|Year : 2015 | Volume
| Issue : 2 | Page : 64-72
Efficacy of transforaminal epidural steroid injection versus intraforaminal or periforaminal ozone for low back pain with radiculopathy
Jerry Joseph Joel1, Debjyoti Dutta2, Gautam Das3, GS Anand Kumar4, Jay Panchal5, Santanu Basak6
1 Department of Anesthesia, Christian Medical College, Vellore, Tamil Nadu, India
2 Assistant Professor, College of Medicine and JNM Hospital, WBUHS, Kolkata, India
3 Consultant and Director, Daradia Pain Clinic and Institute, Kolkata, India
4 Assistant Professor, Balaji Medical College, Chennai, India
5 Consultant Pain Physician, Sanjivini Super Speciality Hospital, Ahmedabad, Gujurat, India
6 Consultant, KPC Medical College, Kolkata, India
|Date of Web Publication||15-Apr-2015|
Dr. Jerry Joseph Joel
Department of Anesthesia, Christian Medical College, Vellore - 632 002, Tamil Nadu
Source of Support: None, Conflict of Interest: None
To compare the effectiveness of transforaminal epidural steroid injection (TFESI) vs Periforaminal ozone in low back pain with radiculopathy. Literature search was done from MEDLINE and PUBMED sites. Observational studies in both steroid and ozone groups clearly favouring each other whereas there was a significant difference between the RCT's in either group. 3 RCT's out of 4 favouring ozone treatment whereas only 2 out of 8 RCT's were in favour of epidural steroids. Comparison studies showed results more in favour of combined steroid and ozone. 2 RCT's and 1 observational study were in favour of combined ozone and steroid whereas 2 RCT's favoured ozone better than steroid and ozone. Currently studies have shown epidural steroids to be effective in inflammatory origin of pain as its proven by its short duration of action whereas ozone was shown to be effective in both short and long term mainly because of its anti inflammatory action which took care of the short term pain and its ability to denature the proteins of disc material and correct the underlying pathology resulting in effective long term relief. Studies have also shown cumulative effects of ozone and epidural steroids and we would recommend a careful selection of patients for ozone or steroid to increase the success rate and further studies would be needed to know their true potential in low back pain due to radiculopathy.
Keywords: Low back pain, radiculopathy, transforaminal epidural steroid injection, periforaminal ozone
|How to cite this article:|
Joel JJ, Dutta D, Das G, Anand Kumar G S, Panchal J, Basak S. Efficacy of transforaminal epidural steroid injection versus intraforaminal or periforaminal ozone for low back pain with radiculopathy. Indian J Pain 2015;29:64-72
|How to cite this URL:|
Joel JJ, Dutta D, Das G, Anand Kumar G S, Panchal J, Basak S. Efficacy of transforaminal epidural steroid injection versus intraforaminal or periforaminal ozone for low back pain with radiculopathy. Indian J Pain [serial online] 2015 [cited 2019 Mar 23];29:64-72. Available from: http://www.indianjpain.org/text.asp?2015/29/2/64/155172
| Introduction|| |
The lumbosacral region is a critical area in the spinal column subjected to forces greater than elsewhere in the body with an acute change in the direction of transmission of forces at this level. Low back pain (LBP) is one of the most common complaints that a patient presents with at a pain clinic. It has been an important clinical, social, economic, and public health problem affecting the human population worldwide.  Around 70% of adults suffer from LBP at some point in their lifetime with various degrees of symptom severity. In addition, 1.6-43% of these patients have LBP associated with sciatic symptoms.  Back pain is often caused by disc-disease even though other factors are responsible for nerve root syndromes and should be entertained when clinical symptoms fail to correlate with computed tomography (CT) and/or magnetic resonance (MR) findings. 
Nevertheless, the natural history of lumbar disk herniation is favorable. Improvement of symptoms is the norm, and most episodes resolve spontaneously or after conservative therapy. , The natural history of lumbar disk herniation has been elucidated by means of serial imaging studies, which showed spontaneous clinical and anatomic resolution in 67-76% of patients after 1-year. ,,,, Therefore, an invasive approach is reserved for patients failing to respond to conservative treatment.
