Transient immune activation without loss of intraepidermal innervation and associated Schwann cells in patients with complex regional pain syndrome.

BACKGROUND: Complex regional pain syndrome (CRPS) develops after injury and is characterized by disproportionate pain, oedema, and functional loss. CRPS has clinical signs of neuropathy as well as neurogenic inflammation. Here, we asked whether skin biopsies could be used to differentiate the contribution of these two systems to ultimately guide therapy. To this end, the cutaneous sensory system including nerve fibres and the recently described nociceptive Schwann cells as well as the cutaneous immune system were analysed. METHODS: We systematically deep-phenotyped CRPS patients and immunolabelled glabrous skin biopsies from the affected ipsilateral and non-affected contralateral finger of 19 acute (< 12 months) and 6 chronic (> 12 months after trauma) CRPS patients as well as 25 sex- and age-matched healthy controls (HC). Murine foot pads harvested one week after sham or chronic constriction injury were immunolabelled to assess intraepidermal Schwann cells. RESULTS: Intraepidermal Schwann cells were detected in human skin of the finger-but their density was much lower compared to mice. Acute and chronic CRPS patients suffered from moderate to severe CRPS symptoms and corresponding pain. Most patients had CRPS type I in the warm category. Their cutaneous neuroglial complex was completely unaffected despite sensory plus signs, e.g. allodynia and hyperalgesia. Cutaneous innate sentinel immune cells, e.g. mast cells and Langerhans cells, infiltrated or proliferated ipsilaterally independently of each other-but only in acute CRPS. No additional adaptive immune cells, e.g. T cells and plasma cells, infiltrated the skin. CONCLUSIONS: Diagnostic skin punch biopsies could be used to diagnose individual pathophysiology in a very heterogenous disease like acute CRPS to guide tailored treatment in the future. Since numbers of inflammatory cells and pain did not necessarily correlate, more in-depth analysis of individual patients is necessary.

Inflammation induces α1-adrenoceptor expression in peripheral blood mononuclear cells of patients with complex regional pain syndrome.

Persistent regional and systemic inflammation may promote pain and hyperalgesia in complex regional pain syndrome (CRPS). In this study, we investigated whether stimulation of α1-adrenoceptors (α1-AR) on peripheral blood mononuclear cells (PBMC) might contribute to this inflammatory state. PBMC were isolated from venous blood collected from 21 CRPS patients and 21 sex and age-matched controls. Lipopolysaccharide (LPS), a bacterial toxin, was administered to cultured PBMC for 24 h to trigger inflammation. Exposure to LPS resulted in heightened gene expression of α1-AR subtype B (α1B-AR) in PBMC of CRPS patients relative to controls. Interleukin (IL)-1ß and IL-6 levels did not change when the α1-AR agonist phenylephrine was administered to naïve PBMC. However, α1-AR stimulation following LPS treatment increased IL-6 mRNA and protein levels in PBMC of patients and controls. To investigate the possible consequence of heightened IL-6 levels on immunoglobulin G antibody production, PBMC were stimulated with CD40 ligand and IL-21 to generate plasmablasts (B cells that secrete antibodies). This response was similar in patients and controls. Adding IL-6 to the cell culture medium increased plasmablast differentiation in controls and antibody production both in patients and controls. These findings suggest that the inflammatory cascade associated with elevated levels of IL-6 may generate α1B-AR expression in CRPS PBMC. A reciprocal interaction between heightened α1-AR expression in PBMC and IL-6 secretion may contribute to systemic inflammation and antibody production in CRPS.

Differential effects of everyday-life social support on chronic pain.

BACKGROUND: Social support is a multidimensional construct encompassing emotional support as well as pain-focused care and attention, also known as solicitous support. One the one hand, social support is widely believed to positively influence pain symptoms, their intensity, and the ability to cope and influence pain. On the other hand, social support can be negative if it conflicts with the patient's needs or even causes discomfort. How different types of social support influence pain is not very well understood especially because most of the present research originates from laboratory studies, raising uncertainties about its generalizability to the everyday life of individuals with chronic pain. METHODS: Here, we tested the effects of emotional, solicitous, and negative social support on pain intensity cross-sectionally in everyday life. We collected data from 20 patients with acute complex regional pain syndrome using a smartphone-based Ecological Momentary Assessment with up to 30 survey prompts over a period of five consecutive days. RESULTS: Our results showed that solicitous social support decreased pain, in particular in male patients. Emotional support was beneficial on pain in women but not in men. CONCLUSIONS: Taken together, these findings highlight the differential effects of social support in every-day life on chronic pain.

Erythromelalgia. Part II: Differential diagnoses and management.

