Anesth Analg 2003;97:828-832
© 2003 International Anesthesia Research Society
PAIN MEDICINE
Can Quantitative Sensory Testing Predict the Outcome of Epidural Steroid Injections in Sciatica? A Preliminary Study
Elad Schiff, MD*, and
Elon Eisenberg, MD
*Department of Internal Medicine B, Bnai-Zion Medical Center and
Pain Relief Unit, Rambam Medical Center, and the Haifa Pain Research Group, the Technion, Israel Institute of Technology, Haifa, Israel
Address correspondence and reprint requests to Elad Schiff, MD, Department of Internal Medicine B, Bnai-Zion Medical Center, P.O. Box 4940, 31048, Haifa, Israel. Address e-mail to drschiff{at}actcom.net.il
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Abstract
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Quantitative Sensory Testing (QST) is a psycho-physiological test used to identify dysfunction of individual nerve fiber types. In the present study, we investigated whether selective nerve fiber dysfunction, as assessed by QST, correlates with the effectiveness of epidural steroid injections (ESI) in patients with lumbar radiculopathy. Twenty patients with unilateral painful sciatica caused by disc herniation participated in this open study. Before ESI, quantitative thermal and mechanical sensory testing was conducted at the most painful dermatome and the contralateral dermatome. The primary outcome measure used was the self-recording of pain intensity twice daily with a 0–10 numerical pain scale (NPS). Secondary efficacy measures included the Short Form of the McGill Pain Questionnaire, the straight leg raising test, and the lumbar range of motion. A significant difference in all types of sensory thresholds between the affected and the contralateral dermatomes was detected at baseline. All outcome measures improved subsequent to the ESI. A significant positive correlation was found between the increase in cold sensation thresholds of the affected dermatome (A
-fiber dysfunction) and the improvement in NPS. The increase in touch and vibration thresholds (Aß-fiber dysfunction) was found to be inversely correlated with the improvement in NPS. No correlation was found between heat sensation thresholds (C fibers) and any of the outcome measures. These results suggest that QST has the potential to be an important tool in the selection of the appropriate treatment (e.g., ESI versus surgery) for patients with sciatica and may assist in identifying the mechanisms of pain generation in these patients.
IMPLICATIONS: Quantitative sensory testing has the potential to become an important tool in the selection of appropriate treatment for lumbar radiculopathy and to assist in identifying the mechanisms of pain generation in these patients.
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Introduction
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Lumbar radiculopathy secondary to prolapsed disk is a relatively common medical condition. Nevertheless, the precise pathogenesis and the best treatment modality for sciatica have not been clearly defined. It has been believed for decades that nerve root compression by the protruded intervertebral disk is the main cause of sciatic pain (1). Yet, the frequent lack of correlation between the severity of symptoms and the size of the herniated disk has suggested the potential presence of additional underlying mechanisms (2). There is evidence that leakage of inflammatory substances from the nucleus pulposus can cause inflammation, nerve root excitation, and pain (3). However, it is difficult to say which of the two is the dominant mechanism in any given patient.
Epidural steroid injections (ESI) are frequently administered for symptomatic treatment of sciatica, although the efficacy of this procedure has not been established, and its benefit seems to be only of short duration (4,5). This is in part because of the absence of clinical criteria or guidance for the selection of patients who are most likely to benefit from such treatment (6). The lack of solid clinical guidance for patient selection can be explained by the fact that neither the pathogenesis of sciatica (compression versus inflammation) nor the mechanisms by which epidural steroids produce their analgesic effects have been elucidated.
Quantitative Sensory Testing (QST) is a psycho-physiological test used to measure the thresholds for different sensations (7). Heat sensation threshold reflects the unmyelinated C-fiber function, cold sensation threshold reflects the thinly myelinated A-fiber function, and vibration threshold reflects the thickly myelinated Aß-fiber function. Because the function of Aß fibers is more likely to be affected by compression than that of A and C fibers (8), the degree of dysfunction of the individual fiber types measured by the QST may identify the dominant mechanism of injury (compression versus inflammatory) in patients with sciatica induced by a prolapsed disk (9). Several other studies have used QST to demonstrate selective nerve fiber dysfunction in sciatica (10–12). Furthermore, a correlation between QST findings and clinical outcome after disk surgery in patients with sciatica was reported in one study (12). However, the usefulness of QST as a possible predictor of ESI outcome has not been tested.