Until 15 years ago, surgery was the treatment of choice, but conservative measures are now preferred in the wake of unsatisfactory surgical outcomes.  Pain resolution is present in no more than 80-85% of patients,  and a failed back surgery syndrome develops in 10-40% of patients.  In the past decades, many new minimally invasive image-guided interventional techniques have been developed to reduce the need for surgery and to improve the quality-of-life of patients requiring systemic drugs. ,, Yet, few of these treatments have been tested in controlled randomized studies.
Percutaneous techniques minimize the invasive nature of surgery, rendering administration more straightforward and faster while sparing healthy tissue and avoiding or minimizing complications like postsurgical infection.  Among the techniques adopted in the past decade to treat sciatic nerve pain caused by a herniated disk or nondiscal spinal disease are the periradicular infiltration of a steroid and the intraforaminal injection of an oxygen-ozone (O 2 -O 3 ) gas mixture. Both methods have yielded encouraging results. ,,,
In 1930, Evans reported that sciatica could be treated by epidural injection. The use of epidural corticosteroid injections for the treatment of axial and radicular back pain was first reported in 1953.  Epidural steroid injections are currently used by many medical professionals for the treatment of lumbosacral radiculopathy. Performing "blind" epidural steroid injection lacks target-specificity that often results in incorrect delivery of medication to the lesion. Imaging-guided steroid injections are now becoming more popular despite the controversy regarding their efficacy.
Nevertheless, the benefit and most effective route of administration for epidural steroids remain controversial.  Interlaminar and caudal epidural injections require relatively large volumes of injectate to deliver the steroid to the presumed pathologic site, and these types of injections also have the risk of extra-epidural and intravascular needle placement. The transforaminal approach is target-specific and requires the smallest volume to reach the primary site of pathology; specifically, the anterior-lateral epidural space as well as the dorsal root ganglion. Thus, transforaminal epidural steroid injection (TFESI) under fluoroscopic guidance has emerged as the preferred approach to the epidural space. ,, Some reports have demonstrated the efficacy of TFESI for the treatment of radiculopathy.
Recently, ozone therapy has emerged as an alternative or additional treatment option for these patients, particularly in Europe. , Despite its widespread use to treat a variety of conditions, ozone therapy remains unknown to most physicians. The use of medical ozone in the treatment of LBP was first developed by an orthopedic surgeon Verga in 1980's. He has treated nearly 8000 patients over a period of 15 years with a relapse of <2% of cases. The injection is mainly made into the paravertebral muscles and in the hernia zone. 
Ozone (O 3 ) is an allotropic form of oxygen, primarily known for its ecological properties, industrial application and therapeutic effects. Questions persist concerning its potential toxicity as an oxidant agent versus its reported clinical efficacy. Several mechanisms of action have been proposed to explain the efficacy of ozone therapy including analgesic, anti-inflammatory and oxidant action on proteoglycans (e.g., in the nucleus pulposus). Ozone is administered in the form of an O 2 -O 3 gas mixture at nontoxic concentrations ranging from 1 to 40 μg of ozone/ml of oxygen, using various percutaneous methods.  However, the effectiveness of ozone injections for the treatment of LBP remains a matter of debate.
In this review, we have done a literature search on the studies available on in favor of transforaminal epidural steroid and periradicular ozone injections and tried to find out the efficacy of them in patients on LBP with lumbar radiculopathy.
| Evidences in on Transforaminal Epidural Steroid|| |
A review of available literature was done on studies analyzing the efficacy of transforaminal or periganglionic/periradicular epidural steroids. Studies by Zennaro et al., Lutz et al., Jamadar et al. and Vad et al. found promising results whereas randomized controlled trial's (RCT's) by Karppinen et al., Manchikanti et al., Cuckler et al. and Huighes et al. failed to demonstrate the superiority of epidural steroids.
Zennaro et al.  evaluated the efficacy of direct intraforaminal steroid injections into the periganglionic space in the treatment of radicular pain. Periganglionic infiltrations were performed in 41 patients with acute or chronic radicular pain. 29 patients (71%) had relief of pain and 12 (29%) had either no relief or minimal pain reduction. In patients with degenerative foraminal stenosis, 95% of patients had significant pain relief, whereas in patients with foraminal herniated disks, only 45% of the patients had pain relief. They suggested that in the former case, interruption of the self-maintained pain cycle caused by blocking the repeated nociceptive influx might explain the good results they obtained, whereas in the latter group, continuous stimulation was more difficult to control. They concluded that intraforaminal infiltration produced satisfactory pain relief in 70% of patients.
