Immediate Pain Response Does Not Predict Long-Term Outcome of CT-Guided Cervical Transforaminal Epidural Steroid Injections

Discussion

Image-guided CTESI has been demonstrated to significantly reduce pain and improve function in patients with radicular pain syndrome.^1,3⇓–5,8 Patients are typically assessed immediately after epidural injections whether the procedure is completed by means of the CT-guided or fluoroscopic-guided approach. As clinicians, we often encourage our patients that improvement immediately after the procedure brings hope of long-term relief. However, there is little literature to support this contention, and, theoretically, the only effect immediately after the procedure should be the anesthetic effect. A significant decrease in the index pain after the procedure may be diagnostic, indicative that the appropriate level has been treated, and it may be predictive of surgical outcomes.⁷ However, it does not necessarily predict a long-term pain response or functional improvement after corticosteroid injection.

Though this study reaffirmed results of previously published data that CT-guided CTESI is effective, the results also demonstrated that immediate postprocedure pain response did not correlate well with long-term outcomes as measured by VNPS or RMDI. In contrast, the 2-week VNPS had a correlation with the long-term response at 2 months for VNPS and RMDI outcomes. Univariate logistic regression also defined that the 2-week VNPS would be a predictor of patients achieving a >50% improvement at 2 months (Table 4). To be clear, the immediate postprocedure pain response did not predict outcomes, but the 2-week VNPS was a significant predictor of patients who would maintain a >50% improvement. The results of this analysis also show that the higher the 2-week pain score, the less likely the patient is to achieve >50% relief at 2 months. The odds ratio of 0.789 indicates that on average, a patient would have 2.6 times better odds of achieving the 50% improvement than a patient with a 4-point higher baseline VNPS.

As with the VNPS, the 2-week RMDI score also was a significant predictor of patients who would have a sustained 50% improvement in RMDI at 2 months. Collectively, the data show that clinicians should be cautioned against making predictions of patient outcomes based on the immediate response to the cervical injection. The patient result observed after 2 weeks is a much stronger predictor of the longer-term outcome at 2 months for pain response and functional improvement. The odds ratio of 0.853 indicates that on average, a patient would have 1.9 times better odds of achieving the 50% improvement than a patient with a 4-point higher baseline RMDI.

The poor correlation between the immediate postprocedure pain score and the long-term outcomes is not necessarily surprising. Though the 2% lidocaine used in this study may be able to temporarily decrease the cervical radicular pain through its direct effect on the sensory nerve fibers, and studies have shown that it can decrease leukocyte response,^9,10 it likely has minimal direct effect on the inflammatory cascade thought to be partially responsible for pain generation in radicular pain. The etiology of radicular pain is probably multifactorial and involves multiple mechanisms that cannot be immediately ameliorated with anesthetics or steroids.

Though Mixter and Barr¹¹ demonstrated that sciatica was associated with disk herniation in 1934, recent research has demonstrated that radicular pain is not only caused by mechanical injury but also by chemical inflammatory factors.^{12⇓⇓⇓⇓–17} These findings are substantiated by clinical findings such as asymptomatic prominent disk protrusions, radicular pain without mass effect on a nerve, and trials demonstrating improvement in pain without surgical decompression.^{18⇓⇓–21}

One significant cause of radicular pain is the inflammatory response that is present at the treatment level. Indeed, the anti-inflammatory properties of steroids are a major rationale for these injections.^12,22 There are many mediators that can generate an inflammatory response. High levels of phospholipase A2 are found in the intervertebral disk, and elevated levels of PLA2 have been found in tissues from human radiculopathy patients¹⁷ and animal models.¹⁶ PLA2 initiates the arachidonic acid cascade that leads to the production of prostaglandins, thromboxanes, and leukotrienes, all inflammatory mediators.^12,22 Inflammatory mediators, in turn, cause a range of effects including recruitment of immune cells (leukocytes, lymphocytes, macrophages, platelets, and mast cells) and the subsequent activation of these cells, edema through effects on the vasculature, and production of inflammatory cytokines among others. The inflammatory response can cause additional tissue injury, including Wallerian degeneration. This cascade also can increase pain through hypersensitization of the neural roots to stimuli that may not normally be painful.^12,22

The transforaminal injection of steroids can be effective by interacting with the inflammatory response at several points. A primary target of the steroid is the inflammatory cascade, particularly the effects of phospholipase A2 and the lipoxygenase pathway, thus reducing the downstream production of inflammatory mediators. Steroids also can reduce recruitment of leukocytes, capillary permeability, and edema; reduce the release of damaging mediators from activated leukocytes; and directly reduce the activity of pain pathways. Interruption of these cascades occurs over a period of days; thus, the effect of steroids is not immediate but becomes manifest over the days and weeks after treatment.

Given the complexity of the physical and inflammatory mechanisms that can be involved in causing radicular pain, it should not be surprising that a time point that allows the steroid effect to become manifest would be a better predictor of later outcomes for the patient. In this study, the 2-week pain and RMDI scores significantly correlated with the latter 2-month outcome, whereas the immediate postprocedure pain scores did not. The statistical analysis also shows that the lower the pain and RMDI scores at this 2-week time point, the higher the likelihood that this positive effect will persist at the 2-month time point. Though we as clinicians would like to offer patients hope on the basis of the anesthetic effect at the time of a procedure, ultimately we must counsel them that the true predictor of long-term relief will come once the steroids have been given time to have a localized effect on the nerves and surrounding tissues.

This study is limited by several factors. Study participants were referred for injection by use of a synthesis of multiple criteria including history and physical examination, imaging, and electromyography. This inevitably leads to heterogeneity in a population. Duration of pain and level of radiculopathy were not stratified. Further studies may be necessary to define whether a more limited patient cohort would affect outcomes. Loss to follow-up was expected; however, it may be a potential source of bias, as previously reported.⁵ Baseline VNPS and RMDI were not significantly different between the groups of patients with and without 2-week data. Further analysis of those lost to follow-up revealed that 2-week outcome was not associated with 2-month loss to follow-up, but baseline VNPS/RMDI was higher in those lost to follow-up at 2 months. This may conservatively bias our reported proportions of favorable response because the group of 2-month 50% responders had higher baseline RMDI than 50% nonresponders; therefore no missing data adjustments are made. Finally, all of these patients underwent CT-guided procedures. These results are probably transferable to fluoroscopic-guided cervical transforaminal epidural injections, but this cannot be ensured without a definitive study in that image-guided group.