Retrospective observational study of intramuscular oxygen-ozone therapy for the treatment of neck pain: cervical paravertebral injection.

Neck pain is one of the major pathologies responsible for loss of labor. Many conservative treatment methods for neck pain have been described. The purpose of this study was to obtain pain scores for patients undergoing paravertebral ozone-oxygen (O3/O2) injections for neck pain caused by cervical disc disease. Over the last 6 months of 2018, 72 patients who undergoing intramuscular O3/O2 injections to treat neck pain were examined retrospectively in this multicenter study. Patients were injected with 30 mL of 20 μg/mL O3/O2 gas (into the paravertebral space). Subjects were treated once a week for 6 weeks. The visual analog scale pain scores and Japanese Orthopedic Association scores were obtained before (pre-injection) and after treatment (i.e., at 2 and 6 months). Significant improvements were observed in visual analog scale and Japanese Orthopedic Association scores at both 2 and 6 months versus the pre-injection scores. There was no significant difference in the visual analog scale or Japanese Orthopedic Association scores between 2 and 6 months. Paravertebral O3/O2 injection is a reliable and effective treatment of neck pain caused by cervical disc disease. The study was approved by Umraniye Education and Research Hospital, University of Health Sciences, Turkey (Reference Number: 00102187854) on September 25, 2019.

INTRODUCTION

Neck pain secondary to disc degeneration or hernia is a significant health problem resulting in disability. After back pain, neck pain is the musculoskeletal condition most responsible for primary care consultations worldwide.1 The majority of adults experience at least one significant episode of axial neck pain during their lives.23 Based on studies using the same definition of neck pain, the prevalence ranges from 16.7% to 75.1% (mean, 37.2%) within the entire adult population (aged 17–70 years).14 Muscle strains and ligament sprains are common causes of acute axial neck pain. Spondylotic or degenerative causes include disc degeneration, facet arthrosis and, less commonly, segmental instability. Degenerative discs may lead to generalized axial neck pain. Consensus exists regarding surgical indications for several common cervical spine disorders, such as myelopathy, radiculopathy, and traumatic conditions characterized by instability or neurologic deficit.56 Recently many treatment methods have been tried to decrease the pain, particularly because of cervical disc disease.78 Especially, insufficiency of some drugs (paracetamol, non-steroidal anti-inflammatory, and myorelaxant) to effectively treat neck pain has prompted a search for alternative treatments.910

Paravertebral injection with O3/O2 (ozone-oxygen mixture) is a technique that can be applied easily. Ozone gas is derived from a variety of sources and shows numerous beneficial effects, including inhibition of inflammation, correction of ischemia and venous stasis, and antinociceptive activity in reflex therapy.1112 Paravertebral injection with O3/O2 has mostly been used in the treatment of lower back pain13141516; few studies have applied this technique to cervical pain.171819

Ozone therapy for disc diseases is generally applied using the intradiscal method. In this study, we show that paravertebral ozone injection administered via an “intradiscal external method” can provide the same effects. However, the optimal dose of ozone remains unclear. The aim of our multicenter study was to demonstrate the efficacy and reliability of ozone gas administered by injection for treating neck pain.

SUBJECTS AND METHODS

Design

This study was allowed by Umraniye Education and Research Hospital, University of Health Sciences, Turkey (Reference No. 00102187854) on September 25, 2019. Patients undergoing intramusculer oxygen-ozone injections for neck pain were examined retrospectively over the last 6 months of 2018 in Umraniye Education and Research Hospital, Basari Hospital, Sancaktepe Ilhan Varank Education and Research Hospital. Only patients aged between 18 and 70 years were included. Patients with cervical discogenic pain20 were enrolled regardless of whether disc degenerative disc was found on magnetic resonance imaging (MRI) in the past year. Other patients for enrollment included patients with spinal stenosis, who are not considered as surgical candidates, patients with radial root compression, and patients with pain for over 6 weeks and a visual analog scale (VAS)21 score above 5. The patients did not receive physical therapy during ozone therapy, and patients who underwent physical therapy up to 3 months before starting ozone therapy were excluded from the study. Patients were free to use non-steroidal anti-inflammatory drugs during treatment.

A total of 72 patients analyzed retrospectively in this study. Study was conducted in accordance with principles for human experimentation as defined in the Declaration of Helsinki. An informed consent was obtained from all the patients prior to the injection.

Treatment procedure

Patients received paravertebral oxygen-ozone injections (30 mL of 20 μg/mL O3/O2 gas) in the paravertebral space once a week for 6 weeks. Injection performed all patients with gas produced by ozone generator system (TURKOZONE Blue S; Ozon Sağlık, İstanbul, Turkey). Subjects with cervical discogenic pain received injection in the left and right side up to C3–T1.

The patient is placed in the prone position with the neck flexed at 30°, and the C7 cervical spinous process is palpated. Spinous protrusions of the vertebrae above and below the disc with cervical discopathy can be located using the C7 spinous protrusion as a guide. The area is cleaned with alcohol and a 13-mm needle tip is injected vertically 2 cm above and below the disc, starting 1 cm lateral to the spinous protrusion in the region of the disc. An average of 15 mL of O3/O2 is injected into the right and left side of the disc.

Outcomes

The VAS scores and Japanese Orthopedic Association (JOA) scores22 were measured before paravertebral ozone injection, and at 2 and 6 months after the last injection. The scores of the patients were performed by an orthopedist who did not know the radiological images of the patients and did not apply the ozone injection.