Lutz et al. in 1998  did an outcome study on fluoroscopic TFESI in patients with chronic leg pain to determine the therapeutic value and long-term effects in 69 patients. Successful long-term outcome was 75.4% with more than 50% pain relief between pre and postinjection scores and patients returned to their near previous levels of function with only after 1.8 injections per patient (avg.: 1-4 injections). They concluded that Fluoroscopic TFESI is an effective nonsurgical treatment for patients with lumbar disk herniation and radiculopathy and should be considered before surgery.
Similar results were found by Jamadar et al.  in India. They did a prospective observational study on the efficacy of epidural steroid in chronic LBP inn 56 patients. They found the success rate of epidural steroid 83.92% with only 10.71% failure (6 patients out of 56 got no pain relief). They too concluded epidural steroid as an effective treatment in patients with chronic LBP for those patients who failed to respond to conservative treatment and should be the choice before surgery.
There have been multiple double-blind RCT's done to determine the efficacy of epidural steroids in lumbar radicular pain. Vad et al.  conducted a prospective RCT to assess the efficacy of TFESI in patients with lumbar radiculopathy secondary to prolapsed intervertebral disc (PIVD). Of the 50 consecutively assigned patients, 25 received lumbar TFESI (LTFESI), and 25 received paravertebral trigger point injections (TPIs). Successful outcomes required a patient satisfaction score of good or very good, a five point or better improvement on the Roland Morris score and pain reduction >50% at least 1-year following treatment. After an average follow-up period of 16 months, the group receiving LTFESI had a success rate of 84% as compared to 48% of the group receiving TPIs. They concluded that fluoroscopically guided transforaminal injections serve as an important tool in the nonsurgical management of lumbosacral radiculopathy secondary to a herniated nucleus pulposus. In critique, neither the reviewers nor patients were masked to treatment; thus, the quality of the placebo control was compromised (i.e., TPIs were performed at the office visit). This study provides Level II therapeutic evidence that for patients with PIVD, LTFESI is more often effective (84%) than TPIs (48%) in providing at least 50% relief of radicular pain at 16 months.
Karppinen et al.  did a study on periradicular infiltration for sciatica in Finland, among 160 patients. A similar trial has been recently done at Kentucky, USA by Manchikanti et al. in 2014  on TFESI in chronic lumbar disc herniation including 120 patients. Cuckler et al.  conducted an RCT on epidural steroids in the treatment of lumbar radicular pain in 73 patients. Huighes et al. in 2014  did a single-blind RCT on "steroid injections added to usual treatment of lumbar radicular syndrome" in 63 patients at Netherlands.
Karppinen et al. randomized them into two groups, steroid and saline group of 80 patients each. Steroid group received 40 mg methylprednisolone and 0.5% bupivacaine whereas saline group received 0.9% normal saline. Total volume was 2-3 ml in both the groups. Manchikanti et al. randomized them into two groups of 60 patients each, administering 1.5 ml of 1% lidocaine plus 0.5 ml of normal saline to Group 1 and 1.5 ml of 1% lidocaine plus 0.5 ml (3 mg) of betamethasone in Group 2 making up to total volume of 2 ml in both groups. Cuckler et al. randomized 73 patients into two groups, administering 2 ml methylprednisolone (40 mg/ml) plus 5 ml 1% procaine in Group 1 and 2 ml saline plus 5 ml 1% procaine in Group 2, constituting a total volume of 7 ml in both groups. Spijker-Huiges et al. randomized patients into two groups, care as usual and segmental epidural steroid injection group (SESI). SESI group received 80 mg triamcinolone in 10 ml normal saline.
