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Early Thoracic Sympathetic Block Improves the Treatment Effect for Upper Extremity Neuropathic Pain

Yoo, Hyung Seok, MD*; Nahm, Francis Sahngun, MD; Lee, Pyung Bok, MD; Lee, Chul Joong, MD

doi: 10.1213/ANE.0b013e3182274803
Analgesia: Research Reports
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BACKGROUND: The sympathetic nervous system has important roles in mediating many neuropathic pain conditions. A thoracic sympathetic block (TSB) is a useful therapeutic procedure for neuropathic pain in the upper extremities and thorax. However, no studies have examined the factors related to an improved therapeutic effect of TSB. In this study, we evaluated the influence of potential prognostic factors for a better TSB effect and identified clinically important prognostic factors.

METHODS: Percutaneous TSB was performed in 51 patients, under fluoroscopic guidance. Data collected for each patient included age, gender, body mass index, diagnosis, pain intensity, and symptom duration. The adjusted odds ratios and 95% confidence intervals for each variable were calculated by logistic regression.

RESULTS: TSB was more effective in patients with symptom durations of ≤1 year compared with >1 year (P = 0.006; odds ratio, 8.037; 95% confidence interval, 1.808–35.729). Patient age, gender, body mass index, diagnosis, and intensity of pre-TSB pain were not associated with TSB effectiveness.

CONCLUSION: The results showed that an earlier TSB produced a better outcome for patients with chronic pain syndrome. Thus, early TSB should be performed in patients with chronic pain in the upper extremities.

Published ahead of print July 21, 2011

From the *Department of Anesthesiology and Pain Medicine, School of Medicine, Kyung Hee University, Seoul; Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam; and Samsung Seoul Hospital, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

The authors declare no conflicts of interest.

This report was previously presented, in part, at the World Society of Pain Clinicians Congress, Beijing, 2010.

Hyung Seok Yoo, MD, is currently affiliated with Bumin Hospital, Seoul, Korea. Chul Joong Lee, MD, is currently affiliated with ZEIN (zeropain) Pain Treatment Clinic, Seoul, Korea.

Reprints will not be available from the authors.

Address correspondence to Francis Sahngun Nahm, MD, Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, 166, Gumi-ro, Bundang-gu, Seongnam 463-707, Korea. Address e-mail to hiitsme@snubh.org.

Accepted May 13, 2011

Published ahead of print July 21, 2011

The sympathetic nervous system is implicated in many pain conditions, and blocking sympathetic ganglia with local anesthetics has beneficial effects in the treatment of sympathetically mediated pain.1 Although a stellate ganglion block by the anterior approach can be used to achieve a sympathetic block of the upper extremities, this procedure does not necessarily block the dermatomal thoracic sympathetic nerves.2 Kuntz reported that nerves from the second thoracic (T2) and third thoracic (T3) sympathetic ganglia connect to the brachial plexus in 20% of the population. As they bypass the stellate ganglion, this can result in the failure of a stellate ganglion block to relieve upper extremity pain.3,4 This finding led to the design of additional procedures to destroy or block the T2 and T3 sympathetic ganglia. A thoracic sympathetic block (TSB) has been a useful therapeutic procedure for pain treatment, including complex regional pain syndrome (CRPS), postherpetic neuralgia, phantom breast pain, and peripheral vascular disease of the upper extremities.58 TSB is performed via a percutaneous approach under fluoroscopic or computed tomographic guidance in many pain clinics. However, no studies have examined the factors related to a better TSB outcome. A detailed knowledge of prognostic and predictive factors would be useful for increasing the TSB treatment effect. The purpose of this study was to evaluate the influence of potential prognostic factors (i.e., age, gender, body mass index [BMI], disease, duration of disease, and pain intensity) on the effectiveness of TSB and to identify clinically significant prognostic factors.

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METHODS

Patients

This study was approved by the IRB of Seoul National University Bundang Hospital (IRB no. B-1008-110-106). After obtaining written, informed consent from the patients, we conducted this study on 51 consecutive patients who received TSB from February 2008 to August 2010. The inclusion criteria were as follows: (1) upper extremity pain due to CRPS, brachial plexopathy, postherpetic neuralgia, posttraumatic pain syndrome, or failed back surgery syndrome; (2) 6 weeks of standard treatment before undergoing TSB; and (3) average daily pain intensity of ≥4 points on a visual analog scale (VAS) (0 = no pain; 10 = worst pain imaginable) over the standard treatment period. Standard treatments included conservative treatment such as physical therapy; mono or combined pharmacologic therapy with nonsteroidal antiinflammatory drugs, tricyclic antidepressants, benzodiazepines, anticonvulsants, opioids, or a lidocaine patch; selective nerve block; and epidural analgesia. Exclusion criteria were as follows: (1) no increase in skin temperature ≥2°C on the palm after TSB, which was considered to indicate an unsuccessful TSB; and (2) medications or prescription dosages that were changed within 1 week before TSB or during the entire study period. No attempt was made to exclude smokers because this is a behavior that patients exhibit and the exact influence of smoking on the results is not known.

