The Technique of Intradiscal Injection: A Narrative Review

Figures & data

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 al^Citation4 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 al^Citation8 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 al^Citation10 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 al^Citation11 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 al^Citation12 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 al^Citation13 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 al^Citation14 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 al^Citation15 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 al^Citation16 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 al^Citation17 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 al^Citation18 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 al^Citation19 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 al^Citation20 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 al^Citation21 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 al^Citation22 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 al^Citation23 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 al^Citation24 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 al^Citation25 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 al^Citation35 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 al^Citation9 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 al^Citation36 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 al^Citation44 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 al^Citation38 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 al^Citation42 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 al^Citation34 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 al^Citation41 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 al^Citation37 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 al^Citation46 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 al^Citation39 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
Kumar^Citation41 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 al^Citation43 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

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;.

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 al^Citation4	ID	BM, LA	Fluor	No	ND	ND	ND	AP/L	ND		ND	ND	ND	Yes	2 h
Mineta et al^Citation8	ID	Cs	ND	No	ND	ND	ND	ND	ND		ND	ND	ND	ND	ND
Yin et al^Citation9	ID	FS	Fluor	No	PL	18G	CTh	RTMF	ND		ND	No	Yes	Yes	1, 1/2 h
Zhang et al^10,^Citation11	ID/IF	Oz	Fluor	Yes	PL	21G	C	AP/L	ND		*	No	Yes	ND	10 min
	ID/IF	Oz Cs
Beaudreuil et al^Citation11	ID	Cs	Fluor	No	ND	ND	C	ND	ND		ND	No	Yes	ND	12/24 h
Lehnert et al^Citation12	ID	Oz	CT	No	EL	22G	ND	ND	ND		ND	Nt	Yes	ND	6 h
	PG
De Seze et al^Citation13	ID	Discogel	Fluor	No	PL	22G	C	AP/L	ND		ND	DS	No	ND	3 h
Fukui et al^Citation14	ID	Saline sol, LA	Fluor	No	PO	22G	MPHD	AP/O/L	ND		P	ND	ND	ND	1 h
Yu et al^Citation15	ID	Cs	CT	No	ND	ND	ND	ND	ND		ND	ND	ND	ND	ND
		Saline sol
Cao et al^Citation16	ID	Cs, Songmeile	CT	No	PL	22G	C	ND	Authors		ND	ND	ND	ND	3 h
		Saline sol
Muto et al^Citation17	ID/PG/PR	Oz	CT	No	PvO	18/20G	C	ND	ND		P	ND	ND	ND	ND
Oder et al^Citation18	ID/PG/Ep	Cs, LA, Oz	CT/Fluor	No	Post	22G	C	CT scan	ND		P	Yes	Yes	Yes	12 h
Fayad et al^Citation19	ID	Cs	Fluor	No	PL	22G	C	AP/L	Radiol		ND	No	No	ND	ND
Gallucci et al^Citation20	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 al^Citation21	ID	HyD, LA	Fluor	No	ND	22G	C	ND	ND		ND	ND	ND	ND	ND
Benyahya et al^Citation22	ID	Cs	CT	No	PL	ND	C	ND	Radiol		ND	ND	ND	ND	ND
Khot et al^Citation23	ID	Cs	Fluor	No	PL	ND	ND	ND	Authors		ND	AwS	No	ND	ND
Andreula et al^Citation24	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 al^Citation25	ID	Cs	Fluor	No	PL	22G	ND	ND		ND	ND	ND	ND	ND	ND
Centeno et al^Citation43	Ep/ID	AT-MSC, LA	Fluor	No	PL	ND	ND	ND		ND	P	No	Yes	ND	ND
Zhang et al^Citation37	ID	BM	Fluor	Yes	PL	ND	C	Dis		ND	P	ND	ND	ND	24 h
Tuakli-Wosornu et al^Citation39	ID	Prp	Fluor	ND	PL	20G/25 G	C	Dis		Physiatrist	P	No	Yes	Yes	ND
Kumar et al^Citation41	ID	AT-MSC, HA	Fluor	Yes	PL	22 G	C	CT scan		Spine surgeon	P	ND	Yes	Yes	4 h
Levi et al^Citation46	ID	Prp	Fluor	ND	PL	22G/25 G	C	ND		Physiatrist	P	Yes	Yes	Yes	ND
Pettine et al^Citation35	ID	AT-BMC	Fluor	ND	PL	22G	C	ND		ND	P	No	Yes	ND	ND
Sainoh et al^Citation36	ID	TNF-α I	Fluor	ND	PL	22 G	C	RTMF		ND	LD	No	Yes	ND	ND
Noriega et al^Citation44	ND	AL-MSC	ND	ND	ND	ND	ND	ND		Radiologists	ND	ND	Yes	ND	ND
Giurazza et al^Citation38	ID	O2-O3	Fluor, CT	ND	PL, Pv/IL, TF	18–22 G	C	ND		Radiologists	P	Yes	ND	ND	ND
Pettine et al^Citation42	ID	AT-BMC	Fluor	NDd	PL	22 G	C	ND		ND	P	No	Yes	No	ND
Nguyen et al^Citation34	ID	Cs	Fluor	ND	PL	18/22 G	C	ND		Radiologists	LD	No	No	No	ND
Perri et al^Citation40	ID	O2-O3	CT	ND	Pv/IL	22 G	C	CT		Neuroradiologists	P	No	Yes	Yes	ND

