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. 2020 Oct 9;16:953–968. doi: 10.2147/TCRM.S251495

The Technique of Intradiscal Injection: A Narrative Review

Alberto Migliore 1, Andrea Sorbino 2,✉, Serenella Bacciu 2, Alberto Bellelli 3, Bruno Frediani 4, Sandro Tormenta 3, Carmelo Pirri 2, Calogero Foti 2
PMCID: PMC7553660  PMID: 33116545

Abstract

Background

Low back pain (LBP) is one of the most common spine diseases and represents the most frequent cause of absence from work in developed countries. Approximately 40% of chronic LBP is related to discogenic origin. The goal of the study is producing a review of literature to describe analytically the techniques of intradiscal injections.

Methods

PubMed database was searched for clinical studies with the different key terms: “intradiscal”, “injection”, “steroid” “procedures”, “techniques”, “CT”, “MRI”, “fluoroscopy”, “fluoroscopic”, “guidance”, “ozone”, “ultrasound”, “images”. Only studies written in English, French, or Italian in which the intradiscal injection represents the main procedure for the low back discopathy treatment on humans were considered. We excluded the articles that do not mention this procedure; those which indicated that the intradiscal injection had happened accidentally during other treatments; those reporting the patient’s pain was determined by other causes than the discopathy (facet joint syndrome, tumor, spondylodiscitis).

Results

Thirty-one articles dated from 1969 to 2018 met the criteria. The examined population was 6843 subjects, 52.3% male and 47.7% female, with a mean age of 45.9±10.1 years. The techniques are highly variable in terms of procedure: different operators, needle guidance, injection sites, drugs, tilt angle of the needle).

Conclusion

The efficacy and the safety of the intradiscal procedures are not easily comparable due to different types of studies and their limited number. Further studies are needed to standardize the intradiscal injection technique/procedure to improve safety, repeatability and effectiveness, and last but not least to reduce peri- and postoperative care and health-care costs.

Keywords: discopathy, guidance, injection, intradiscal injections, low back pain, safety

Background

Low Back Pain (LBP) is one of the most common spine diseases and represents the most frequent reason of absence from work in developed countries. Around 80% of adults suffer from LBP during their lifetime, and 55% suffer from back pain associated with radicular syndrome.1 Chronic LBP is often responsible for a low quality of life due to pain, for disability and loss of work productivity and, in addition, for high health-care costs for society.2–4 Regarding its etiology, in literature it has been reported that approximately 40% of chronic LBP has a discogenic origin.5,6 Currently in the advanced phases of discopathy and in high symptomatic subjects, the elective treatment still remains spinal surgery. In the other less complicated cases, the therapeutical steps could vary from a simple pharmacological therapy to a physical therapy, as the low back traction, over to spinal injection (epidural, periradicular, intradiscal and intra-articular procedures). Moreover, intervertebral disk decompression techniques are minimally invasive outpatient procedures for the treatment of disk herniation. Under imaging guidance and via a percutaneous approach, a needle is inserted in the nucleus pulposus of the herniated disk. A variety of decompressive device of thermic, chemical or mechanical nature are introduced inside the nucleus pulpous with minimal disruption of the surrounding tissues, assuring its partial removal and a significant decrease of intradiscal pressure. Thermal decompression is achieved using laser fiber, plasma, energy electrode, and radiofrequency coil/electrode. Chemical decompression is achieved by alcohol gel or ozone intradiscal injection, which causes dehydration and breakdown of the nucleus pulposus. Lately, there has been a trend for biomaterial implantation (hydrogel, platelet-rich plasma and stem cell therapy) aiming for intervertebral disk regeneration. Symptomatic intervertebral disk herniation (refractory to 4–6 weeks of a conservative therapy course), occupying less than one third of the spinal canal, as confirmed by MRI (magnetic resonance imaging), is an indication for percutaneous decompressive disk therapies. The mean success rate for all techniques is approximately 85%. The mean complication rate (infections like spondylodiscitis, allergic reaction, hemorrhage, neurologic injury) is <0.5%.7 The goal of the study is producing a review of literature to describe analytically the actual techniques of intradiscal injections, the type of intervention performed, the used imaging guidance, the inoculated drug, the approach to the intervertebral disc, the patient’s position, the specialty of the operator performing the procedure, the type of anesthesia and the use of antibiotic prophylaxis.

Methods

Search Strategy

The PubMed database was searched for clinical studies with the following key terms: “intradiscal”, “injection”, “steroid” “procedures”, “techniques”, “CT” (computerized tomography), “MRI”, “fluoroscopy”, “fluoroscopic”, “guidance”, “ozone”, “ultrasound”, “images”. We made our research throw the combination of this terms, inserted between the Boolean operators “AND”/“OR”. We limited the research to studies on humans and types of articles were: case reports, clinical trials, controlled clinical trials, reviews, comparative studies, multicenter studies, and randomized controlled trials. The search was expanded through the bibliography within recruited texts (Figure 1).