Karppinen et al. showed that immediate leg pain relief was statistically significant in steroid group (61%) compared to saline group (44%) (P = 0.02) whereas immediate back pain relief was not statistically significant (P = 0.36). At 2 weeks, leg pain relief and patient satisfaction were significant in steroid group (P < 0.01, 0.03), whereas at 4 weeks, 3 and 6 months no significant difference was seen (P > 0.17, > 0.15). They concluded that steroid provided only short-term leg pain relief with an associated rebound pain at 3-6 months. Manchikanti et al. found that at 3 weeks there was significant pain relief in 80% of local anesthetic group and 73% in steroid group and at 2 years significant improvement was seen in 65% of local anesthetic and 57% in steroid group. They concluded that transforaminal epidural injections of local anesthetic with or without steroids might be an effective therapy for patients with disc herniation or radiculitis. The present evidence illustrates the lack of superiority of steroids compared with local anesthetic at 2-year follow-up. Similar results were found by Cuckler et al. who found no statistical significant difference between both the groups and long-term follow-up failed to demonstrate the efficacy of second epidural steroid injection. Even Spijker-Huiges et al. in their study found that SESI patients were more satisfied and less painful (P = 0.006), with significant numerical rating scale (NRS) back pain (P = 0.0115) and NRS self-perceived impairment (P = 0.0361). They concluded that the difference was too small to be considered clinically relevant and that they do not recommend SESI for patients with lumbar radicular syndrome as regular treatment.
| Evidences on Periradicular Ozone Therapy|| |
In order to investigate the effectiveness of ozone therapy for this specific purpose, we performed a review of available literature, focusing on observational studies and RCTs in patients with subacute or chronic LBP.
Two prospective observational studies have been done by Muto et al. in 2004 and 2008 in Italy. They included 2200 patients in 2004 study  "treatment of herniated lumbar disc with intradiscal and intraforaminal injection of O 2 -O 3 ." Ozone was injected intradiscally 3-4 ml and 10 ml intraforaminally at concentration of 30 μg/ml. Patients were followed up at 6 and 18 months after treatment. Outcome was assessed using modified McNab method as excellent, good and poor. At 6-month follow-up, they found 80% success (excellent 40%, good 40%) in degenerative disk-disease with herniation and 77% success (excellent 64%, good 13%) in L4-L5/L5-S1 herniated disc and 69% in multiple disc herniations whereas failure rates were high 50% in herniated disc with stenosis. At 18 months follow-up, similar results were observed. They concluded that ozone treatment has given a safer, cheaper, reliable, and easier alternative to previously existing modality of treatment. They attributed the failure in their patients mostly with spinal canal stenosis, recurrent herniated disk, calcified herniated disk, and small descending herniated disk of the lateral recess with significant nerve compression. They also recommended careful selection of patients to avoid broadening the indication for treatment of patients, thereby ensuring high success rate.
Similar study with similar results were found again by Muto et al. in 2008  on a larger study group involving 2900 patients. They did intradiscal and periforaminal ozone injections in patients with LBP and sciatica. 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. They conclude that minimally invasive percutaneous treatment by intradiscal, periradicular, or periganglionic O 2 -O 3 infiltration is a valuable and competitive technique that provides excellent results at low cost and without complications.
Findings of a randomized controlled study to assess the effectiveness of intraforaminal injection of O 2 -O 3 versus steroids have been recently published, with O 2 -O 3 injection being more effective than steroids.  Combined intradiscal and periganglionic injection of medical ozone and periganglionic injection of steroids has been found to have a cumulative effect that enhances the overall outcome of treatment for pain caused by disk herniation.  The cumulative effect of ozone and steroid was found to be superior to the effect of administering ozone or steroid alone by found by Andruela et al.  and Gallucci et al.  Similar results were also found by Masini and Calaca. 
| Comparative Studies Between Ozone and Steroid|| |
In order to study the efficacy of ozone and steroid, we reviewed the available articles. Andruela et al. in 2003  did a randomized control trial in Italy on 600 patients with lumbar disc herniation treated with a single session of ozone therapy. All presented with clinical signs of lumbar disk nerve root compression, with CT and/or MR evidence of contained disk herniation. They randomized patients into two groups of 300 each, where Group A received 4 ml intradiscal and 8 ml periganglionic ozone at 27 μg/ml concentration. Group B received ozone in similar concentration plus steroid (1 ml depomedrol 40 mg/ml) and 0.5% marcaine. Outcome was assessed using modified macnab method. Treatment was success in 211 (70.3%) patients in Group A with excellent in 151 and good in 60 patients and 235 (78.3%) in Group B patients with excellent 160 and good in 75 patients (P < 0.05). They concluded that O 2 -O 3 therapy is a useful treatment for lumbar disk herniation that has failed to respond to conservative management and has a significant cumulative effect.
