The findings of the present study, consisting of 76 participants suffering from chronic lumbar and radicular lower extremity pain, revealed a statistically considerable decrease in average VAS and ODI scores following 12 months of treatment with either steroid alone or steroid plus ozone by epiduroscopic procedure. The reduction in pain severity was statistically superior in additional ozone-received cases while the improvement in disability was comparable in both groups. Epiduroscopy is performed by mechanical removal of adhesions and focused delivery of steroids alone or in combination with ozone emerges as a promising and safe modality for the prolonged management of pain in lumbar herniated discs.

The beneficial outcomes observed in both groups following epiduroscopy may be attributed to the irrigation of the epidural area with saline and the injection of steroids, which have been demonstrated to remove inflammatory agents, reduce edema, and increase the mobility of the nerve root [16]. In addition, the study showed that combining steroids with ozone led to better improvements in pain intensity. This could be attributed to the capacity of ozone and its reactive oxygen molecules’ capacity to react with proteoglycans, collagen types I and II, carbohydrates, and amino acids [8, 17].

The enhanced analgesic effect observed in the group that received additional ozone might be attributable to the volume effect of the ozone on the epidural space. Similar to saline washing the epidural space, the administration of 20 ml of ozone may have resulted in the removal of inflammatory cytokines from the epidural space.

Ozone has recently been used more widely as epidural, transforaminal, paravertebral, and intramuscular therapy. The application of ozone to the epidural area during epiduroscopy has been observed in a few studies which reported positive results [6, 18]. Masini et al. found in their retrospective study that 32 patients experienced a mean of 60% improvement in VAS scores after ozone and steroid injections into the epidural region using epiduroscopy [6]. Epidural application of ozone and steroids is an effective non-surgical procedure that can be employed in cases of refractory lumbar pain. Alexandre et al. carried out a retrospective study of patients with FBSS who underwent epiduroscopic adhesional release with the intradiscal procedure, which also yielded favorable outcomes [18].

It has been demonstrated that, upon interaction with biologically active components, ozone is capable of exhibiting a reaction involving multiple organic substances, and that results in anti-inflammatory and analgesic effects. The activation of cytokines inhibits the pro-inflammatory factors linked to persistent pain [19]. It may produce its effects by either chemical removal of scar tissue or dehydration of herniated disc contents [20]. It is thought that ozone may stimulate the activation of the descending antinociceptive pathway provided by the interruption of nociceptive signals transmitted to the thalamus and cortex [19].

Recently, the clinical efficacy of epiduroscopy in treating degenerative disc diseases has been reported in several studies [1, 5, 21, 22]. The quality of the evidence is moderate, and the recommendations are weak [1]. The pain-relieving effect may be associated with the administration of medical agents (steroids, hyaluronidase, ozone, and clonidine), in addition to mechanical dissolution, or a combination of these factors [2, 5, 6, 14, 23].

A well-planned patient selection process is considered to be a fundamental aspect of the efficacy of epiduroscopy, particularly in cases of persistent spinal pain syndrome [1]. The present study revealed that patient status, whether operated or not, did not significantly affect the results of either treatment group. The observation that the majority of patients in both treatment groups already had moderate to severe fibrous tissue may provide a rationale for these results.

In patients presenting with disc herniation or radiculopathy, a neuropathic component may be evident. Nevertheless, it is possible for a nociceptive component to be present simultaneously in the same individual. Magalhaes et al. (n = 13), reported a greater reduction in pain and disability in non-neuropathic components than in neuropathic components [24]. The improvement in pain and disability was significantly better in cases with non-neuropathic predominant pain, with improvements of 95.2%, 80.6%, and 75.3% in low back and limb pain and ODI scores, respectively. In contrast, patients with neuropathic predominant pain demonstrated only 12.5%, 42.4%, and 20.9% improvement at the six-month follow-up. In consideration of the association between nociceptive pain and chronic inflammation, the therapeutic effect of ozone on nociceptive pain might be explained by its anti-inflammatory effect. The findings of the study by Barbarosa et al. which evaluated 19 patients who had undergone epiduroscopy and received epidural ozone, demonstrated that there was a decline in pain severity; but no enhancement in functional ability [2]. They attributed these results to the uniformity of the sample, comprising exclusively individuals meeting the criteria for FBSS who exhibited moderate to high degrees of functional impairment. They suggested that epidural ozone intervention might be a suitable therapeutic strategy for FBSS. In our study, the exclusion of patients with severe stenosis may have led to a substantial decline in VAS scores as well as disability compared with the baseline values.