Figure 1.

Figure 1

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Flow diagram illustrating published literature on intradiscal injection.

Inclusion and Exclusion Criteria

For our review, we only considered studies written in English, French, or Italian in which the intradiscal injection represents the main procedure for the low back discopathy treatment, both isolated and in combination. We excluded the articles that did not mention that procedure or those which indicated that the intradiscal injection had happened accidentally during other treatments (ie during transforaminal injection). We excluded the articles where the patient’s pain was due to other causes than the discopathy (facet joint syndrome, tumor, spondylodiscitis), and also those articles that described the treatment performed on an animal species. We checked the bibliography to make sure that the articles were compatible with our research.

Results

Initially using the term “intradiscal injection” as a search key on PubMed, we found 385 articles; the results were reduced when we added other search keys or other selection criteria, as we showed in the description of our strategy of research. Depending on the abstracts or full texts we excluded the studies that did not satisfy the inclusion criteria. Moreover, in this review we included other articles shown as bibliography in previous research. The final result consisted of 31 articles4,8-26,35–44 dated from 1969 to 2018, and the examined population was 6843 subjects (Table 1). We did not consider the number of patients treated in the Giurazza et al study38,40 because being a review, it considered not only intradiscal, but also paravertebral injections. We also decided to cite other authors that described the varied and numerous procedures that are available to the image-guided interventions who may provide these therapies for the spine.27–31

Table 1.