Masini and Calaca in 2011  studied the epidural endoscopy targeted delivery of ozone and steroid in 32 consecutive patients with refractory LBP. Follow-up revisions with 1, 3, 6, 12, and 24 months showed persistent improvement percentage at mean 60%. The Oswestry Disability Index showed significant changing in status pre and postprocedure related to the pain control condition. No serious complications were related to the procedure. They concluded that the association with ozone (O 2 /O 3 ) and steroids seems to result in a long lasting pain relief, giving to the physician and to the patient a wider window to work on the treatment of other frequently associated causes (emotional, socioeconomic, and environmental) of refractory back pain. They showed similar cumulative effects as observed by Andruela et al.
Gallucci et al. in 2007  conducted an RCT in Italy on 159 patients with lumbar radiculopathy. Group A (77 patients) received steroid, 2 ml triamcinolone (40 mg/ml) -1 ml intradiscal and 1 ml intraforaminal and 2-4 ml of 2% ropivacaine. Group B (82 patients) received same dose of steroid and local anesthetic with ozone 5-7 ml intraforaminal and 5-7 ml intradiscal at 28 μg/ml. They found no significant difference between the outcomes of both groups at 2 weeks and 3 months (P = 0.72, P = 0.136 respectively). At 6 months follow-up, success rate was statistically significant in Group B (74%) compared to Group A (47%) (P < 0.01). They suggested that ozone was the only difference between the two treatments and, therefore, the better outcome in Group B should be due to the pharmacologic actions of ozone. Similar results have also been reported by D'Erme et al.,  Muto et al.  and Paradiso and Alexandre. 
A study done by Zhang et al. in 2013  showed no significant difference between ozone and ozone steroid mixture and had suggested ozone therapy as first choice before recourse to surgery without the need for addition of steroid. They had randomized 172 patients with lumbar disc herniation into two groups. Group A (90 patients) received intradiscal and intraforaminal ozone, and Group B (82 patients) received ozone plus steroid (1 ml betamethasone) and were followed-up at 3 weeks, 6 months, and 12 months. Outcome was assessed using visual analog scale (VAS) and Japanese orthopedic association (JOA) evaluation system. Reduction of VAS from baseline to end of the study was 7.68-2.17 in Group A and 7.49-2.23 in Group B. At 3 weeks, JOA recovery rates were better in Group B than Group A. No significant difference was found at 3 and 6 months follow-ups.
Bonetti et al. in 2005  did a double-blinded RCT in Italy comparing Intraforaminal ozone versus periradicular steroid infiltration in 306 patients with acute or chronic LBP with sciatic nerve pain. On the basis of depicted neuroradiological changes magnetic resonance imaging, patients were divided into two groups: The disk-disease (bulging disk, protrusion or herniation) with 166 patients and nondisk-disease group (osteophytosis, spondylolysis, facet joint syndromes) with 140 patients. Half of each group patients received 2 ml of periradicular steroid (methylprednisolone 40 mg/ml), and the other half received ozone 3 ml close to the neural foramen at 25 μg/ml concentration. Outcomes were assessed using modified mcNAB method. At short-term follow-up (1-week), patients in both the groups had complete remission of pain (84.8% vs. 80%) but the difference was not statistically significant between the groups (P = 0.407). At medium-term follow-up (3 months), again the difference was not statistically significant (P = 0.13, P = 0.24 for disk and nondisk-disease group, respectively). At long-term (6 months) follow-up, significant difference was found in favor of ozone in disk-disease group 64 (74.4%) out of 86 patients compared to 46 (57.5%) out of 80 patients in the steroid group (P = 0.0021) but not in nondisk-disease group (P = 0.0992). They concluded that no biochemical evidence suggesting short or long-term adverse effects linked to ozone and ozone treatment has proved highly effective in relieving acute and chronic LBP with sciatica. They have suggested administration of ozone gas as a first choice treatment to replace epidural steroid to avoid surgery [Table 1] and [Table 2].
