Transforaminal Epidural Steroid Injection Improves Neuropathic Pain in Lumbar Radiculopathy: A Prospective, Clinical Study
Keywords: Epidural injections, herniated disc, neuropathic painKey Message: TFESI is an effective and safe method to decrease not only nociceptive but also NP component in patients with chronic radiculopathy due to LDH.
Low back pain (LBP) is one of the most common and difficult-to-treat health problems in clinical practice worldwide., In about 40% of patients, LBP is associated with lumbosacral radioculopathy due to intervertebral disc herniation. To date, several pathophysiological mechanisms of chronic lumbosacral radiculopathy have been suggested and chronic LBP has been increasingly considered a mixed pain syndrome consisting of both nociceptive and neuropathic components.,,, Lumbosacral radicular pain is the most common form of neuropathic pain (NP). Majority of patients with neuropathic LBP experience increased pain, disability, anxiety, depression, and poor quality of life than those with nociceptive component.,, Therefore, clinical diagnosis of NP is of utmost importance to improve prognosis and to tailor effective treatment modalities.
Several studies have shown the short-term efficacy of transforaminal epidural steroid injection (TFESI) in the treatment of lumbosacral radiculopathy.,,, The TFESI is target-specific and is an effective option that delivers the agent to the ventral epidural space where pathological alterations are present., On the other hand, despite several studies showing the efficacy of TFESI in the treatment of lumbosacral radiculopathy, there is a limited number of studies investigating the role of TFESI in the NP component, and these studies lack in terms of homogeneous diagnoses.,, In addition, to the best of our knowledge, there is no study available evaluating the effect of NP on TFESI outcomes in patients with radiculopathy due to lumbar disc herniation (LDH).
In the present study, our hypothesis is that TFESI is effective not only in nociceptive component but also in NP of chronic radiculopathy due to LDH and that the presence of NP before the procedure is a possible risk factor that affects the TFESI outcomes. Therefore, our primary objective is to investigate the effect of TFESI on the NP component of chronic radiculopathy due to LDH. Our secondary objective is to evaluate the presence of NP before the procedure on TFESI outcomes.
This prospective, clinical study was conducted at Marmara University, Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Division of Pain Medicine between September 2018 and April 2019. All patients were informed about the nature of the study, and a written informed consent was obtained. The study protocol was approved by the Ethics Committee of Marmara University, Faculty of Medicine (No. 09.2018.592) (10.07.2018). The study was conducted in accordance with the principles of the Declaration of Helsinki.
The study population included a total of 61 patients who were admitted with LBP with unilateral pain radiating to the lower extremity, were unresponsive to the conservative treatment modalities, and were diagnosed with unilateral/unilevel radiculopathy due to LDH based on clinical sings, physical examination, and lumbar magnetic resonance imaging (MRI) findings. The patients were scheduled for single-level TFESI. Inclusion criteria were as follows: age 18–65 years; having LBP with unilateral pain radiating to the lower extremity for 3 months or longer and being unresponsive to conservative treatment modalities; patients who do not use medications (gabapentin, pregabalin, etc.) for neuropathic pain; having a Numeric Rating Scale (NRS) score of ≥4; clinical presence of unilateral lumbar radiculopathy on physical examination; and having LDH at L4-5 or L5-S1 levels with L5 or S1 spinal nerve root compression as evidenced by MRI within the past 6 months. Exclusion criteria were as follows: having bilateral symptoms or symptoms involving more than one segment; having previous lumbar surgery such as lumbar fusion or laminectomy; having transitional vertebrae, lumbar spinal stenosis, spondylolysis, spondylolisthesis, or scoliosis; having lumbar epidural steroid injection within the past 3 months; having a history of polyneuropathy or entrapment neuropathy; having bleeding diathesis; having systemic or local infections; having systemic diseases associated with peripheral nerve involvement such as ankylosing spondylitis, rheumatic diseases, or diabetes.
Sociodemographic characteristics of the patients including age, sex, and education status and duration of radiculopathy were recorded. The pain severity was evaluated using the NRS before the procedure and at 1 h, 3 weeks, and 3 months after the procedure. The Oswestry Disability Index (ODI) for functional status, the Beck Depression Inventory (BDI) for psychological status, and the Douleur Neuropathique 4 Questionnaire (DN4) for NP were used before the procedure and at 3 weeks and 3 months after the procedure. The DN4 contains seven items associated with characteristics of pain (burning, painful cold, electric shocks, tingling, pins and needles, numbness, itching) and three items associated with physical examination (hypoesthesia to brushing, hypoesthesia to fine tactile stimuli and brush-evoked allodynia). Each component is scored as present (1) or absent (0) and a score of ≥4 indicates NP.
The evaluation of level of pain, registry of demographic data, pre- and postprocedural follow-up, and treatment outcomes were performed by a single physiatrist. The TFESI was performed by a single pain medicine specialist with a minimum 10-year experience under the guidance of fluoroscopy. No treatment for NP was given to any patient or no medication (such as paracetamol and nonsteroid anti-inflammatory drugs) modification was done throughout the study period.