Clinical Characteristics of Trials Employment of Intradiscal Injection

Authors, Date Study Design Population End Points Disease Treated Intervention Medicament Guidance Approach Outcomes Results Follow-up Adverse Events
Kallewaard et al4 2015 Multicenter pilot study 174 Efficacy and safety of the treatment LBP ID Blue methylene Fluor ND VAS, ODI, SF-36, PGIC Pain relief in 40% of patients 24 weeks No
Mineta et al8 2014 Case report 1 Association Modic type I-inflammation LBP ID Cs ND ND VAS and Modic change Modic type switch depends on inflammation ND ND
Zhang et al10 2013 Case–control 172 Comparison between 2 groups of the treatments LBP ID/IF Ozone Fluor PL VAS, JOA score Significant pain relief in both groups 3, 24, 48 weeks No
ID/IF Ozone Cs Differences between treatments No statistically significant differences
Beaudreuil et al11 2012 Observational Retrospective study 97 Efficacy in (EG) compared to (C) LBP±Modic ID Cs Fluor ND VAS and self-assessed of pain Significant pain decrease in EG compared to CG 24 h, 48–56 weeks No
Lehnert et al12 2012 Observational prospective study 283 Efficacy of the treatment LBP ID Ozone CT EL Disk volume reduction evaluated with CT Decrease in 91.1% of patients and increased in 3.9% of patients 24 weeks Impaired sensitivity lower limb 24 cases
PG
de Seze et al13 2012 Observational prospective study 79 Efficacy and safety of the treatment LBP ID Discogel Fluor PL Verbally numeric scale (from 0 to 10) Free pain in 60.7% of patients 8, 24 weeks No
Fukui et al14 2012 Observational prospective study 45 Comparison of effectiveness between 2 treatment ID Saline sol LA Fluor PO VAS, JOA score Pain improvement for IDHP compared to MED 2, 12 weeks No
MED /
Yu et al15 2012 Case–control study 45 Comparison of effectiveness between 2 treatment LBP ID Cs CT ND VAS, ODI Improvement of pain in the EC compared to CG 1, 4, 12, 24 weeks ND
Saline sol
Cao et al16 2011 RCT 120 Comparison of effectiveness between 2 treatment LBP ID Cs ± Songmeile CT PL VAS, ODI Significant pain improvement in the EC compared to CG 12, 24 weeks ND
Saline sol
Muto et al17 2008 Observational
Retrospective study		 2900 Efficacy and safety of the treatment Lumbar disk herniation ID/PG/PR Ozone CT PvO VAS, ODI Significant pain decrease in 85% of cases 24, 48 weeeks No
Oder et al18 2007 Observational Prospective study 621 Efficacy of treatment in different groups LBP ID/PG/Ep Ozone, Cs, LA CT+ Fluor Post VAS Significant pain improvement in 59.4% of all patients 24 weeks No
Fayad et al19 2007 Pilot study 74 Comparison of effectiveness between Modic type Groups LBP + Modic ID Cs Fluor PL VAS, PGA Significant pain improvement ModicI >Modic I-2 > ModicII-1 4, 12, 24 weeks No
Gallucci et al20 2007 RCT 159 Comparison of effectiveness between 2 groups LBP disk herniation ID/IF Cs + LA CT Pv Oswestry Low Back Pain Disability Questionnaire Significant pain decrease for 47% in group A, 74% in group B 24 weeks No
ID/IF Cs, LA, ozone IL
Miller et al21 2006 Prospective study 76 Efficacy of the treatment LBP + leg pain ID HyD LA Fluor ND Numeric pain score scale Pain improvement in 43.4% of patients 6, 164 weeks ND
Benyahya et al22 2004 Observational retrospective study 85 Efficacy/safety of the treatment LBP Modic ID Cs CT PL Global appreciation “good or excellent” of the patient in % 71.8% at 1 month 55.3% at 3 months 43.5% at 6 months 4, 12.24 weeks Collapse 2 discs
Khot et al23 2004 RCT 120 Comparison of effectiveness between 2 groups LBP ID Cs Fluor PL VAS, ODI No improvement in experimental group compared with placebo 48 eeks No
Saline sol
Andreula et al24 2002 Multicenter study 600 Comparison of effectiveness between 2 groups LBP ID/PG Ozone + O3 Fluor EL Modified MacNab method Successful of the treatment in 70.3% group A 78.3% group B 24 eeks Impaired sensitivity lower limb 2 cases
ID/PG Ozone, Cs, LA CT
Feffer et al25 1969 Observational prospective study 244 Efficacy of the treatment LBP ID Cs Fluor PL Back pain (yes/no), radicular pain (yes/no) Complete remission in 46.7% of patients; “no initial response” in 53.3% of patients. 4–10 years Discitis 1 case
Pettine et al35 2017 Observational prospective study 26 Efficacy of the treatment LPB ID AT-BMC Flour PL VAS, ODI VAS: 82.1 (±2.6) at baseline and 21.9±4.4 at 3 Y. ODI: 56.7 (±3.6) at baseline and 17.5±3.2 at 3 years. 3 years No. Only 6 patients had progression to surgery
Yin et al9 2014 Multicenter study 15 Efficacy and safety of the treatment LBP ID FS Flour PL VAS, RMDQ, Rx/MRI VAS 72.4, 31.7, 35.4, 33 at baseline, 26, 52, 104 weeks. (significant improvement) RMDQ 15.2, 8.9, 6.2; 5.6 at baseline, 26, 52, 104 weeks. Rx/MRI similar to baseline 104 weeks Low back muscle spasm 2 cases. Discitis 1 case
Sainoh et al36 2016 Prospective randomized study 60 Efficacy of the treatment LBP ID TNF-α I Flour PL VAS, ODI Significant pain improvement in 57% of all patients at 8 weeks in patient treated with TNF-α I. No significant difference about ODI 8 weeks Not
Noriega et al44 2017 Randomized, controlled trial 24 Efficacy and safety of the treatment LBP Nd Nd Nd ND VAS, ODI, SF-12 Average 28% improvement in pain and disability 1 year after the intervention 1 year ND
Giurazza et al38 2017 Review ND Efficacy and safety of the treatment LBP ID Oz Flour; CT PL, Pv/IL, TF VAS, ODI Improvement in pain and disability Up to 10 years 0.1% Paraesthesias; temporary impaired bilateral sensitivity; vitreoretinal hemorrhages; thunderclap headache 1 case of vertebrobasilar stroke 1 case of septicemia
Pettine et al42 2015 Observational prospective study 26 Efficacy and safety of the treatment LBP ID AT- BMC Flour PL VAS, ODI (71% VAS reduction) and ODI improvements (>64%) through 2 years. 2 years No. only 5 patients had progression to surgery
Nguyen et al34 2017 Prospective, parallel-group, double-blind, randomized, controlled, multicenter study. 135 Efficacy and safety of the treatment LBP ID Cs Flour PL VAS, MRI at 12 months The percentage of responders (LBP intensity <40) at 1 month was higher in the GC IDI group in than the control group; At 12 months, the groups did not differ in pain intensity or most other secondary outcomes. No difference at MRI 1 year 1 event increase in sciatica pain in the 24 h after the intervention
Perri et al41 2016 Observational prospective study 517 Efficacy and safety of the treatment LBP ID Oz+Cs+LAVs Cs+LA CT P VAS The study group had a successful outcome in 80% of patients after 6 months, while the control group had a successful outcome in 31.5% 6 months Not
Zhang et al37 2016 Observational study 33 Efficacy and safety of the treatment LBP ID BM Flour PL NRS, ODI, MRI (apparent diffusion coefficient in T2) Significant improvement at short-term minimum of 2 points reduction of rating scale scores at 1, 3, and 6 months after treatment, but less than 2 points reduction at 12 months; 50% improvement on the ODI at 1, 3, and 6 months after treatment, but not at 12 months. Apparent diffusion coefficient and T2 value were significantly higher at 6 and12 months after treatment, but no difference at 3 months. 12 months Not
Levi et al46 2016 Prospective study 22 Efficacy and safety of the treatment Discogenic LBP ID PRP Flour PL VAS, ODI Significant improvement 6 months Not
Tuakli-Wosornu et al39 2016 Prospective, double-blind, randomized controlled study. 47 Efficacy and safety of the treatment Discogenic LBP ID PRP Flour PL NRS, FRI, SF-36, NASS Significant improvement 1 year Not
Kumar41 2017 Single-arm phase I clinical trial 10 Efficacy and safety of the treatment LBP ID AT-MSC Flour PL VAS, ODI, SF-36, MR-ADC Significant improvement; 3 patients increased water content based on the ADC map at the 12-month follow-up 1 year Not
Centeno et al43 2017 Pilot study 33 Efficacy and safety of the treatment LBP ID AT-MSC, LA Flour PL NRS, SANE, FRI, MIDPD Significant improvement; the patients treated underwent post treatment MRI and 85% had a reduction in disc bulge size, with an average reduction size of 23% post
-treatment		 6 years Not
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Abbreviations: ADC, apparent diffusion coefficient; AL-MSC, allogenic mesenchymal stem cells; AL, anterolateral; AT-BMC, autologous bone marrow concentrate; AT-MSC, adipose tissue mesenchymal stem cells; BM, blue methylene; C, control group; Cs, corticosteroid; EG, experimental group; EL, extraspinal lateral; Ep, epidural; EQ-5, EuroQol; Fluo, fluoroscopy; FRI, Functional Rating Index; FS, fibrin sealant; HA, hyaluronic acid; HyD, hypertonic dextrose; ID, intradiscal injection; LA, local anesthetic; LBP, low back pain; MGPQ, McGill Pain Questionnaire; MIDPD, measurement of the intervertebral disc posterior dimension; MSC, mesenchymal stem cells; NASS, the modified North American Spine Society; ND, not described; NRS, Numeric Rating Scale; ODI, Oswestry Disability Index; P, pain; PG, periganglionic injection; PL, posterolateral; PO, posterior-oblique; Post, posterior; PR, periradicular injection; PRP, platelet-rich plasma; Pv/IL, paravertebral/interlaminar; PvO, paravertebral-oblique; RCT, randomized controlled trial; RMDQ, Roland–Morris Disability Questionnaire; SANE, modified single assessment numeric evaluation; SF-36, short form-36; SNRB, selective nerve block; TF, transforaminal; TNF-α I, tumor nerosis factoralpha inhibitor; VAS, visual analog scale;.