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TSB Procedure

Percutaneous TSB was performed in the operating room under fluoroscopic guidance using local anesthetics. The patient was placed in a prone position on a radiology table, and a 15-cm-high pillow was placed underneath the patient's anterior chest. Electrocardiogram, pulse oxymetry, and arterial blood pressure were monitored during each procedure, and peripheral IV access was obtained for administration of lactated Ringer solution. To evaluate the sympathetic block, the skin-surface temperature was monitored by small, adhesive thermocouple probes (Solar® 8000M; GE Healthcare, Milwaukee, WI) attached bilaterally to the patient's palms with transparent patches (Tegaderm®; 3M Healthcare, St. Paul, MN). A Quincke-type, 22-gauge, 12-cm spinal needle (Taechang Industrial Co., Kongju, Korea) was advanced in an oblique projection to the lateral margin of the T3 vertebra, using the tunnel vision technique under fluoroscopic guidance. When the proper needle position was achieved, 1 to 2 mL of contrast agent (Omnipaque®; Nycomed Ireland, Ltd., Cork, Ireland) was injected to confirm compartmental flow of the injectate and to identify any intravascular, intrathecal, epidural, or intrapleural spread. After proper needle position was confirmed, baseline skin temperature was measured and 5 mL of 0.25% levobupivacaine was injected. Skin temperature was measured at 5-minute intervals for 20 minutes after levobupivacaine injection. Sympathetic block was considered successful when the skin temperature of the affected side increased by ≥2°C.9

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Data Collection and Statistical Analysis

Approximately 2 weeks after TSB, patients were interviewed in person by the physician, and the degree of symptom change was measured on a 5-point Likert scale (0 = much aggravated; 1 = little aggravated; 2 = no change; 3 = little improved; and 4 = much improved). Patients with a 3 or 4 on the Likert scale were placed in the “effective TSB group,” and the others were placed in the “noneffective TSB group.” The following data were collected from each patient: age, gender, BMI, diagnosis, intensity of pre-TSB pain, and symptom duration. The adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated for each variable using logistic regression. The estimated logistic regression model was tested using Hosmer-Lemeshow goodness of fit. Symptom duration was chosen as the primary independent variable (X), and TSB effectiveness was the primary outcome (Y). The required sample size was calculated with G*power version 3.1.0 software, as reported previously,10,11 using the following conditions: (1) expected OR for the primary outcome = 5.0; (2) R2 (squared multiple correlation coefficient when the predictor of interest was regressed on the other predictors) = 0; (3) probability (Y = 1|X = 1) under the null hypothesis = 0.3; and (4) binomial distribution of X (≤l year vs >1 year) with a probability 0.5 α = 0.05 and β = 0.2 for a 1-tailed test. The calculation yielded 45 patients as a required sample size. PASW® version 17.0 software (SPSS, Chicago, IL) was used for statistical analysis. Results are expressed as means ± SD, and P values <0.05 indicated statistical significance.

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RESULTS

Fifty-one TSBs in 51 patients (12 women and 39 men) were performed successfully and without complications by 2 pain specialists with >3 years of experience. Patient characteristics are presented in Table 1, and changes in patient symptoms after TSB are presented in Table 2. The mean patient age was 46.10 ± 19.75 years (range, 20–82 years), and the mean duration of symptoms preceding TSB was 24.71 ± 49.12 months (range, 3–254 months). Most patients had received medication management with 2 to 5 classes of traditional analgesic and coanalgesic drugs used in chronic pain. The medications before TSBs are listed in Table 1. Patients' symptoms were as follows: tingling sensation (60.8%), sensitive to touch (54.9%), stabbing pain (41.2%), edema (31.4%), coldness (27.5%), throbbing pain (17.6%), burning pain (17.6%), and sharp pain (15.7%).

Table 1

Table 1

Table 2

Table 2

Among the 51 patients, 27 (52.9%) stated that the TSB was effective. TSB was more effective in patients with symptom durations of ≤1 year compared with >1 year (OR, 8.037; 95% CI, 1.808–35.729; P = 0.006). Among the 33 patients whose symptom duration was ≤1 year, 22 (66.7%) were in the TSB effective group, whereas only 5 of 18 patients (27.8%) whose symptom duration was >1 year received an effective TSB. Table 3 shows the adjusted ORs with 95% CIs of each variable for the effectiveness of TSB. Patient age, gender, BMI, diagnosis, and pre-TSB pain intensity were not associated with TSB effectiveness. The logistic regression model tested by Hosmer-Lemeshow goodness of fit showed the model's estimates fit the data at an acceptable level (P = 0.161).