The management of erythromelalgia is challenging and requires multidisciplinary effort. Patient education is crucial as unsafe self-administered cooling techniques can lead to significant morbidity, including acral necrosis, infection, and amputation. The goal of management is pain control, reduction of flare frequency, and prevention of complications. This text is focused on the management of erythromelalgia and several other incompletely understood and under-recognized neurovascular disorders such as red scrotum syndrome, red ear syndrome, facial flushing, and complex regional pain syndrome.

Erythromelalgia. Part I: Pathogenesis, clinical features, evaluation, and complications.

Erythromelalgia is a rare pain disorder that is underrecognized and difficult-to-treat. It is characterized by episodes of extremity erythema and pain that can be disabling; it may be genetic, related to an underlying systemic disease, or idiopathic. Considering the prominent cutaneous features characteristic of the condition, dermatologists can play an important role in early recognition and limitation of morbidity. The first article in this 2-part continuing medical education series reviews the epidemiology, pathogenesis, clinical manifestations, evaluation, and complications.

Effect of an interdisciplinary inpatient program for patients with complex regional pain syndrome in reducing disease activity-a single-center prospective cohort study.

OBJECTIVE: The aim of this study was to evaluate the benefit of inpatient treatment in reducing disease activity in patients with complex regional pain syndrome (CRPS) who have exhausted outpatient options. Furthermore, the study sought to identify patient-related outcome variables that predict a reduction in disease activity. METHODS: The primary outcome was disease severity (CRPS Severity Score, range 0-16 points). Secondary outcomes included depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and the ability to participate in social roles and activities, all of which were assessed using the PROMIS-29. Furthermore, pain catastrophizing, neuropathic pain, quality of life, pain self-efficacy, medication intake, and the patient's global impression of change were examined in accordance with current international agreed recommendations, assessed at discharge, 3-month, and 6-month post-discharge. Mixed-effects models were conducted to identify baseline variables associated with CRPS severity. RESULTS: Twenty-five patients completed the program (mean age 49.28 [SD 11.23] years, 92% females, mean symptom duration 8.5 [SD 6.5] months). Results showed a significant reduction between baseline and discharge of disease activity (CSS -2.36, P < .0001), pain (PROMIS-29 pain -0.88, P = .005), and emotional function (PROMIS-29 depression -5.05, P < .001; fatigue -4.63, P = .002). Moderate evidence for a reduction between baseline and discharge could be observed for pain interference (+2.27, P = .05), social participation (PROMIS-29 + 1.93, P = .05), anxiety (PROMIS-29 -3.32, P = .02) and physical function (PROMIS-29 + 1.3, P = .03). On discharge, 92% of patients (23 of 25) reported improvement in their overall condition. In the follow-up period, medication intake could be reduced after 3 (MQS -8.22, P = .002) and 6 months (MQS -8.69, P = .001), and there was further improvement in social participation after 3 months (PROMIS-29 + 1.72, 0.03) and sleep after 6 months (PROMIS-29 + 2.38, 0.008). In the mixed models, it was demonstrated that patients experiencing less pain at baseline also exhibited lower disease activity. CONCLUSION: The results of this study confirm that inpatient interdisciplinary treatment of CRPS patients improves disease activity, pain, physical function, emotional function, and social participation. Most improvements were maintained for up to 6 months after discharge. The majority of patients reported that their overall condition had improved during the study period.

Evaluation of thoracic sympathetic ganglion block as a predictor for response to ketamine infusion therapy and spinal cord stimulation in patients with chronic upper extremity pain.

OBJECTIVE: To investigate the predictive value of thoracic sympathetic ganglion block (TSGB) in response to ketamine infusion therapy (KIT) and spinal-cord stimulation (SCS) in patients with chronic upper-extremity pain including complex regional pain syndrome (CRPS). DESIGN: Retrospective. SETTING: Tertiary hospital single-center. SUBJECTS: Patients who underwent TSGB receiving KIT or SCS within a 3-year window. METHODS: Positive TSGB outcomes were defined as ≥2 0-10 Numerical Rating Scale (NRS) score reduction at 2 weeks post-procedure. Positive KIT and SCS outcomes were determined by ≥2 NRS score reduction at 2-4 weeks post-KIT and ≥4 NRS score reduction at 2-4 weeks post-SCS implantation, respectively. RESULTS: Among 207 patients who underwent TSGB, 38 received KIT and 34 underwent SCS implantation within 3 years post-TSGB; 33 patients receiving KIT and 32 patients receiving SCS were included. Among 33 patients who received KIT, 60.6% (n = 20) reported a ≥ 2 0-10 NRS pain-score reduction. Positive response to TSGB occurred in 70.0% (n = 14) KIT responders, significantly higher than that in 30.8% (n = 4) KIT non-responders. Multivariable analysis revealed a positive association between positive responses to TSGB and KIT (OR 7.004, 95% CI 1.26-39.02). Among 32 patients who underwent SCS implantation, 68.8% (n = 22) experienced short-term effectiveness. Positive response to TSGB was significantly higher in SCS responders (45.5%, n = 10) than in non-responders (0.0%). However, there were no associations between pain reduction post-TSGB and that post-KIT or post-SCS. CONCLUSIONS: A positive response to TSGB is a potential predictor for positive KIT and SCS outcomes among patients with chronic upper-extremity pain, including CRPS.