The aim of the present open study was two-fold: (a) to identify the type of nerve fibers affected in sciatica, based on the QST, and (b) to identify correlations between the degree of nerve fiber dysfunction and ESI outcome, thereby improving the ability to select only those patients who are most likely to benefit from the procedure.
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Methods
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The study population consisted of patients with sciatica who were referred, primarily by orthopedic surgeons, to the Pain Relief Unit in Rambam Medical Center, Haifa, Israel, for pain control. Consecutive patients aged 18–70 yr were enrolled in the study after meeting the following criteria: (a) painful lumbar radiculopathy, confined to a single dermatome, of 1- to 24-mo duration and (b) presence of a herniated disk, confined to the spinal canal, as per imaging studies (computed tomography, magnetic resonance imaging, or both) correlating with the clinical picture in terms of level and side. Subjects with pregnancy, diabetes, a history of back surgery, previous ESI, or other pain syndromes were excluded. A written informed consent was obtained from all patients. The study was approved by the hospital’s ethics committee.
Patients who met the above inclusion criteria were assigned to receive an ESI subsequent to a 1-wk baseline period. The ESI consisted of 80 mg of methylprednisolone (Depo-Medrol, Upjohn, Belgium) diluted in 5 mL of 0.9% NaCl to a total volume of 7 mL. It was performed with a 16-gauge Tuohy needle using the loss-of-resistance technique at the level of pathology. Patients were seen at the clinic before the procedure for assessment of nerve fiber dysfunction (QST and Von Frey) and for baseline pain measurements. Follow-up clinic visits were held 2 and 4 wk subsequent to the procedure. No concurrent treatments were allowed during the study period, with the exception of as-required rescue doses of simple analgesics (paracetamol or dipyrone).
Quantitative vibration and thermal thresholds were determined with the method of limits on a Medoc TSA-2001 device (Medoc, Israel) (13). For the detection of thermal thresholds, a Peltier thermode, size 30 x 30 mm, was attached to the skin. Stimulator temperature range was 0°C–50°C, and skin adaptation temperature was a constant 32°C. Increasing stimuli were applied, directed from the adaptation temperature toward the sensation range at a temperature change rate of 1°C/s. Subjects were asked to depress a switch at the instant they perceived a specific sensation (e.g., cold sensation). At each site, three readings were obtained for each thermal sensation, and their average was determined as the threshold score. Threshold for vibration was measured in a similar way, with a constant probe pressure at a vibration frequency of 100 Hz and increasing amplitude in increments of 0.8 µm/s. The average of three consecutive readings was noted as the detected threshold. Mechanical touch thresholds were measured by applying graded punctate stimuli to the skin using a set of 15 nylon filaments of varying bending pressure (von Frey filaments). The series of filaments represents stimuli from 10 mg to 300 g. The weakest stimulus that the patient identified two of three stimulus applications was recorded as the perception threshold. All tests were performed by one examiner (ES). Before assessing the quantitative vibration and thermal thresholds, a training run was given (first) at the thenar eminence of the nondominant hand. Tests were performed at the most painful site in the affected dermatome, followed by threshold measurement at the contralateral dermatome.
Patients were required to keep a record of their daily pain level, as measured on a 0–10 numerical pain scale (NPS) twice daily during the week before and the 4 wk subsequent to the ESI. The weekly average of the NPS was regarded as the primary outcome measure (14). Three office visits were held throughout the study period, wherein spontaneous pain was measured with the Short Form of the McGill Pain Questionnaire (SF-MPQ) (15). The Straight Leg Raise (SLR) test was used to measure evoked sciatic pain with a manual goniometer, recording the angle at which the patient reported an increase in pain as a result of the maneuver. Range of motion of the lumbar spine (leaning to the affected side) was also measured with a manual goniometer.
Statistical analysis was performed with SAS (SAS Institute, Cary, NC). NPS results were averaged across the number of weeks and analyzed by repeated-measures analysis of variance (ANOVA). Comparisons of the baseline week to each subsequent week were performed with Dunnett test. Differences in thresholds between the affected and nonaffected sides were assessed by mixed-model ANOVA and were defined as 
. Results are considered significant at the 0.05 level (P value), and the data are presented as mean ± SEM. Stepwise regression analysis was used to evaluate the most significant QST variable influencing pain reduction. To apply the stepwise regression, the mixed model was used (i.e., combined backwards and forwards variable entry). The pseudo P value used as the point for entrance and exit from the model was 0.25 in both cases.