Statistical analysis

The statistical analysis was performed using IBM SPSS Statistics 22 software (IBM Corp., Armonk, NY, USA). Pre- and post-injection values were compared using the Mann Whitney U test. A P value of < 0.05 was considered significant.

RESULTS

O3/O2 injections were applied in 72 patients with neck pain (32 males and 40 females). The mean age was 55 years (range: 30–70 years). At 6 months after the O3/O2 injections, the final assessments were performed. On MRI, 30 subjects had bulging disc herniations, and 22 had degenerative discs and facet arthrosis. Furthermore, 10 had radicular pain and 10 had mechanical neck pain. The mean duration of pain before injection was 6.2 months (3–18 months).

We found a significant improvement in the VAS and JOA scores at 2 and 6 months after O3/O2 injection relative to the pre-injection scores (P < 0.001). No significant difference in the VAS or JOA scores between 2 and 6 months after O3/O2 injection (P > 0.05) (). No complications of neck pain patients with O3/O2 injection were observed.

DISCUSSION

In addition to drugs, physical therapy, and steroid injections, physicians have used conservative and non-invasive methods to manage cervical symptoms. According to recent studies, the pain-reducing effects of ozone may be similar, if not identical, to those of steroid injection.1523 Similar to steroids, the anti-inflammatory effect of ozone had been exploited in joint and paravertebral muscle injections.24 Ozone is typically mixed with oxygen when administered for common spine conditions. Ozone is a three-molecule atom with less stability than oxygen. Thus, it evokes a larger biological response. Ozone blocks an inflammatory enzyme known as phospholipase A2, which is also blocked by pain-relieving steroid injections.23 The limited (if any) side effects of ozone represent an important advantage over steroid injections.

Complications of ozone injection have not been widely described in the literature.23 However, gas embolism related to paravertebral ozone injection has been reported in the last few years as a major complication. Freund et al.25 reported a 34-year-old man with chronic neck pain who was treated with regular cervical paravertebral ozone injections. After the last injection, multifocal stroke occurred. Angiography revealed intra-arterial gas in the right vertebral artery, although the size of the injector tip was not reported. We use a 13-mm injector tip and recommend that the cervical artery be avoided. Chirchigilla et al.26 observed a case of embolism after intradiscal ozone injection, which was preferred over paravertebral administration. Intradiscal high dose O3/O2 gas injection is performed using fluoroscopy. Although complications are rare, intradiscal ozone injection can cause embolism and serious infection. In our study, similar improvements in pain scores were observed when paravertebral ozone injection was performed instead of intradiscal ozone injection. Paravertebral ozone injection carries no risk of embolism. It is important that a bacterial filter be fitted to the device used for sterilizing the injection area. Ozone doses over 40 μg/mL have toxic effects even if applied locally, so local injections should not be performed above this dose. Ozone is used for sterilization and we do not believe that ozone applied using a device with a bacterial filter is a potential source of infection.

Ozone therapy has been used for treating musculoskeletal diseases in recent years.27 Intramuscular ozone injections are normally used for long-term relief of lumbar back pain.1416 However, few studies have evaluated the efficacy of paravertebral ozone injection therapy for treating cervical disc diseases.1719

Ozone gas injection into the paravertebral muscle has been characterized as “chemical acupuncture,” where both the needle itself and the gas elicit a complex series of chemical and neurological reactions leading to a reduction in pain in the majority of patients with mild spinal pain.28 The gas rapidly dissolves in interstitial water and quickly reacts with antioxidants.

We found few studies in the literature of patients with neck pain treated using paravertebral ozone injections.17 Intradiscal ozone injections have been used most commonly for treating patients with cervical pain. Consoletti et al.17 explored the effectiveness of intramuscular paravertebral injection of O3/O2 in patients with chronic pain due to cervical bulging or herniated discs (cervicobrachialgy). They reported effective pain reduction in 29 patients. Beyaz et al.19 treated 44 patients who had chronic neck pain due to disc herniation with intradiscal ozone injections. In a follow-up analysis of their VAS pain scores, significant pain reduction was observed compared to the preoperative levels and no complications were reported.

It has been established that the ozone concentration should be between 18–25 μg/mL.25 We administered 20 μg/mL paravertebral ozone injections. There is no consensus optimal dose in the literature; Consoletti et al.17 did not specify the dose they used in their cervical paravertebral study, while Biazzo et al.16 used a 27 μg/mL dose and Özcan et al.12 administered 15 μg/mL lumbar paravertebral ozone injections.

The retrospective design and lack of any control group represent the limitations of this study, which aimed to demonstrate that cervical paravertebral ozone injection is an easy, effective and minimally invasive treatment for relieving the pain caused by disc disease and degeneration.

Table 1

Visual analog scale pain scores and Japanese Orthopedic Association scores of neck pain patients with cervical paravertebral O3/O2 injection

	Visual analog scale score	Japanese Orthopedic Association score
Pre-injection	8.5 ± 1.3 (5–10)	12.2 ± 3.2 (10–15)
2 mon after injection	3.5 ± 1.6 (0–6)	15.8 ± 2.2 (12–17)
6 mon after injection	4.0 ±1.1 (0–7)	16 ± 2.8 (13–17)
P1	0	0
P2	0	0
P3	0.459	0.344

Note: Data are expressed as the mean ± standard deviation (range), and were analyzed by Mann Whitney U test. P1: P value of comparing pre-injection and month 2 scores; P2: P value of comparing pre-injection and month 6 scores; P3: P value of comparing month 2 and 6 scores.