The Effectiveness of Hyperbaric Oxygen Treatment in Patients with Complex Regional Pain Syndrome: A Retrospective Case series.

Background: Complex regional pain syndrome (CRPS) presents as persistent regional pain, both spontaneous and triggered. The demand persists for innovative treatments that patients can endure with minimal adverse effects. Hyperbaric oxygen therapy (HBOT) emerges as a possible intervention in this regard. Methods: The main objective of this work is to retrospectively analyse a case series of patients diagnosed with CRPS treated in the Centre of Hyperbaric Medicine Ostrava over two years (period 2018-2019). The HBOT was applied at 2.0-2.4 absolute atmosphere (ATA) once a day. Results: A total of 83 patients with CRPS were treated with HBOT. 98% of cases reported pain, 92% reported limitation of movement of the affected limb, 87% had swelling of the limb, 41% had lividity and 70% had sensory problems. The mean number of HBOT exposures was 22.0 ± 7.1. At the end of HBOT treatment, 86% of cases had symptoms relief. The mean VAS value of pain at rest before the start of HBOT was 3.2±3.0, after treatment it was 1.6±1.9 (p<0.001). In a pain at activity it was 6.1±2.4 and 3.7±2.4 (p<0.001), respectively, at the end of HBOT. The value of the functional assessment of the limb was 7.0±2.0 and 4.3±2.4 (p<0.001), respectively, at the end of treatment. 79 cases were included in the end-of-treatment assessment. 23 cases (29%) were evaluated as large clinically significant response, 48 cases (61%) were evaluated as partial response with minimally important difference. The results showed larger clinical HBOT effect in cases of disease duration up to 3 and 6 months (p=0.029). Conclusions: The majority of patients improved pain and functional state of the affected limb. Our data also suggests the sooner after diagnosis of CRPS is HBOT started, the treatment has larger clinical effect. There was no serious HBOT-related complication or injury.

Complex regional pain syndrome: diagnostic challenges and favorable response to prednisolone.

Complex regional pain syndrome (CRPS), characterized by severe and disproportionate pain, is a rare and debilitating condition. Due to its rarity, evidence-based treatment guidelines remain limited, creating a challenge for clinicians. We present the case of a 20-year-old female with CRPS type 1 of the right hand. Her pain, initially triggered by a minor trauma, had persisted for three months. The patient demonstrated severe pain, swelling, hyperesthesia, and restricted range of motion. Despite multiple hospital visits, her symptoms did not improve until she was diagnosed with CRPS and treated with oral prednisolone. A dosage of 40 mg daily led to a dramatic response within 10 days. Our report emphasizes the importance of recognizing CRPS and highlights the potential of prednisolone as a treatment option, particularly in resource-limited settings, where more specialized interventions may be unavailable. Further research is essential to establish a stronger evidence base for the use of steroids in CRPS management.

Dorsal Root Ganglion Size in Patients With Complex Regional Pain Syndrome of the Lower Extremity: A Retrospective Pilot Study.