| Discussion|| |
We can see that from the above table, both the epidural steroids and ozone treatment have similar number of studies in favor of each other. Observational studies in both steroid and ozone groups clearly favoring each other whereas there was a significant difference between the RCT's in either group. 3 RCT's out of 4 favoring ozone treatment whereas only 2 out of 8 RCT's were in favor of epidural steroids. Comparison studies showed results more in favor of combined steroid and ozone. 2 RCT's and 1 observational study were in favor of combined ozone and steroid whereas 2 RCT's favored ozone better than steroid and ozone.
The rationale for anti-inflammatory treatment with periganglionic steroid infiltration is the relief of the periganglionic inflammation by ensuring recovery of the normal ganglioneural myelin sheath, and hence nerve function, at the disease site , and is an effective tool for the relief of root pain caused by spondylosis or disk herniation, but the effects appear to be short lived. , This was particularly true in patients in the disk-disease group, in whom the rate of excellent outcomes fell from 80% in the short-term to 57.6% at long-term follow-up. Furthermore, undesired severe reactions, such as arachnoiditis, meningitis, paraparesis, paraplegia, sensory disorders, bowel/bladder dysfunction, headache, and epilepsy after steroid administration should also be considered. ,,,
From the above studies, it is clear that epidural steroid has a definite role in short-term pain relief in patients with chronic LBP with radiculopathy but several RCT'S have failed to show its lack of long-term effects and lack of superiority of steroids with placebo even in short-term relief. Furthermore, there has been documentation of rebound pain after epidural steroids after 3-6 months and many authors have failed to recommend epidural steroid as regular treatment for lumbar radicular pain owing to its clinical efficacy and relevance showing wide variability in multiple studies and the possible life-threatening complications associated with epidural steroid. All these led to rise of an alternative treatment which is safe, effective, and with good long-term effects.
The O 2 -O 3 gas mixture injected proximal to the root ganglion is thought to normalize the levels of cytokines and prostaglandins, increase superoxide dismutase levels, minimize reactive oxidant species, and improve local periganglionic circulation with a eutrophic effect on the nerve root. ,, This effect was especially evident at short-term follow-up in patients without disk-disease, roughly 80% of who reported a clear improvement in symptoms; this observation demonstrating that both treatments rapidly relieve nondiscal pain. The medium and long-term results marginally favored O 2 -O 3 treatment, especially in patients with painful disk-disease. A statistically significant trend, with a relatively smooth slope, was noted in patients with disk-disease group treated with O 2 -O 3 infiltration, in whom the rate of excellent outcomes decreased from 84.8% at short-term follow-up to 74.4% at long-term follow-up (P = 0.0021). Interesting finding in this study was the increase in the number of patient with disk-disease (disk-induced pain) who reported an improvement in symptoms with ozone. This finding supports other evidence that O 2 -O 3 infiltration affects not only the symptoms but also the cause of pain by accelerating the natural recovery mechanism of disk herniation. 
| Conclusion|| |
From the overall review of articles, TFESI have been found to have a short duration of action and many studies have failed to demonstrate its efficacy in long-term and against local anesthetic and saline placebo. On the other hand, ozone has been found to be very safe, cheap, and effective even in long-term for patients with back pain along with sciatic nerve pain. No biochemical side effects have been reported so far whereas epidural steroids have their potential life-threatening side effects and need to be cautiously used. Currently, studies have shown epidural steroids to be effective in inflammatory origin of pain as its proven by its short duration of action whereas ozone was shown to be effective in both short and long-term mainly because of its anti-inflammatory action which took care of the short-term pain and its ability to denature the proteins of disc material and correct the underlying pathology resulting in effective long-term relief. Studies have also shown cumulative effects of ozone and epidural steroids and we would recommend a careful selection of patients for ozone or steroid to increase the success rate and further studies would be needed to know their true potential in LBP due to radiculopathy.
| References|| |
Freynhagen R, Baron R, Gockel U, Tölle TR. painDETECT: A new screening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin 2006;22:1911-20.