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Results
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All 20 participating patients, including 11 men and 9 women, completed the study. Their median age was 41 yr, with an age range from 24 to 62 yr. The median duration of their symptoms was 7 mo, with a range of 2–24 mo. The most common level of radiculopathy was at the L5 dermatome (9 patients), followed by the L4 dermatome (7 patients), and the L3 and S1 dermatomes (2 patients each). It is noteworthy that all patients had well-characterized unilateral sciatic pain and had no other types of pain.
The baseline pain variables are indicative of significant pain and substantially impaired mobility. The mean baseline NPS (the primary outcome measure) was 5.7 ± 0.4, and the SF-MPQ score was 20.0 ± 1.3. The baseline SLR in the affected limb was 46.0 ± 3.8 degrees, and the baseline bending towards the affected side was 37.2 ± 2.7 degrees.
Table 1 summarizes the differences in thresholds (S) of the four tested modalities between the affected and the nonaffected legs. All thresholds were significantly increased in the affected side, indicating mechanical and thermal hypoesthesia.
The effect of the ESI on the weekly NPS is shown in Figure 1. Mean spontaneous pain (as measured on the NPS) decreased from the baseline measurement of 5.7 ± 0.4 to 4.6 ± 0.4 by the end of the follow-up period. This decrease was statistically different from the baseline measurement at Weeks 2, 3, and 4 (Fig. 1). When translated to percentage of reduction in pain, the procedure resulted in a mean decreased of 22.7% ± 6.9%. The range of improvement varied considerably: 6 subjects had more than 50% improvement; 2 showed a 25%–50% improvement, and 10 showed a 0%–25% improvement. Two patients had worse pain (-10% and -61%) at the end of the follow-up period. The SF-MPQ score decreased from 20.0 ± 1.3 to 15.2 ± 1.3. A small yet statistically significant improvement was also noted in the SLR and in the range of motion of the lumbar spine (approximately 4 degrees each). Table 2 summarizes the effects of the procedure on the secondary pain measures. No adverse events were recorded.
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Figure 1. Change in numerical pain scale (NPS) (mean ± SEM), as documented from 1 wk before epidural steroid injections (ESI) (baseline) and continuing for the 4 wk subsequent to it. P represents the difference between the baseline week and each of the four subsequent weeks (*P < 0.05; **P < 0.005; ***P < 0.0001).
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The exploratory stepwise regression analyses suggest varying degrees of relationship between the baseline QST variables and the improvement in outcome measures (Table 3). The improvement in the primary outcome measurer, the NPS, shows a direct correlation with cold sensation threshold. In contrast, the improvement in the NPS shows a negative correlation with touch and vibration thresholds. The improvement in the secondary subjective outcome measurer, the SF-MPQ score, correlates only with the mechanical thresholds ( vibration and touch) but in two different directions. It directly correlates with vibration threshold and inversely with touch. The objective variables show a direct correlation between the improvement in the SLR and cold sensation threshold as well as a direct correlation between the improvement in bending and the touch threshold. It is noteworthy that the relationships between the improvement in the objective variables and the threshold abnormalities have much larger pseudo P values compared with those of the subjective variables (Table 3). This indicates that these correlations are much weaker. Interestingly, heat sensation thresholds do not correlate with any of the outcome measures.
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Discussion
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The diagnosis of lumbar radiculopathy induced by a herniated disk is usually straightforward. Patient history, physical examination, imaging studies, and, occasionally, electrophysiological tests can establish the diagnosis in most patients. Yet, the treatment of sciatica is controversial (4–6), and selection of the best treatment for an individual patient remains a clinical challenge. This is, in part, because the pathophysiology of sciatic pain is not fully understood.
Until recently, it was believed that spinal nerve root compression was the main cause of sciatic pain. This notion was based, in part, on histopathological studies of tissues taken from humans with radiculopathy, in whom a decreased number of large myelinated fibers was observed (16,17). It was further supported by the fact that heavily myelinated nerve fibers are the first to be damaged as a result of peripheral (8,18) and spinal nerve root compression (19).
In contrast, the results of the present study suggest that different types of nerve fibers are affected in patients with radiculopathy. The increased heat, cold, and mechanical thresholds in the affected dermatome, as compared with the contralateral dermatome, are likely to be indicative of impaired function of unmyelinated, thinly myelinated, and heavily myelinated fibers, respectively. Our findings are consistent with those of Nygaard et al. (10), who reported increased heat, cold, and mechanical thresholds in the affected dermatome. Mosek et al. (11), who tested only the thermal thresholds, found a significantly increased threshold only for cold sensation in the affected dermatome of the symptomatic leg, as compared with controls. However, Zwart et al. (9) found significantly increased warm and cold sensation thresholds on the affected side compared with the nonsymptomatic side.