Characteristics of Included Articles (Table 1)

The review includes three observational retrospective studies,12,18,23 12 observational prospective studies,13–15,19,22,26,36-38,41,43,44 two multicenter pilot studies,4,10 two case–control studies,11,16 six randomized controlled trials,4,8,17,21,24,35,42 one multicenter study25 two pilot studies,20,43 one case report,9 one single arm phase I clinical trial44 and one review.40

Population

Our population is composed of 6843 subjects, 52.3% male and 47.7% female, with a mean age of 45.9±10.1 years.

End Points

The aim of the study was to review literature for scientific evidence of intradiscal injections, to describe analytically the actual techniques, the type of intervention performed, the used imaging guidance, the inoculated drug, the approach to the intervertebral disc, the patient’s position, the operator who performed the treatment, the type of anesthesia used, antibiotic prophylaxis, if used.

Treated Disease

In all selected articles,4,9-26,35–38,39–44 the patients suffered from lumbar discopathy.

Type of Procedure

Different types of treatments are reported in the studies: intradiscal injection,4,8-26,35–44 epidural19 intraforaminal11,21 and facet joint injection, selective nerve block (SNRB),8 intradiscal high pressure injection (IDHP),15 microendoscopic discectomy (MED).16

Intradiscal Injection

The technique of intradiscal injection is reported in 31 articles. In 24 studies,4,9,10,12,14,16,17,20,22-24,26,35–44 it is the only treatment while, in the remaining seven studies11,13,15,18,19,21,25 it is compared to, or in association with, other minimally invasive procedures. (Table 2). In 19 articles the procedure was realized under fluoroscopy,4,10-12,14,15,20,22,24,26,35–39,41,42,44 in seven articles under CT guide,13,16–18,21,23,43 and in three studies both by fluoroscopy and CT guided, in comparison25 or in association;19,40 in two articles was not specified9,44 (Figure 2).

Table 2.