Table 3

Table 3

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DISCUSSION

We found that an early TSB, within 1 year of symptom onset, was more effective for chronic upper extremity pain than treatment after 1 year. Several studies have reported the advantages of early sympathetic block; however, those studies were conducted only in patients with cancer pain or in animal models,1215 and not in patients with chronic noncancer pain. Our study is the first to report the advantages of early sympathetic block in patients with nonmalignant chronic pain disorders. The sympathetic nervous system has an important central role in chronic pain,1618 and the coupling between the sympathetic nervous system and the sensitized sensory nervous system is important for the development of sympathetically maintained pain.19

The modulation of pathologic pain through the sympathetic system involves noradrenalin (NA).20 Although peripheral NA has little effect on pain in normal tissues, it can aggravate pain and produce allodynia or hyperalgesia in pathologic conditions.21,22 The proposed mechanisms of this phenomenon are the sympathetic sprouting of nerve fibers,23,24 changes in noradrenergic receptor expression after nerve injury,25,26 and alteration in ionic channel properties of primary afferent nociceptors.27

Sympathetic nerve sprouting in the dorsal root ganglia (DRG) contributes to development and persistence of sympathetically maintained pain.28,29 Sprouting of sympathetic fibers and abnormal sympathetic sensory neuron interactions can also occur in the periphery.23 Systemic or locally administered anesthetics reduce sympathetic sprouting, mechanical pain behavior, spontaneous bursting activity, and cytokine and nerve growth factor production in the DRG.15,30,31 Therefore, a proposed mechanism for the effectiveness of early sympathetic block is the reduction of NA release and consequent prevention of sympathetic sprouting, followed by reduced sympathetic activity. Nerve injury evokes sympathetic fiber sprouting in the DRG, which activates wide dynamic range neurons in the dorsal horns. When sensitization persists, wide dynamic range neurons respond to large-diameter A-β mechanoreceptive afferents, which are activated by light touch such as brushing and produce allodynia.32,33 Alternatively, peripheral nerve axotomy induces hyperexcitation of DRG neurons via the sympathetic pathway, causing neuropathic pain characterized by hyperalgesia or allodynia.34 Thus, neuropathic pain requires continuous sensitization caused by either persistent afferent stimulation from injured nerves or functional changes in the DRG, as seen in sprouting of sympathetic fibers.

Several types of sympathetic blockade (e.g., stellate ganglion block and lumbar sympathetic block) have been studied for the treatment of neuropathic pain,5,35 but published information on TSB is limited. Furthermore, prognostic studies on the outcomes after TSB have not been performed. This study is the first report of prognostic factors for successful TSB.

Several points should be considered in our study. First, we used 12 months as the cutoff value for symptom duration. Before performing logistic regression analysis, we performed receiver operating characteristic curve analysis to determine the cutoff value of symptom duration as a predictor of “TSB effectiveness.” Receiver operating characteristic curve analysis showed 13 months as the best cutoff point with the highest accuracy (90.2%). However, there was only 1 patient whose symptom duration was 13 months in our study. Although we used 12 months as a criterion, the accuracy was similar (88.2%). Taking these findings into consideration, we chose 12 months as a cutoff value for ease of clinical application. Second, we measured the effectiveness of TSB as overall subjective satisfaction using a 5-point Likert scale, not a VAS. The pain characteristics of which the patients complained were very complicated. Because patients had difficulty describing detailed symptom improvement and recalling the degree of maximal pain reduction 2 weeks after TSB, we thought that the comprehensive effects of TSB (pain reduction, warmness, softness, and reduction of edema) would not be reflected by a simple VAS for pain. Several reports have indicated the usefulness of a Likert scale for measuring changes in function, and it is comparable to a VAS.36,37 Third, we evaluated the effectiveness of TSB over a short period of time; therefore, further study on the long-term effect of early TSB is required. Fourth, although only symptom duration was associated with the effectiveness of TSB in the present study, the relatively small sample size should be considered when interpreting the results. For example, CRPS type 2 showed an OR of 3.697 (95% CI, 0.169–80.773), which indicated a tendency for effective TSB; however, the 95% CI of the variable was wide because the sample size was relatively small. Additional studies with larger sample sizes are needed. Finally, the study population consisted of patients whose treatments were unsuccessful during a 6-week period. The results might have been different were the TSB performed without waiting for 6 weeks of conservative treatment.

Our study results highlight the importance of symptom duration as a distinct predictor of TSB treatment response in patients with chronic pain. Consequently, the clinical challenge is to limit symptom duration. Furthermore, the reported results support the hypothesis that there is a tendency toward progression of the illness, which may be associated with neurodegenerative changes in the sympathetic ganglion and impairment in the patient's responsiveness to treatment. In conclusion, we believe that performing TSB at an earlier time point can improve its therapeutic effect in patients with chronic upper extremity pain.

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DISCLOSURES

Name: Hyung Seok Yoo, MD.

Contribution: This author helped write the manuscript.

Attestation: Hyung Seok Yoo has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.

Name: Francis Sahngun Nahm, MD.

Contribution: This author helped design the study.

Attestation: Francis Sahngun Nahm has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Pyung Bok Lee, MD.

Contribution: This author helped conduct the study.

Attestation: Pyung Bok Lee has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Chul Joong Lee, MD.

Contribution: This author helped write the manuscript.

Attestation: Chul Joong Lee has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

This manuscript was handled by: Spencer S. Liu, MD.

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