The findings of the present and of previous studies (9–12) that small myelinated A fibers and unmyelinated C fibers are also affected can shed new light on the pathophysiology of sciatic pain by indicating that spinal nerve root compression is not the only mechanism underlying sciatica. One possible other mechanism is nerve root inflammation caused by leakage of inflammatory substances from the ruptured nucleus pulposus (3).
ESI is a common mode of treatment for lumbar radiculopathy. It is true that the long-term efficacy of this procedure has been debated for many years, but there is evidence justifying its use for at least short-term relief of sciatic pain (4–6). For this reason, we chose to use only a short-term follow-up period, i.e., four weeks, in the present study. Although not designed as a controlled trial, this study also suggests that the procedure can result in short-term pain reduction (as indicated by a mean of 23% reduction in NPS and 25% reduction in SF-MPQ scores).
However, consistent with the results of multiple other ESI studies, our results demonstrate a large between-patient variability in terms of the magnitude of the analgesic effect. One possible explanation for the heterogeneity of ESI outcome is attributed to the injection technique. It has been suggested that lack of fluoroscopic guidance can result in needle misplacement in a considerable percentage of patients who undergo ESI (20). Because other authors suggest the opposite (21), it is likely that controversy will continue to surround these imaging-guided techniques until large, double-blinded studies become available (22). Yet, it is noteworthy that even when performed under fluoroscopy, the outcome of ESI still demonstrates a large variability between patients (23), indicating that needle misplacement per se is not the only reason for outcome heterogeneity.
A different possible explanation is related to the variability in the size of the herniated disk and in the degree of nerve root compression. However, we found no evidence suggesting that a larger herniated disk is less likely to respond to ESI or vice versa (2). Furthermore, patients can respond to ESI without proven change in the degree of mechanical compression (24). This leads us to a third explanation, which is related to the two possible mechanisms by which ESI can exert analgesia in sciatica. First, steroids can lessen the compression caused by the herniated disk and reduce neural edema. Second, they can reduce the amount of inflammation around the nerve root. Thus, by correlating between the magnitude of spontaneous pain reduction induced by ESI and the type of nerve fibers affected, our pilot study may suggest that when nerve root compression, as indicated by impaired function of Aß fibers, is dominantly present, ESI is less likely to be effective. In contrast, when the thinly myelinated A fibers, which are less affected by compression, are dominantly affected, ESI will be more effective.
The idea that the degree of dysfunction of different classes of nerve fibers can serve as a prognostic factor for treatment outcome has been tested. Nygaard et al. (12) have demonstrated that increased heat sensation threshold (damage to C fibers) before surgery can have a negative prognostic value for the success of microdiscectomy in patients with lumbar radiculopathy secondary to prolapsed disk. Taken together, the results of these two studies may suggest that QST could be used as a tool in the algorithm of sciatic pain treatment. This study shows that patients with a more severe injury to A fibers will have a more favorable response to ESI, whereas those with a more severe injury to large fibers will benefit from decompression. This suggested algorithm requires further confirmation by large-scale controlled trials.
Although the magnitude of spontaneous pain reduction caused by ESI seems to directly correlate with the degree of A-fiber dysfunction and to inversely correlate with Aß-fiber dysfunction, several caveats are required to place these results in context. First, these correlations were significant between the QST and the NPS as well as the SF-MPQ scores but not with the SLR or with the range of motion measures. In our view, the correlation with the primary outcome, the NPS, is the most important one because this is the only variable that was measured continuously, day-by-day, throughout the entire study period. All of the other variables were measured only at three time points, two weeks apart from each other. Furthermore, the minor improvements detected in mechanical outcome (approximately four degrees) are probably too small to show any significant correlations with the independent variables. Second, the fact that A-fiber, but not C-fiber, dysfunction correlated with the improvement in NPS is puzzling, especially in light of the hypothesis that inflammation rather than compression is likely to respond better to ESI. We do not have a clear explanation for this finding.
In summary, it seems that QST may become an important tool in the decision-making process for the treatment of lumbar radiculopathy. If further studies confirm our findings, then the use of QST, in addition to clinical signs and symptoms, has the potential to become a powerful tool in the selection of the appropriate treatment (e.g., ESI versus surgery) for patients with sciatica.
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Acknowledgments
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Supported, in part, by the independent research fund of the Pain Relief Unit at Rambam Medical Center (No. 00171).
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Accepted for publication May 7, 2003.
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Abstract
Introduction