Characteristics of Intradiscal Injection Techniques

Authors Intervention Drugs Guidance C-Arm Approach Needle Injection Site Injection Check Operator Patients Position Sedation Local Anesthesia Antib Prophilax Rest After Injection
Kallewaard et al4 ID BM, LA Fluor No ND ND ND AP/L ND ND ND ND Yes 2 h
Mineta et al8 ID Cs ND No ND ND ND ND ND ND ND ND ND ND
Yin et al9 ID FS Fluor No PL 18G CTh RTMF ND ND No Yes Yes 1, 1/2 h
Zhang et al10,11 ID/IF Oz Fluor Yes PL 21G C AP/L ND * No Yes ND 10 min
ID/IF Oz Cs
Beaudreuil et al11 ID Cs Fluor No ND ND C ND ND ND No Yes ND 12/24 h
Lehnert et al12 ID Oz CT No EL 22G ND ND ND ND Nt Yes ND 6 h
PG
De Seze et al13 ID Discogel Fluor No PL 22G C AP/L ND ND DS No ND 3 h
Fukui et al14 ID Saline sol, LA Fluor No PO 22G MPHD AP/O/L ND P ND ND ND 1 h
Yu et al15 ID Cs CT No ND ND ND ND ND ND ND ND ND ND
Saline sol
Cao et al16 ID Cs, Songmeile CT No PL 22G C ND Authors ND ND ND ND 3 h
Saline sol
Muto et al17 ID/PG/PR Oz CT No PvO 18/20G C ND ND P ND ND ND ND
Oder et al18 ID/PG/Ep Cs, LA, Oz CT/Fluor No Post 22G C CT scan ND P Yes Yes Yes 12 h
Fayad et al19 ID Cs Fluor No PL 22G C AP/L Radiol ND No No ND ND
Gallucci et al20 ID/IF Cs, LA CT No Pv/IL 22G C CT scan NeuroR P No Yes Yes 2 h
ID/IF Cs, LA, Oz
Miller et al21 ID HyD, LA Fluor No ND 22G C ND ND ND ND ND ND ND
Benyahya et al22 ID Cs CT No PL ND C ND Radiol ND ND ND ND ND
Khot et al23 ID Cs Fluor No PL ND ND ND Authors ND AwS No ND ND
Andreula et al24 ID/PG Oz, O3 Fluor No EL 22G ND ND ND ND No No ND 2 h
ID/PG Oz, Cs, LA CT
Feffer et al25 ID Cs Fluor No PL 22G ND ND ND ND ND ND ND ND
Centeno et al43 Ep/ID AT-MSC, LA Fluor No PL ND ND ND ND P No Yes ND ND
Zhang et al37 ID BM Fluor Yes PL ND C Dis ND P ND ND ND 24 h
Tuakli-Wosornu et al39 ID Prp Fluor ND PL 20G/25 G C Dis Physiatrist P No Yes Yes ND
Kumar et al41 ID AT-MSC, HA Fluor Yes PL 22 G C CT scan Spine surgeon P ND Yes Yes 4 h
Levi et al46 ID Prp Fluor ND PL 22G/25 G C ND Physiatrist P Yes Yes Yes ND
Pettine et al35 ID AT-BMC Fluor ND PL 22G C ND ND P No Yes ND ND
Sainoh et al36 ID TNF-α I Fluor ND PL 22 G C RTMF ND LD No Yes ND ND
Noriega et al44 ND AL-MSC ND ND ND ND ND ND Radiologists ND ND Yes ND ND
Giurazza et al38 ID O2-O3 Fluor, CT ND PL, Pv/IL, TF 18–22 G C ND Radiologists P Yes ND ND ND
Pettine et al42 ID AT-BMC Fluor NDd PL 22 G C ND ND P No Yes No ND
Nguyen et al34 ID Cs Fluor ND PL 18/22 G C ND Radiologists LD No No No ND
Perri et al40 ID O2-O3 CT ND Pv/IL 22 G C CT Neuroradiologists P No Yes Yes ND
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Note: *A pillow was placed under the waist of patients.

Abbreviations: AL- MSC, allogenic mesenchymal stem cells; AL, anterolateral; AT-BMC, autologous bone marrow concentrate; AT-MSC, adipose tissue mesenchymal stem cells; Aw S, awake sedation; BM, blue methylene; C, center of the disc; Cs, corticosteroid; CTh, central third of the disc; Dis, discography; DP, deep sedation; EL, extraspinal lateral; Ep, epidural; Fluor, fluoroscopy; FS, fibrin sealant; G, gauge; h, hours; HA, hyaluronic acid; HyD, hypertonic dextrose; ID, intradiscal injection; IDHP, intradiscal high pressure injection; L, lateral; LA, local anesthesia; LD, lateral decubitus; MED, microendoscopic discectomy; min, minutes; MPHD, mid portion of herniated disc; MSC, mesenchymal stem cells; ND, not described; NeuroR, neuroradiologists; Oz, ozone; P, prone; PG, periganglionic injection; PL, posterolateral; PO, posterior-oblique; PR, periradicular injection; Prp, platelet-rich plasma; Pv/IL, paravertebral/interlaminar; PvO, paravertebral-oblique; Radiol, radiologists; RTMF, real-time multiplanar fluoroscopic imaging; SNRB, selective nerve block; Songm, Songmelie; TF, transforaminal; TNF-α I, tumor nerosis factor-α.