All patients were placed in the prone position and supported with a pillow under the abdomen to reduce lumbar lordosis. The injection site was cleaned up three times with povidone-iodine antiseptic and covered with a sterile dressing. The arm of the fluoroscopy was rotated obliquely by 10–30 degrees toward the region in the cranial direction, and the foramen was visualized. Local anesthesia (3 cc 2% prilocaine) was given to the skin and subcutaneous tissue. A Quincke 3.5-inch 22-gauge spinal needle was inserted under the intermittent guidance of fluoroscopy using the coaxial technique and advanced to the subpedicular space in the 6 o'clock direction. The needle position was confirmed through a lateral view. Following confirmation, 1–2 mL contrast dye was given the needle position in the epidural space, which was confirmed in anteroposterior and lateral views [Figure 1]. Once adequate flow of contrast dye was achieved without vascular flow, a mixture of 80 mg methyl prednisolone acetate, 1 cc physiological saline, and 1 cc (0.5%) bupivacaine was injected. Following the procedure, all patients were transferred to the observation room and monitored for 1 h. The patients without any postprocedural complications were evaluated at 1 h and discharged with recommendations.
Due to the lack of previous studies with similar designs, we were unable to calculate the sample size at the beginning of our study. All patients who met the inclusion criteria during the study period were included in the study. Post-hoc power analysis was performed to test whether the sample size of the study was adequate. For the calculation of the change in DN4 scores to determine neuropathic pain, which is the main hypothesis of the study, the study power was found to be 89%. Post-hoc power analysis was performed using the G*Power version 3.1 (Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany) software.
Statistical analysis was performed using the SPSS version 20.0 software (IBM Corp., Armonk, NY, USA). Continuous variables were expressed in mean ± standard deviation, median (interquartile range [IQR] 25th—75th), and categorical variables were expressed in number and frequency. The Chi-square, Mc Nemar, and Cohran Q tests were used to compare categorical variables, where applicable. The Kolmogrov–Smirnov test was used to analyze normal distribution of quantitative data. For the comparison of non-normally distributed data, the Mann–Whitney U, Wilcoxon, and Freidman tests were used, while the independent t-test was used to compare normally distributed data. A P value of <0.05 was considered statistically significant.
Of a total of 61 patients, 58 completed the follow-up. Among them, 33 were males and 25 were females with a mean age of 41.6 ± 11.1 years. The median symptom duration was 4 months. The TFESI procedure was applied at the foraminal level of L5-S1 to 32 patients (55.2%) and at the foraminal level of S1–26 patients (44.8%). During the injection, vasovagal reaction occurred in two patients. No major complication was seen during or after the procedure in the remaining patients.
At baseline, 35 patients (60.3%) had NP [Table 1]. The number of female patients with NP was significantly higher than male patients (P = 0.034). However, there was no significant difference in the NP rate between male and female patients in terms of other sociodemographic characteristics [Table 2].
There was a significant change from baseline in the NRS, ODI, BDI, and DN4 scores in all patients at all timepoints (P < 0.05) [Table 3] and [Figure 2]. The number of patients with NP as assessed by the DN4 was 35 (60.3%) before the procedure, 21 (36.2%) at 3 weeks, and 23 (41.2%) at 3 months, indicating a statistically significant difference between the pre- and postprocedural scores (P = 0.001).
Treatment responses were similar between the patients with and without NP at all timepoints (P > 0.05). However, the ODI scores were significantly higher at 3 months in the patients with NP than those without NP (P = 0.013). The BDI scores at baseline, 3 weeks, and 3 months were also significantly higher in the patients with NP than those without NP (P < 0.001, P = 0.016, and P = 0.016, respectively) [Table 4].
In the present study, we evaluated the effect of TFESI on NP component of pain in patients with chronic radiculopathy due to LDH and to investigate whether NP was a risk factor for poor treatment outcomes. Our study results showed that the majority of the patients (n = 35) had NP at baseline and there was a significant decrease in the number of patients with NP and DN4 scores following TFESI at all timepoints. In addition, there was a significant decrease in the NRS, BDI, and ODI scores at all timepoints. The ODI scores were significantly higher at 3 months, and the BDI scores at baseline, 3 weeks, and 3 months were also significantly higher in the patients with NP than those without NP. These findings indicate that TFESI is effective to decrease not only nociceptive but also NP component in patients with chronic radiculopathy due to LDH, which support our hypothesis that NP is a risk factor for poor treatment outcomes.
