Prediction of the Efficacy of Lumbar Sympathetic Block in Patients with Lower Extremity Complex Regional Pain Syndrome Type 1 Based on the Sympathetic Skin Response

Clinically, sympathetic activity is frequently observed to significantly enhance the degree of pain in CRPS patients, which is mediated by the coupling of sympathetic postganglionic C fibers with peripheral afferent sensory neurons to produce SMP [11, 12]. Sympathetic block is a typical treatment for CRPS pain and other symptoms, and its therapeutic effect varies greatly [13, 14]. It is difficult to determine which CRPS-1 features are required for effective sympathetic block. In this study, we employed a multivariate logistic regression model to explore predictors of successful symptom relief following LSB treatment. It was discovered that a baseline SSR amplitude of the affected extremity < 510 µV and disease duration < 12 months were predictors of successful LSB treatment.

Currently, the clinical diagnosis of CRPS mainly depends on the reported symptoms, presence of signs, and exclusion of alternative causes [15, 16], and there is still a lack of objective and quantitative diagnostic or prediction tests. Despite substantial autonomic dysfunction, CRPS-1 patients, unlike CRPS-2 patients, do not have impairments in motor and major sensory nerve fiber function [17]. As a consequence, nerve conduction velocity (NCV) is ineffective for diagnosis since it cannot detect thinly myelinated or unmyelinated small nerve fiber injury [18]. The SSR is the only autonomic test widely available on routine EMG equipment [19], which can substitute for the deficiencies of NCV by detecting the conduction function of sympathetic sudomotor fibers [18, 20, 21]. The SSR latency and amplitude can be changed in response to sympathetic hyperactivity of CRPS because it alters the sweat fibers, which in turn influences skin resistance [22]. Additionally, SSR has been shown to have good consistency with other autonomic function detection methods in diabetic neuropathy [23], uremic peripheral neuropathy [24], chemotherapy-induced peripheral neuropathy [25] and other diseases and can well evaluate the autonomic function impairment of these diseases.

There are very few articles investigating the role of SSR in CRPS diagnosis and treatment. In one study [26], CRPS patients showed prolonged latency of SSR. In another study [27], it was found that the mean amplitude was higher on the affected side, while the mean latency was shortened. However, after sympathetic block, amplitude was reduced, and latency was prolonged. The two studies had contradictory results, most likely because they were all restricted by a small number of patients. Lee et al. [28]. compared the results of sympathetic blocks to those of 263 people who had completed combined autonomic nervous system (ANS) testing to identify CRPS. Although the incidences of abnormal SSR tests were not substantial, they were considerably higher in the CRPS group. However, this study did not conduct quantitative stratification of SSR parameters and instead filtered out SSR-positive patients. As the pathogenic mechanism of the sympathetic nerve in CRPS has become more apparent in recent years [29], the application of sympathetic block treatment has increased again. As a result, choosing the most appropriate patients for individualized treatment is essential. According to our findings, following LSB to alleviate pain, the mean SSR amplitude increased, and the mean SSR latency shortened on the affected side (Fig. 3). These findings support LSB's effective treatment of pain symptoms in CRPS patients and clarify the range of changes in SSR parameters.

The current study used a cohort of unilateral CRPS-1 lower extremity patients from our institution, regardless of disease severity. The value of SSR has been widely reported for several autonomic nerve disorders [23, 30], but the treatment of CRPS, particularly the prediction of successful symptom relief, has received relatively less attention. In our research, 98 CRPS-1 patients had two LSB treatments in 1 month. A total of 43.9% of the patients (43/98) experienced successful symptom relief, whereas 56.1% of the patients (55/98) had unsuccessful symptom relief. This result is better than that of one prior study [31], which found that just 31% of CRPS-1 patients responded well to sympathetic block. In contrast to our study, the subjects involved upper and lower extremities. Another study [32] discovered that 61% of CRPS patients effectively reacted to LSB, making it the most effective study of LSB in recent literature and yielding a higher rate than our findings. It is worth noting that there was a significant difference in the SSR amplitude of the affected limbs between the two groups in our study but not in the SSR latency. It is generally believed that latency is a relatively stable parameter that does not change markedly with different stimuli, and it reflects the conduction duration of the nerve impulse that generates perspiration throughout the reflex arc [33]. However, the amplitude is a reliable response of the excitability of sympathetic postganglionic fibers and sweat glands, which is more able to reflect peripheral sympathetic nerve activity [34]. It is also worth mentioning that, according to the Budapest criteria, vasomotor and sweating/edema, which are CRPS symptoms, were more prevalent in the LSB (+) group. It could be that these two types of symptoms are most closely linked to sympathetic activity [35].

The reasons for the clinical positive response to LSB are multifaceted. Our results showed a significant difference in the change in SSR amplitude between the LSB (−) and LSB (+) groups before and after treatment. The effectiveness of LSB could potentially be predicted by changes in SSR amplitude (Fig. 4). Therefore, we analyzed age, BMI, sex, disease duration, baseline NRS, baseline SSR latency and amplitude. In accordance with previous research [36] on predictors, our results show that disease duration appears to be a factor determining the success of LSB, with patients having less than 12 months exhibiting a fourfold higher efficiency than patients with a longer duration. This indicates that CRPS with a duration ≥ 12 months is a poor prognostic factor for successful LSB treatment. Patients with CRPS may develop central sensitization, which can explain why sympathetic block is less effective over time [37]. SSR is thought to be triggered by synchronized sweat gland activity. The afferent part of the SSR is composed of large myelinated peripheral sensory fibers, whereas the efferent part is composed of sympathetic postganglionic unmyelinated C fibers that terminate in sweat glands. SSR is considered to be altered in CRPS due to increased sympathetic activity (4). In our results, an SSR amplitude < 510 µV was a good prognostic factor for successful LSB treatment.

This study has a number of limitations. First, this study lacked healthy controls and relied entirely on the healthy lower limbs of CRPS patients for control, which is known as contralateral control. As normal SSR parameter values have not yet formed a unified standard, our judgment of values in this study is based on neurologists' interpretation. Second, the LSB's efficacy was judged by short-term pain alleviation with no long-term follow-up. Although we could not find a long-term effect of LSB in our investigation, we managed to record the NRS following treatment 1 week after two LSB sessions. Third, we did not examine inflammatory cytokines or pain-related mediators to determine whether there were any changes in biomarkers. Finally, as we conducted a single-center study, it is possible hard to generalize our findings.

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