Figure 2.

Figure 2

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Different type of image guidance for intradiscal injection.

The patients of the de Seze et al trial,13 Levi et al46 and Giurazza et al38 works were subjected to neurosedation, in the trials by Khot et al23 and Oder et al18 they were subjected to conscious sedation. In the studies by Fayad et al19 and Andreula et al24 and another five works34,37–39 the patients were neither sedated nor subjected to local anesthesia. In eleven trials,10,11,13,19,21,36,37,41–44 all patients were subjected to local anesthesia. The antibiotic prophylaxis was used in eight trials.4,10,19,21,41–44 The interventions were performed by highly experienced operators in the Lehnert’s trial12 two clinicians (two authors) in the Cao et al’s study;16 Fayad et al,19 Benyahya et al,22 Noriega et al,44 Giurazza et al,38 and Nguyen et al34 report the experienced radiologists, Gallucci et al20 and Perri et al40 neuroradiologists, Tuakli-Wosornu et al39 and Levi40,46 physiatrist and Khot et al23 two senior authors.

In 17 articles the required patients position was described according to the procedure: in 11 studies a prone position was used,15,18,19,21,36,38,40–44 Nguyen et al34 and Sainoh et al36 propose a lateral decubitus and Zhang et al10 advised use of a pillow under the waist to get the widest intervertebral spaces.

For the procedure spinal needles of 18- (n=4), 20- (n=2), 21- (n=1), 22- (n=17) and 23- (n=1) gauge were used, with variable length to 7 from 17.8 cm. For example the Muto et al’s study17 mentioned a 22-gauge spinal needle with paravertebral oblique access, Lehnert et al’s study12 mentioned an extraspinal lateral approach with a 22-gauge 17.8-cm spinal needle and Gallucci et al20 a paravertebral/interlaminar approach with a 9- or 15-cm 22-gauge spinal needle Five articles13,14,21,22,25 have specified that the side of the injection was chosen on the basis of the main location of symptoms.

The percutaneous approach is always posterior for the lumbar access: in 15.10,11,14,17,20,23,24,26,35,36,38,40–44 out of 31 articles it was specified as a posterolateral access, in other studies it was extralaminar12 or paravertebral access,20 posterior-oblique14 paravertebral-oblique,17 or anterolateral access. In the Gallucci et al’s study20 the intradiscal and intraforaminal injections were administered with a paravertebral approach in 92.4% of the patients and an interlaminar approach in 7.6% of the patients. The needle was advanced through the intraforaminal space, with an angle usually between 45° and 60°. In seven articles the point of access is not described.4,9,12,16,22,39,44 Oder et al’s study18 specified that the percutaneous approach was about 45° along the lateral margin of the inferior articular process of the vertebra and through the neuroforamen for preserving the nerve root. Muto et al17 used a needle inclination in a craniocaudal direction in the case of a lower herniation.

The site of injection is the center of the disc in 22 studies,7,10,11,13,16-22,35–44 the central third of the disc in the Yin et al’s study9 and in the mid portion of the herniated disc in the Fukui et al’s study.14 The position of the needle was confirmed by fluoroscopy using anteroposterior and lateral views in 20 studies;4,8,10–12,14,15,20,22,24,25,35–39,41,42,44 in Yin et al’s trial9 the procedures were performed with real time multiplanar fluoroscopy, with CT scan in seven other articles,13,16–18,21,23,43 in three articles with both fluoroscopy and CT,19,25,40 in two articles the position of the needle is not described.9,40

Some authors recommend the time remaining in supine position after injection: respectively 10 minutes;10 one hour,14 one, half an hour,9 two hours,4,21,25,39 three hours,13,16 four hours,41 six hours;12 12 h,18 12/24 h.11,37

Medicaments Injected

Several drugs have been injected, and were used individually or in association with each other: an oxygen-ozone mixture (O2O3) in eight studies,10,12,17,18,20,24,38,40 a saline solution in four studies;14–16,23 in 13 articles the steroids have been administered (methylprednisolone, acetate of prednisolone, hydrocortisone, betamethasone),8,10,11,15,16,18–20,22–25,34 and in six trials the local anesthetic (bupivacaine, lidocaine) were injected.4,14,20,21,24 For the remaining studies hypertonic dextrose,21 fibrin sealant,9 blue methylene,4,37 discogel,13 autologous bone marrow concentrate,35,42 allogenic mesenchymal stem cell and hyaluronic acid,41 tumour necrosis factor α1 inhibitor36 and songmeile16 (a kind of synthetic liquid of polypeptidic biological factors extracted from Chinese herbal medical ingredient) were used.