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 1 Flow diagram illustrating published literature on intradiscal injection.

Figure 2 Different type of image guidance for intradiscal injection.

Kallewaard JW, Geurts JW, Kessels A, Willems P, van Santbrink H, van Kleef M. Efficacy, safety, and predictors of intradiscal methylene blue injection for discogenic low back pain: results of a multicenter prospective clinical series. Pain Pract. 2015. doi:10.1111/papr.12283

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Zhang Y, Ma Y, Jiang J, Ding T, Wang J. Treatment of the lumbar disc herniation with intradiscal and intraforaminal injection of oxygen-ozone. J Back Musculoskelet Rehabil. 2013;26(3):317–322. doi:10.3233/BMR-130386

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Lehnert T, Naguib NN, Wutzler S, et al. Analysis of disk volume before and after CT-guided intradiscal and periganglionic ozone-oxygen injection for the treatment of lumbar disk herniation. J Vasc Interv Radiol. 2012;23(11):1430–1436. doi:10.1016/j.jvir.2012.07.029

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Cao P, Jiang L, Zhuang C, et al. Intradiscal injection therapy for degenerative chronic discogenic low back pain with endplate modic changes. Spine J. 2011;11(2):100–106. doi:10.1016/j.spinee.2010.07.001

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Miller Matthew RDSc, PA-C, Mathews RSMD, PhD, Dean RKMD. Treatment of painful advanced internal lumbar disc derangement with intradiscal injection of hypertonic dextrose. Pain Physician. 2006;9:115–121.

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Benyahya R, Lefevre-Colau MM, Fayad F, et al. Intradiscal injection of acetate of prednisolone in severe low back pain: complications and patients assessment of effectiveness. Ann Readapt Med Phys. 2004;47:621–626. doi:10.1016/S0168-6054(04)00193-X

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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;15:16–31. Wiley Periodicals, Inc.

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Sainoh T, Orita S, Miyagi M, et al. Single intradiscal administration of the tumor necrosis factor-alpha inhibitor, etanercept, for patients with discogenic low back pain. Pain Med. 2016;17:40–45. doi:10.1111/pme.12892

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Kumar H, Ha DH, Lee EJ, et al. Safety and tolerability of intradiscal implantation of combined autologous adipose-derived mesenchymal stem cells and hyaluronic acid in patients with chronic discogenic low back pain: 1-year follow-up of a phase I study. Stem Cell Res Ther. 2017;8:262. doi:10.1186/s13287-017-0710-3

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Zhang XJ, Hao J, Hu ZM, Yang HT. Clinical evaluation and magnetic resonance imaging assessment of intradiscal methylene blue injection for the treatment of discogenic low back pain. Pain Physician. 2016;19:E1189–E1195.

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Perri M, Marsecano C, Varrassi M, et al. Indications and efficacy of O2–O3 intradiscal versus steroid intraforaminal injection in different types of disco vertebral pathologies: a prospective randomized double‑blind trial with 517 patients. Radiol Med. 2016;121:463–471. doi:10.1007/s11547-015-0598-x

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