OBJECTIVE: Complex regional pain syndrome (CRPS) is a debilitating chronic condition characterized by severe, nociplastic pain along with various other symptoms. Neuromodulation, particularly electrical stimulation of the dorsal root ganglion (DRG), has emerged as a promising intervention for patients with CRPS unresponsive to conventional treatments. However, little is known about the anatomical characteristics of DRGs in patients with CRPS. This study aimed to assess DRG size in patients with CRPS compared with healthy controls. MATERIALS AND METHODS: A retrospective pilot study was conducted in 12 patients with unilateral lower extremity CRPS who have a history of lumbar magnetic resonance imaging, and evaluated DRG sizes bilaterally. Patients were age-, race-, and sex-matched to patients in the control group who were asymptomatic at matched spinal level. DRG sizes were evaluated by a neuroradiologist. Statistical analyses including paired t-tests were performed to compare the difference in DRG size in contralateral sides in patients with CRPS and their matched controls. RESULTS: Patients with CRPS exhibited a statistically significant reduction in DRG size on the affected side compared with the unaffected side (4.4 mm-4.8 mm, respectively). This difference was significant when compared with the difference observed in healthy controls (4.9 mm-5.0 mm, respectively). In addition, the mean DRG size difference between the affected and unaffected side showed a greater difference in DRG size in patients with CRPS (0.6 mm difference) than in control patients (0.2 mm difference). CONCLUSIONS: The findings suggest that CRPS is associated with a smaller DRG size in affected dermatomes, potentially indicating neuronal atrophy. Importantly, the study offers insights for DRG stimulation therapy especially among concerns for DRG compression after placement. This pilot study reveals a significant size difference in DRGs between affected and unaffected sides in patients with CRPS compared with controls, highlighting potential implications for treating CRPS. Further research is warranted to validate these findings and explore implications for clinical practice, including optimized neuromodulation strategies.

Neural Correlates of Pain-Autonomic Coupling in Patients With Complex Regional Pain Syndrome Treated by Repetitive Transcranial Magnetic Stimulation of the Motor Cortex.

OBJECTIVES: Complex regional pain syndrome (CRPS) is a chronic pain condition involving autonomic dysregulation. In this study, we report the results of an ancillary study to a larger clinical trial investigating the treatment of CRPS by neuromodulation. This ancillary study, based on functional magnetic resonance imaging (fMRI), evaluated the neural correlates of pain in patients with CRPS in relation to the sympathetic nervous system and for its potential relief after repetitive transcranial magnetic stimulation of the motor cortex. MATERIALS AND METHODS: Eleven patients with CRPS at one limb (six women, five men, aged 52.0 ± 9.6 years) were assessed before and one month after the end of a five-month repetitive transcranial magnetic stimulation (rTMS) therapy targeting the motor cortex contralateral to the painful limb, by means of electrochemical skin conductance (ESC) measurement, daily pain intensity scores on a visual numerical scale (VNS), and fMRI with motor tasks (alternation of finger movements and rest). The fMRI scans were analyzed voxelwise using ESC and VNS pain score as regressors to derive their neural correlates. The criterion of response to rTMS therapy was defined as ≥30% reduction in VNS pain score one month after treatment compared with baseline. RESULTS: At baseline, ESC values were reduced in the affected limb vs the nonaffected limb. There was a covariance of VNS with brain activation in a small region of the primary somatosensory cortex (S1) contralateral to the painful side on fMRI investigation. After rTMS therapy on motor cortex related to the painful limb, the VNS pain scores significantly decreased by 22% on average. The criterion of response was met in six of 11 patients (55%). In these responders, at one month after treatment, ESC value increased and returned to normal in the CRPS-affected limb, and overall, the increase in ESC correlated with the decrease in VNS after motor cortex rTMS therapy. At one month after treatment, there also was a covariance of both variables (ESC and VNS) with fMRI activation of the S1 region previously mentioned. The fMRI activation of other brain regions (middle frontal gyrus and temporo-parietal junction) showed correlation with ESC values before and after treatment. Finally, we found a positive correlation at one month after treatment (not at baseline) between VNS pain score and fMRI activation in the temporo-parietal junction contralateral to painful side. CONCLUSIONS: This study first shows a functional pain-autonomic coupling in patients with CRPS, which could involve a specific S1 region. However, the modulation of sympathetic sudomotor activities expressed by ESC changes was rather correlated with functional changes in other brain regions. Finally, the pain relief observed at one month after rTMS treatment was associated with a reduced activation of the temporo-parietal junction on the side in which rTMS was performed. These findings open perspectives to define new targets or biomarkers for using rTMS to treat CRPS-associated pain. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02817880.

Improvement in Health-Related Quality of Life With Spinal Cord Stimulation in Complex Regional Pain Syndrome: A Single-Center, Retrospective Study.