Kaki AM, El-Yaski AZ, Youseif E. Identifying neuropathic pain among patients with chronic low-back pain: Use of the Leeds Assessment of Neuropathic Symptoms and Signs pain scale. Reg Anesth Pain Med 2005;30:422-8.
Muto M, De Maria G, Izzo R, Fucci G, Aprile I. Nondiscal lumbar radiculopathy: Combined diagnostic approach by CT and MR. Riv Neuroradiol 1997;10:165-73.
Saal JA. Natural history and nonoperative treatment of lumbar disc herniation. Spine (Phila Pa 1976) 1996;21:2S-9.
Komori H, Shinomiya K, Nakai O, Yamaura I, Takeda S, Furuya K. The natural history of herniated nucleus pulposus with radiculopathy. Spine (Phila Pa 1976) 1996;21:225-9.
Bozzao A, Gallucci M, Masciocchi C, Aprile I, Barile A, Passariello R. Lumbar disk herniation: MR imaging assessment of natural history in patients treated without surgery. Radiology 1992;185:135-41.
Bush K, Cowan N, Katz DE, Gishen P. The natural history of sciatica associated with disc pathology. A prospective study with clinical and independent radiologic follow-up. Spine (Phila Pa 1976) 1992;17:1205-12.
Delauche-Cavallier MC, Budet C, Laredo JD, Debie B, Wybier M, Dorfmann H, et al.
Lumbar disc herniation. Computed tomography scan changes after conservative treatment of nerve root compression. Spine (Phila Pa 1976) 1992;17:927-33.
Gallucci M, Bozzao A, Orlandi B, Manetta R, Brughitta G, Lupattelli L. Does postcontrast MR enhancement in lumbar disk herniation have prognostic value? J Comput Assist Tomogr 1995;19:34-8.
Splendiani A, Puglielli E, De Amicis R, Barile A, Masciocchi C, Gallucci M. Spontaneous resolution of lumbar disk herniation: Predictive signs for prognostic evaluation. Neuroradiology 2004;46:916-22.
Davis RA. A long-term outcome analysis of 984 surgically treated herniated lumbar discs. J Neurosurg 1994;80:415-21.
Osborn AG. Nonneoplastic disorders of the spine and spinal cord. In: Diagnostic Neuroradiology. St. Louis, Mo: Mosby; 1994. p. 820-75.
Choy DS, Ascher PW, Ranu HS, Saddekni S, Alkaitis D, Liebler W, et al.
Percutaneous laser disc decompression. A new therapeutic modality. Spine (Phila Pa 1976) 1992;17:949-56.
Onik G, Helms CA, Ginsburg L, Hoaglund FT, Morris J. Percutaneous lumbar diskectomy using a new aspiration probe. AJR Am J Roentgenol 1985;144:1137-40.
Wittenberg RH, Oppel S, Rubenthaler FA, Steffen R. Five-year results from chemonucleolysis with chymopapain or collagenase: A prospective randomized study. Spine (Phila Pa 1976) 2001;26:1835-41.
Manchikanti L, Boswell MV, Singh V, Benyamin RM, Fellows B, Abdi S, et al.
Comprehensive evidence-based guidelines for interventional techniques in the management of chronic spinal pain. Pain Physician 2009;12:699-802.
Iliakis E. Ozone treatment in low back pain. Orthopaedics 1995;1:29-33.
Andreula CF, Simonetti L, De Santis F, Agati R, Ricci R, Leonardi M. Minimally invasive oxygen-ozone therapy for lumbar disk herniation. AJNR Am J Neuroradiol 2003; 24:996-1000.
Andreula CF. Lumbosacral disc herniation and correlated degenerative disease: Spinal interventional chemodiscolysis with O3. Riv Neuroradiol 2001;14:81-8.
Fabris G, Tomassini G, Lavaroni A. Percutaneous treatment of lumbar herniated disk. Riv Neuroradiol 1997;10:13-22.
Sitzman BT. Epidural injection. In: Fenton DS, Czervionke LF, editors. Image-guided Spine Intervention. Philadelphia: Saunders; 2003. p. 99-126.
Chou R, Atlas SJ, Stanos SP, Rosenquist RW. Nonsurgical interventional therapies for low back pain: A review of the evidence for an American Pain Society clinical practice guideline. Spine (Phila Pa 1976) 2009;34:1078-93.