Outcomes Measures

Pain was the most frequently tested variable. It was expressed as percentage of patients with pain relief or as mean improvement on a continuous scale. The outcome measures shown in the studies were: VAS (visual analog score), NRS (numeric rating scale), McGill Pain Questionnaire. Outcome assessment of patient satisfaction are reported by “modified MacNab scale” or using Odom criteria (“Excellent”, “Good”, “Satisfactory” and “Poor”). Back-specific disability is expressed on a back-specific index, such as the Roland Disability Questionnaire or the Oswestry Disability Index and JOA score (widely used in Japan to evaluate disabilities associated with low-back pain and includes the following items: subjective symptoms; clinical signs; restriction of activities of daily living. JOA score ranges from 29 as the most positive score to minus six for the worst a global measure of improvement). Quality of life is measured by the SF-12, SF-36, and EuroQol.

Patients Global Impression of Change (PGIC) measured by a seven-point Likert scale. The evaluations of general health status or well being, disability for work, and patient satisfaction have all so been reported.

The disc volume was evaluated by MRI and CT images.

Clinical and/or radiologic short term follow-up were mainly performed at four or six weeks; the long-term follow-up were performed from 12, 24, 48, weeks up to 4–10 years.

Efficacy

The efficacy of the treatment is the target in 30 articles,4,9–25,34–44 The results are reported as clearly satisfactory in 27 out of the 30 articles,4,9–20,22,24,34–44 In the Muto et al’s study, for example, the results on 2900 patients, treated for LBP with intradiscal injection of O2–O3, were evaluated with the modified MacNab classification, the VAS and the Oswestry Disability Index at six and 12 months. Success rates were 75–80% for soft disc herniation, 70% for multiple-disc herniations and 55% for failed back surgery syndrome. None of the patients suffered early or late neurological or infectious complications.17 Benyahya et al22 made a retrospective study of medical records of 85 patients (55 women, mean age 49±9 years) to assess the effectiveness of intradiscal injection of acetate of prednisolone for the treatment of LBP. They used the global appreciation of the patient (excellent, good, mild, none, worse) concerning the result of the intradiscal injection, at one, three and six months. For effectiveness of intradiscal injection, the results showed that 71.8% of the patients considered the result good or excellent at one month, 55.3% at three months and 43.5% at six months.

Adverse Events

Six trials have reported the side effects,9,12,22,24,26,34 overall 32 cases for 6843 patients (0.47% of patients): three cases of discitis, two after injection of corticosteroid,25 one after injection of fibrin sealant;9 26 patients present impairment of sensitivity in the lower limb ipsilateral to the treatment with injection oxygen-ozone;12,24 two discs showed a collapse after injection of corticosteroid,22 1 case of increase in sciatica pain in the 24 hafter the intervention.34

Two trials were performed under CT guidance;12,22 two studies were performed by fluoroscopy,9,25 and only one case by both fluoroscopy and CT guide.24 Adverse events occurred in about 0.7% of the patients with CT guided injection and in 0.2% of the patients with fluoroscopic guided injection. In Yin et al’s trials,9 the patients have even been subjected to antibiotic prophylaxis, in others articles this was not described.

Yin et al, Lehnert et al, Benyahya et al, Andreula et al and Feffer et al9,12,22,24,25 report a posterolateral/extraspinal-lateral approach. Giurazza et al report that

The overall procedural complications rate is estimated around 0.1%. Have been reported in the literature: paresthesia on the anterolateral portion of the left leg and foot, suggesting nerve injury; few temporary episodes of impaired bilateral sensitivity; vitreoretinal hemorrhages; thunderclap headache related to pneumoencephalus as a consequence of inadvertent intrathecal puncture; and 1 case of vertebrobasilar stroke.38

Discussion

For the low back pain management, patients with a small or contained herniated disc with no response to medical treatments, can be candidates for one of the minimally invasive percutaneous techniques. Generally, the minimally invasive techniques offer good results with patient compliance and low cost, showing a very low side effects percentage.20 Only 0.47% of patients have manifested adverse events after intradiscal injection. The procedure is carried out on an outpatient basis by highly experienced operators such as radiologists,19,22 neuroradiologists,20 physiatrists46,39 and orthopedics.23 The procedure is of interest for many medical areas, for this reason standardizing this method allows it to be extended to various practitioners.