In their study, Manchikanti et al. observed an 80%, 56%, and 48% reduction in pain at 3,6 and 12 months, respectively, in initial pain among patients who received adhesiolysis and additional steroid and local anesthetic into the epidural space [25]. A considerable number of participants demonstrated a positive response to the treatment, with a notable alleviation of pain, enhancement in functionality, and psychological well-being. Massini et al. demonstrated sustained outcomes at the two-year follow-up following the administration of a steroid and ozone injection into the epidural space. The combination of ozone and steroids appears to provide sustained analgesia. Additionally, as suggested by Donati et al., in cases of chronic lumbar back pain with claudication, epiduroscopy with adhesion removal, the use of hyaluronidase, ciprofloxacin, and ozone has been demonstrated to be an efficacious procedure for the provision of sustained alleviation of pain, with an average success rate of 66% at 36 and 48 months, and 65% at 60 months [15]. It has also been shown to be an important factor in reducing patient disability, as demonstrated by the results of the current study. The outcomes of the treatment showed a marked decrease in both the VAS and ODI scores of the patients, with more favorable outcomes observed in the steroid and ozone-applied group, particularly in terms of the VAS scores. The variations in the outcomes of the research may be attributable to a number of variables, comprising the nature of the population, mild to severe disability levels, surgical method, type of medication, co-administration of medications, duration of postoperative evaluation, and different assessment tools used by researchers.

Compared with MRI, endoscopic evaluation of the epidural space may offer enhanced sensitivity in the detection of epidural fibrosis. In a study of one hundred and twenty-five patients, Bosscher et al. concluded that epiduroscopy was a more precise diagnostic modality than either physical examination or MRI for identifying the spinal segment involved in the pathology [26]. They suggested that epiduroscopy may be more beneficial in identifying conditions that are not primarily related to nerve root compression, therefore MRI was inferior to epiduroscopy in their study. Furthermore, the most clinically important epidural problems detected by epiduroscopy in subjects with lumbar and radicular lower extremity pain were located at the L4 to L5 segment of the spinal column, and secondarily at the L3 to L4 segment. Similarly, in the present study, L4 was identified as the most frequently affected nerve root, followed by L5.

Recently Willem et al. concluded that epiduroscopy identified the occurrence of epidural fibrosis in 91% of individuals with FBSS, whereas only 16.1% of cases were detected by MRI [21]. The distinction between soft and hard adhesions can be identified through tactile examination of the affected area. Soft adhesions are characterized by a lack of rigidity, facilitating their removal. In contrast, hard adhesions display a higher degree of rigidity, presenting a challenge to the procedure’s success. The authors suggested that the hardness of the adhesion is a crucial factor in the outcome of the procedure [21]. Better outcomes may be achieved with pain associated with mild-to-moderate fibrosis [14]. In our study, the majority of cases demonstrated moderate to severe fibrosis (94.2% and 80.5%), respectively. Even though dense fibrous tissue might lead to surgical difficulties, we considered that the careful selection of patients and the experienced clinician has a positive impact on our results. On the other hand, various research has established an absence of correlation between the severity of epidural fibrotic changes, typically measured using MRI, and symptoms [27,28,29]. The study’s findings also failed to demonstrate an association between the severity of scarring and treatment outcomes.

The extant literature on the application of ozone during epiduroscopy is limited and, this intervention is regarded as being of a minor risk classification. The therapeutic range of ozone is 10–40 ug/mL, higher than this could potentially induce vagal reflex, loss of consciousness, and gas embolism [24]. Insomnia, headache, visual disturbance, paraesthesia, pruritus, papules, gastritis, vertigo, tachycardia hot sensations, and abdominal pain are side effects associated with ozone which are more frequently reported with systemic administration [9, 30]. Intraoperative discomfort pain at the point of insertion, infection, encephalopathy, temporary neural deficits associated with fluctuations in epidural tension, lumbar or radicular pain, dural puncture, headache, and ocular deterioration linked to intraretinal bleeding are some of the potential adverse consequences of epiduroscopy [31]. In their study, Vanni et al. observed the presence of fibrotic adhesions involving the root and dural sac, as well as the presence of fragmented disc, in patients who had earlier undergone ozone administration [30]. These authors suggested that the frequency of severe consequences associated with the utilization of ozone may be underreported. No serious complications or side effects were reported in our patients. Transient paraesthesia, discomfort at the sacral access site, and post-dural puncture headaches were the short-lasting side effects after the procedure.

This study has several limitations. Firstly, it was retrospective in nature and the observation period following the intervention could have been longer (longer than one year). The lack of a control group or patients treated with ozone alone and the limited sample size were other limitations of the study. The study also has several strengths. A remarkable strength of the present study was the utilization of assessment tools such as VAS, ODI, and DN4 questionnaires. Furthermore, no significant adverse effects were observed during or following the procedure. To our knowledge, this is the only study to have compared the efficacy of epiduroscopy with steroid alone and steroid plus ozone in two groups.

In summary, the current study concluded a notable reduction in the pain and disability scores at each follow-up point throughout the 12 months in patients with lumbar and radicular limb pain related to disc herniation in both treatment groups. This improvement was particularly favorable in patients who received ozone in combination with steroids. Although there was a substantial difference in pain scores between the two groups, the difference in disability scores did not reach a significant level. Administration of steroids alone or in combination with ozone during epiduroscopy showed the ability to improve pain intensity and disability. Epiduroscopy has become a useful interventional modality in the diagnosis and treatment of pain associated with herniated intervertebral discs in the absence of serious spinal stenosis. Prospective, randomized, and blinded studies with larger sample sizes and standardized follow-up would provide more robust evidence for the prolonged impacts of epidural administration of ozone in combination with steroids and to ascertain the efficacy of the technique.