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).
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,12–15 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,16–18 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.
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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