) therapy (mitigation of primary nociceptive disc
pain, slow or reversal of the catabolic metabolism, and restoration of disc tissue): no effect on
recovering disc height
• Embryonic stem cells (ESCs) can differentiate into cells of all three germ layers in vitro
(ethical concerns, potential for immune rejection after transplantation, disease, and teratoma
formation)
Urits I, Capuco A, Sharma M, Kaye AD, Viswanath O, Cornett EM, Orhurhu V. Stem Cell Therapies for Treatment of
Discogenic Low Back Pain: a Comprehensive Review. Curr Pain Headache Rep. 2019 Jul 29;23(9):65. doi:
10.1007/s11916-019-0804-y. PMID: 31359164.
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57. IVD REPAIR TECHNIQUES:
TRANSPLANTATION OF THE NUCLEUS PULPOSUS
• Autologous nucleus pulposus cell re-implantation ? (improvements in LBP score, retention of
hydration in IVD, and increased disc height)
• Nucleus Pulposus Allograft (intact nucleus pulposus is more effective than injection of nucleus
pulposus cells alone)
• FibroblastTransplantation (taken from the rabbit skin)
Risk of Reherniation!
Nomura T, Mochida J, Okuma M, Nishimura K, Sakabe K. Nucleus pulposus allograft retards intervertebral disc degeneration. Clin Orthop Relat Res. 2001 Aug;(389):94-101. doi: 10.1097/00003086-200108000-00015. PMID:
11501830.
Ural IH, Alptekin K, Ketenci A, Solakoglu S, Alpak H, Özyalçın S. Fibroblast Transplantation Results to the Degenerated Rabbit Lumbar Intervertebral Discs. Open Orthop J. 2017 May 17;11:404-416. doi:
10.2174/1874325001711010404. PMID: 28603572; PMCID: PMC5447923.
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58. SOME ANNULAR CLOSURE DEVICES
AND NP REPLACEMENT DEVICES
• Barricaid (IntrinsicTherapeutics,Woburn, MA, USA)
• Xclose Tissue Repair System (AnulexTechnologies, Minnetonka, MN)
• Inclose Surgical Mesh System (AnulexTechnologies, Inc., Minnetonka, MN)
• NuCore® Injectable Nucleus hydrogel (SpineWave, Inc., Shelton, CT, USA)
• NeuDIsc (Replication Medical, Inc., Cranberry, NJ)
• DiscCell (Gentis,Wayne, Pennsylvania)
• DASCOR Disc Arthroplasty System (Disc Dynamics, Inc., Eden Prairie, Minnesota)
• BioDisc (CryoLife,Atlanta, Georgia)
• NucleoFix (Replication Medical, Inc., Cranberry, NJ)
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59. WHOLE IVD TISSUE-ENGINEERING STRATEGIES
• Considered as an alternative to
spinal fusion
• Reduced herniation risk
• Promoted integration with the
vertebral endplate
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60. EXOSOME-MEDIATED REPAIR
• MSC-derived miRNAs in exosomes and vesicles have therapeutic effects on
nucleus pulposus cells, annulus fibrosus, and cartilage endplate.
• miRNAs play a role in many cell activities, such as cell proliferation, apoptosis,
and cytokine release, by acting on mRNA translation.
• They may have immense therapeutic potential, especially when combined with
stem cell therapy.
Wang H, Lin S, Yu H. Exosome-mediated repair of intervertebral disc degeneration: The potential role of miRNAs. Curr Stem Cell
Res Ther. 2023 May 4. doi: 10.2174/1574888X18666230504094233. Epub ahead of print. PMID: 37150986.
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68. Thanks for your attention
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