Therapeutic Periradicular Injections: It’s a Gas!

Radiology departments and imaging centers nationwide are experiencing an increased demand for image-guided spine injection procedures. The use of spine injections for diagnosis and treatment of neck, back, and radicular pain has gained increased popularity with the advent of advanced imaging technology, an increased understanding of the pathophysiology of pain, the demand for less-invasive interventions, and demographic factors. Most individuals will experience neck and low back pain during their lifetime, and with increased age comes a greater number of potential patients with these symptoms.

Therapeutic spinal injections have been performed for more than half a century, and for more than 3 decades selective nerve root injections have been performed for the evaluation and treatment of patients with radicular pain or failed spine surgery. Nerve root injections can be performed for diagnostic preoperative evaluation, to confirm imaging findings, or to solve discrepancies between imaging and clinical findings. Selective nerve blocks and transforaminal epidural injections are also performed for pain management. Local anesthetic and steroids are administered to target the biochemical factors that result in nerve irritation and enhanced nociception. The mechanism for pain relief following steroid administration in this fashion is attributed to its anti-inflammatory effects. By inhibiting the production of phospholipase A and other substances that cause perineural inflammation and pain generation, anti-inflammatory substances suppress the local biochemical cause for pain due to disk degeneration. Steroids also inhibit the activity of nociceptive C fibers, which suppresses the transmission of pain impulses to the CNS. The prolonged therapeutic effects of these blocks may keep the patient pain free for weeks to months. This can result in delay or possible avoidance of surgery.

In this issue of AJNR, Bonetti et al report a prospective blinded study comparing intraforaminal infiltration of O₂/O₃ versus periradicular steroid injections for lower back pain. They compared the short-, medium-, and long-term outcome of patients with lower back pain and radicular symptoms. The patients were stratified into two groups, those with pain attributable to primarily disk disease and those with nondiskogenic spinal column degenerative changes. The authors found that patients in both groups responded very well to both modalities (ozone and steroid administration) at short-term follow-up; however, they describe a statistically significant long-term advantage in the ozone therapy group versus the steroid recipients. Bonetti et al postulate that the benefits of the ozone injections are linked to the inhibition of E2 prostaglandins and A2 phospholipase, similar to the therapeutic effects of steroids.

There is a paucity U.S. literature regarding the use of ozone as a therapeutic agent for spinal injections. Several articles appear in the European literature, but many are in obscure journals and do not represent randomized controlled studies. The mechanism of action for the relief of radicular pain may be attributable to one of several biochemical actions exhibited by ozone. Among these, analgesic and anti-inflammatory effects are probably the most important. Additional chemical properties of ozone have been described, including enhancement of glycolysis, hematologic effects, and even bactericidal, fungicidal, and virustatic effects. These mechanisms of action were reviewed in an investigation published last year in the AJNR (1). Andreula et al evaluated the effects of intradiskal ozone alone versus an adjunctive periradicular steroid injection. Animal studies have confirmed the offect of ozone on cytokine production (2). There are additional therapeutic mechanisms of action that are currently being investigated. These include localized improvement of microcirculation, resolution of venous stasis, and the direct effect of ozone on mucopolysaccarides associated with herniated disks.

The diverse affects of ozone are dependant on the concentration, or relative strength of the preparation, which have been studied by using animal and cadaveric investigations. The dose-dependent behavior of ozone mixtures mandates accurate photometric control and the production of precise ozone concentrations for any equipment used for medical purposes. Unfortunately, this is difficult to confirm when reviewing the literature, and published values must evaluated in light of the technique and quality of instrumentation.

CT-guided injections were used for all patients in Bonetti et al’s series. A brief comment on technique selection is warranted. Proponents of CT guidance for injection procedures cite advantages including the ability to monitor adjacent structures and confirm precise needle tip location. On the other hand, unlike real-time fluoroscopic monitoring with contrast administration, CT does not allow real-time assessment for intravascular injections, which cannot be excluded on the basis of negative aspiration. Assessing for vascular infiltration is extremely important when injections are performed in the upper lumbar or lower thoracic distribution, potential locations for the artery of Adamkiewicz. In the cervical region, radicular vessels that contribute to perfusion of the spinal cord may also be encountered within the intervertebral foramina. Injection of particulate steroids into these vessels may result in cord infarction and other disastrous outcomes. Direct injection of a particulate steroid suspension or a gas (O₂/O₃) may present the risk of embolization if inadvertent intravascular injection occurs. It is extremely important to be aware of these anatomic considerations when performing transforaminal injections. If O₂/O₃ gas is administered, a slow injection of <10 mL (combined disk and foramen) is recommended to avoid complications (Dr. Mario Muto, personal communication). Another technical consideration is the use of contrast (with CT or fluoroscopy), which maps the subsequent distribution of therapeutic substances.

We would welcome further innovations and techniques (many of which are already popular in other countries) as potential solutions to clinical challenges. On the other hand, we must bear in mind an important axiom for all physicians: “primum non nocere” (first, do no harm). It is important to document efficacy and safety before employing any new treatment technique. All treatment modalities should thus undergo well-designed controlled investigations (control for natural history of the condition being treated). Although this novel approach to the treatment of back and radicular pain looks promising, there are a number of important issues that plague ozone’s proponents (3). These include a lack of standardized procedures and dosages, problems with calibrations for confirming those dosages (because of variable fidelity of equipment), incomplete understanding of the precise mechanism of action, inherent difficulties by using a gas as a therapeutic substance, and a lack of controlled trials. Further, ozone exposure has been linked to a number of adverse health effects (4). Bonetti et al have moved us closer to addressing a number of these issues, and we look forward to further investigations of this technique.

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