Herniated nucleus pulposus is associated with inflammation and ectopic firing of the dorsal root ganglia and spinal nerves. Ectopic firing is characterized by increased glial activity of the spinal cord and release of pain-modulating substances by active glial cells that play a role in the development and maintenance of central sensitization-related neuropathic pain. The TFESI exerts its anti-inflammatory effect on NP by reducing cytokines and chemokines, reducing inflammation of the dorsal root ganglia, spinal nerve, and epidural space and by inhibiting or decreasing the neuroglial activation and by stabilizing the neuronal membranes and suppressing nociceptive C fibers and ectopic discharges in the affected nerve., These pathophysiological mechanisms might have played a role in the development of NP component of the pain in nearly two-thirds of the patients with chronic radiculopathy due to LDH in our study. In addition, the decline in the number of patients with NP and DN4 scores in all timepoints can be attributed to these effects of TFESI on NP.
Despite a relatively low number of researches, previous studies investigating the effect of TFESI on NP component of chronic LBP have shown similar results to our study.,, In their study, Batistaki et al. reported a significant improvement in the DN4 scores at six months of follow-up after TFESI in patients with radicular back pain. In another study, Sari et al. evaluated the effect of TFESI on NP and quality of life in patients with chronic LBP and showed a significant improvement in the DN4 scores at 3 months. In addition, Rados et al. investigated the effectiveness of TFESI versus interlaminar epidural steroid injection in patients with chronic unilateral lumbar radiculopathy and reported a statistically significant decrease in the NP component at 6 months in both groups. However, unlike our study, the aforementioned studies included patients with not only LDH, but also spinal stenosis and even failed back surgery with multiple number of spinal nerve roots affected. In our study, only patients with unilateral/unilevel radiculopathy due to LDH were included.
In the present study, we found significantly higher ODI scores at 3 months and significantly higher BDI scores at baseline, 3 weeks, and 3 months in the patients with NP than those without NP. This finding is consistent with previous studies reporting higher pain severity, disability, anxiety, and depression and worse quality of life in patients with LBP than nociceptive LBP.,, The relatively low response to treatment among NP patients than non-NP patients can be attributed to the underlying mechanisms of NP that plays a role in the development and chronicity of pain including cornus of the spinal cord, structural changes in the interneurons and glial cells, glial activation-induced central sensitization. In addition, it has been estimated that treatment-related cost of neuropathic LBP is ~70% higher than nociceptive LBP. Therefore, the evaluation of NP component is critical to establish effective treatment modalities, to increase treatment success, and to reduce treatment-related cost in patients with chronic lumbar radiculopathy. Our study results showed that TFESI was an effective method to reduce NP component in patients with chronic radiculopathy due to LDH. However, the present study lacks a control group due to ethical considerations and there is still a need for further prospective, randomized-controlled, head-to-head studies to establish a definite conclusion on the effect of TFESI on NP.
In the literature, several studies have utilized the DN4 for the evaluation of efficacy of treatment modalities in patients with chronic LBP and NP.,,,, The DN4 is a valid tool that discriminate between NP and nociceptive pain in chronic LBP., It is a clinician-administered questionnaire with 83% sensitivity and 90% specificity in identifying the NP component. Consistent with previous studies, we also utilized DN4 in our study for the evaluation of the NP component in patients with chronic radiculopathy due to LDH. However, although DN4 is a useful tool, about 20–30% of patients may be missed with this questionnaire. In addition, it does not provide any information regarding the severity of NP.
Previous studies have demonstrated that 12–55% of patients with chronic LBP have the NP component. In contrast, 60.3% of our patients had NP at baseline. The higher rate in our study population than previous studies can be explained by the discrepancy in the evaluation criteria used, personal and sociocultural characteristics of patients included, and chronic LBP etiologies. Furthermore, the number of female patients with NP was significantly higher than male patients. Similarly, previous studies evaluating the NP component in chronic LBP patients reported similar results.,, Our study results are, therefore, consistent with the literature. Nonetheless, further large-scale epidemiological studies are required to gain a better insight into the NP prevalence and true effect of sex in this patient population.
In a study including 30 patients with radiculopathy due to LDH, Roy et al. reported a significant improvement in the NRS and Roland-Morris Disability Questionnaire scores at 6 months compared to baseline. In another study, Ahadian et al. showed a significant improvement in the ODI scores at 3 months following lumbar TFESI. In a comprehensive literature review, Benny and Azari. found strong evidences for TFESI in the treatment of lumbosacral radicular pain for both short- and long-term relief. Despite the lack of long-term efficacy results, our study showed a significant improvement in the NRS and ODI scores at 3 months, consistent with previous studies.
The main strength of this study is that, to the best of our knowledge, this is the first to investigate the effect of NP component on TFESI outcomes in patients with chronic radiculopathy due to LDH. It has also a prospective design with a homogeneous sample. However, the lack of long-term results and the fact that some of the patients might have been missed with DN4, despite high sensitivity and specificity, can be regarded as the main limitations.
In conclusion, our study results suggest that TFESI is an effective and safe method to decrease not only nociceptive but also the NP component in patients with chronic radiculopathy due to LDH. Clinicians should keep in mind that NP is a risk factor that adversely affects the TFESI success and patients should be evaluated before the procedure to identify those most likely to benefit from treatment.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]