For preoperative management there is no consensus regarding sedation, local anesthesia, or antibiotic prophylaxis. Only seven authors mention antibiotic use,4,9,20,46–41 only two articles describe conscious sedation18,23 and three describe a deep sedation.13,38,46 Some unreviewed medical articles28,29 do not recommend local or general anesthesia because they could mask the nerve root puncture symptoms; the needle passes very close to the nerve root and may often touch it, causing a strong electric shock sensation which is quite harmless; if the patient is conscious they will feel the pain. About 0.19% of the patients subjected to antibiotic prophylaxis have had adverse events; while without antibiotics about 0.09% of the population have had side effects; current data do not allow a statistical analysis; for this reason prospective clinical trials are needed. Some authors advise setting up an aseptic room for anesthesiology care, ensuring peripheral access to the patient.29

A concordance has emerged about the patient position, the injection site and the needle type. The most included articles14,17,20,26,28–30,35,37-44 report a prone position as the best to increase the intervertebral space, also using a support under the abdomen to reduce lumbar lordosis. The lateral decubitus was reported in two works34,36 and in an unreviewed journal on chemiodiscolysis with ozone.28 According to five of the articles,12,13,20,21,24 de Santis et al29 recommend an access side at the same side as the symptoms.

The chosen injection site is the center of the disc, and the injection point was checked by fluoroscopic projections,4,9–11,13,14,19,21,23,25,34–39,41,43 CT scans;12,15–18,20,23,24,38,40 we highlight the need for trials to evaluate the more effective, safe, and less expensive methods, especially if using a toxic or very expensive drugs. For the safety, the data do not clarify which is the least injurious method, even though we have recorded a greater percentage of adverse events with the CT guided injection (Table 1). Clinical trials with same medication comparing the fluoroscopy and CT guided injections are needed.

During the procedure, the needle can be readily shifted a few millimeters to pass through without damaging the nerve. The approach and the needle inclination are essential criteria for a successful and safe procedure. In some articles it appears that the lumbar approach has a lateral inclination of 45° to 60° with respect to the axial line18,20 and that for the lower discs an additional cranial-caudal inclination is needed.20 We did not find accurate descriptions on the needle insertion procedure because the needle course was always evaluated radiographically and the access site was chosen accordingly. The authors recommend and/or use a fluoroscopy performed with the C-arm, that allows identification the trajectory of optimal access for needle placement into each disc.10,29,30 An image-guided procedure handbook30 describes a window of anatomical access to the intradiscal injection delineated by the superior articular process medially, the superior endplate below, and the traversing nerve root laterally and above. Staying close to the superior articular process could keep the needle as far as possible from the traversing nerve root.

The postintervention management was different between treatments, the authors have advised several rest times depending on the procedure (Table 2).

The efficacy and the safety of the intradiscal procedures are not easily comparable because the techniques are highly variable in terms of procedure (different operators, needle guidance, injection sites, drugs, tilt angle of the needle) (Table 2).

Conclusions

The efficacy and the safety of the intradiscal procedures are not easily comparable because of differences in the design of studies and their limited number.

The intradiscal injection is a technique widely used in the LBP management of patients with no response to rehabilitative and medical treatments. Differences of agreement between researchers are present on the technical aspects of the procedure in terms of imaging guidance, of injected substances, and efficacy of evaluation tools.

Further studies are needed in order to standardize the intradiscal injection technique/procedure as well as to improve efficacy, safety, repeatability, and to assess cost-effectiveness.

Funding Statement

This work is not supported by funds.

Abbreviations

ADC, apparent diffusion coefficient; AL-MSC, allogenic mesenchymal stem cells; AT-BMC, autologous bone marrow concentrate; AT-MSC, adipose tissue mesenchymal stem cells; BM, blue methilene; C, control group; Cs, corticosteroid; CT, computerized tomography; EG, experimental group; EL, extraspinal lateral; Ep, epidural; EQ-5D, EuroQol; Fluor, fluoscopy; AL, anterolateral; FRI, Functional Rating Index; FS, fibrin sealant; HA, hyaluronic acid; HyD, hypertonic dextrose; ID, intradiscal injection; LA, local anesthetic; LBP, low back pain; MGPQ, McGill Pain Questionnaire; MIDPD, measurement of the intervertebral disc posterior dimension; MRI, magnetic resonance imaging; MSC, mesecnchymal stem cells; NASS, the modified North American Spine Society; NRS, Numeric Rating Scale; ODI, Oswestry Disability Index; P, periganglionic injection; PL, posterolateral; PO, posterior-oblique; Post, posterior; PR, periradicular injection; PRP, platelet-rich plasma; Pv/IL, paravertebral/interlaminar; PvO, paravertebral-Oblique; RCT, randomized controlled trial; RMDQ, Roland–Morris Disability Questionnaire; SANE, modified single assessment numeric evaluation; SF-36, short form-36; SNRB, selective nerve block; TF, transforaminal; TNF-α I, tumor nerosis factor α inhibitor; Treatm, treatment; VAS, visual analog scale.

Data Sharing Statement

All data analyzed during this study are included in this article.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no competing interests in this work.

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