Vad VB, Bhat AL, Lutz GE, Cammisa F. Transforaminal epidural steroid injections in lumbosacral radiculopathy: A prospective randomized study. Spine (Phila Pa 1976) 2002;27:11-6.
Gajraj NM. Selective nerve root blocks for low back pain and radiculopathy. Reg Anesth Pain Med 2004;29:243-56.
Postacchini F, Postacchini R. Operative management of lumbar disc herniation: The evolution of knowledge and surgical techniques in the last century. Acta Neurochir Suppl 2011;108:17-21.
Bocci VA. Scientific and medical aspects of ozone therapy. State of the art. Arch Med Res 2006;37:425-35.
Muto M, Avella F. Percutaneous treatment of herniated lumbar disc by intradiscal oxygen-ozone injection. Interv Neuroradiol 1998;4:279-86.
Zennaro H, Dousset V, Viaud B, Allard M, Dehais J, Sénégas J, et al.
Periganglionic foraminal steroid injections performed under CT control. AJNR Am J Neuroradiol 1998;19:349-52.
Lutz GE, Vad VB, Wisneski RJ. Fluoroscopic transforaminal lumbar epidural steroids: An outcome study. Arch Phys Med Rehabil 1998;79:1362-6.
Jamadar NP, Ganesh K, Sandeep G, Joshi V, Vikram S. Efficacy of epidural steroid injections in management of chronic low back pain. Indian J Basic Appl Med Res 2013;2:903-11.
Karppinen J, Ohinmaa A, Malmivaara A, Kurunlahti M, Kyllönen E, Pienimäki T, et al.
Cost effectiveness of periradicular infiltration for sciatica: Subgroup analysis of a randomized controlled trial. Spine (Phila Pa 1976) 2001; 26:2587-95.
Manchikanti L, Cash KA, Pampati V, Falco FJ. Transforaminal epidural injections in chronic lumbar disc herniation: A randomized, double-blind, active-control trial. Pain Physician 2014;17:E489-501.
Cuckler JM, Bernini PA, Wiesel SW, Booth RE Jr, Rothman RH, Pickens GT. The use of epidural steroids in the treatment of lumbar radicular pain. A prospective, randomized, double-blind study. J Bone Joint Surg Am 1985;67:63-6.
Spijker-Huiges A, Winters JC, van Wijhe M, Groenier K. Steroid injections added to the usual treatment of lumbar radicular syndrome: A pragmatic randomized controlled trial in general practice. BMC Musculoskelet Disord 2014;15:341.
Muto M, Andreula C, Leonardi M. Treatment of herniated lumbar disc by intradiscal and intraforaminal oxygen-ozone (O2-O3) injection. J Neuroradiol 2004;31:183-9.
Muto M, Ambrosanio G, Guarnieri G, Capobianco E, Piccolo G, Annunziata G, et al.
Low back pain and sciatica: Treatment with intradiscal-intraforaminal O (2)-O (3) injection. Our experience. Radiol Med 2008;113:695-706.
Bonetti M, Fontana A, Cotticelli B, Volta GD, Guindani M, Leonardi M. Intraforaminal O(2)-O(3) versus periradicular steroidal infiltrations in lower back pain: Randomized controlled study. AJNR Am J Neuroradiol 2005;26:996-1000.
Gallucci M, Limbucci N, Zugaro L, Barile A, Stavroulis E, Ricci A, et al.
Sciatica: Treatment with intradiscal and intraforaminal injections of steroid and oxygen-ozone versus steroid only. Radiology 2007;242:907-13.
Masini M, Calaça A. Minimally invasive treatment for refractory low back pain, targeted by epidural endoscopy with O2/O3 and steroid therapy. Acta Neurochir Suppl 2011;108:33-7.
D'Erme M, Scarchilli A, Artale AM, Pasquali Lasagni M. Ozone therapy in lumbar sciatic pain. Radiol Med 1998;95:21-4.
Paradiso R, Alexandre A. The different outcomes of patients with disc herniation treated either by microdiscectomy, or by intradiscal ozone injection. Acta Neurochir Suppl 2005;92:139-42.
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;26:317-22.
[Table 1], [Table 2]