BACKGROUND: Complex regional pain syndrome (CRPS) can profoundly affect many aspects of everyday life. Spinal cord stimulation (SCS) is a potential therapeutic option. This retrospective, single-site evaluation explored health-related quality of life (HRQoL) in individuals with CRPS treated with SCS in our Pain Service. MATERIALS AND METHODS: All patients aged ≥18 years with fully implanted SCS for CRPS between June 2013 and January 2023 were identified from hospital records. The following data were collected: sex, age, chronic pain diagnosis, CRPS type (I or II), location of CRPS (upper or lower limb), years of CRPS before first SCS implant, SCS system, preimplant and follow-up scores for HRQoL (euroqol 5 dimensions 3 levels [EQ-5D-3L] index score), average pain, worst pain and the influence of pain on aspects of everyday life (all numerical rating scale [NRS]), patient and clinician global impression of change at follow-up, and the occurrence and reasons for revisions and explants. An intention-to-treat approach was used and data statistically analyzed. RESULTS: The final cohort comprised 83 patients (46 women), with a median (minimum, maximum) follow-up duration of 29 months (seven, 72). There were statistically and clinically significant improvements in HRQoL, despite relatively low pain response rates. The pain response rate was 34% (reduction of ≥30% in average pain NRS); the pain remission rate was 13% (average pain score ≤3 NRS), and all patients had preimplant EQ-5D-3L index values below the population norm of 0.82. However, 60% of patients reported EQ-5D-3L index scores greater than the published minimally important difference of 0.074, and scores were better at follow-up than at preimplant (p < 0.001); 44% of patients and 41% of clinicians reported improved symptoms at the most recent follow-up. Explants occurred in eight of 83 patients (10%). CONCLUSIONS: Patients had meaningful improvements in HRQoL, which is a key outcome in ascertaining the overall outcome of SCS in CRPS. Randomized controlled clinical trials should build on the findings to improve understanding of the benefits and risks of treating CRPS with SCS.

Prevalence and predisposing factors of post-stroke complex regional pain syndrome: Retrospective case-control study.

INTRODUCTION: Poststroke complex regional pain syndrome (CRPS) is an important complication in stroke survivors. The identification of factors associated with post-stroke CRPS is important for preventive measures and early diagnosis. METHODS: A total of 141 first-ever stroke survivors in the subacute stage were retrospectively analyzed. Demographic data, diagnosis time, duration of hospitalization, location of brain lesion, etiology, comorbidities, and blood test findings were investigated. Clinical data included Medical Research Council (MRC) grade, Fugl-Meyer assessment (FMA), National Institute for Health Stroke Scale (NIHSS), Berg Balance Scale (BBS). RESULTS: Among 141 patients with subacute stroke, 22 were diagnosed with CRPS, with a prevalence of 15.6 %. The mean time to diagnosis was 38.6 (±16.5) days. The prevalence according to the degree of paralysis was 33.3 % in MRC grades 0 and 1, 8.6 % in grade 2, and 0 % in grade 3 or higher. The incidence rates within 1 month after stroke were 1.42 % and 22.47 % between 1 and 3 months after stroke, respectively. The independent risk factors for CRPS were hospitalization duration and FMA, NIHSS, and BBS scores. The sensitivity and specificity of the NIHSS score for predicting post-stroke CRPS were 86.4 % and 59.7 %, respectively, with an optimal cutoff value of 7.5. CONCLUSIONS: CRPS of the affected upper limb in stroke patients is associated with stroke severity, including paralysis, and the incidence increases over time during the subacute phase. Additionally, having sufficient strength to move through a full range of motion against gravity had a protective effect against CRPS.

[Prospective, multicenter study of the outcome of complex regional pain syndrome after 12 months]. / Prospektive, multizentrische Untersuchung des Outcomes nach 12 Monaten beim komplexen regionalen Schmerzsyndrom.

BACKGROUND AND OBJECTIVES: Complex regional pain syndrome (CRPS) can lead to severe pain and limited functionality in the long term. Guidelines should help to optimize treatment procedures. It should be investigated which outcome is achieved after 1 year with guideline-based therapy. MATERIALS AND METHODS: In a prospective multicenter study, 40 patients with newly diagnosed CRPS were examined to determine how their pain and functional limitations changed within 1 year. In addition, it was investigated whether the time of diagnosis and invasive measures influence these outcome parameters. RESULTS: All patients received physiotherapy and/or ergotherapy, treatment with glucocorticoids and/or bisphosphonates 29 (72.5%); various invasive measures were carried out in 13 (32.5%). After 1 year, both pain and functionality were significantly improved; two-thirds reported a tolerable average pain intensity. Severe functional impairment according to von Korff disability points was found after 1 year in 9 (22.5%), and a moderate or severe impairment according to medical evaluation in 6 (15%) and 3 (7.5%) patients, respectively. Earlier diagnosis and corresponding earlier start of treatment correlated with better outcome in terms of pain and functionality according to von Korff, but not according to medical evaluation. The influence of invasive procedures on the outcome parameters tended to be low. CONCLUSION: Guideline-based treatment led to a good outcome in terms of pain and functionality in the majority of patients. Early diagnosis correlated with better outcome, so suspected cases should be referred quickly to a medical facility with appropriate expertise.

The efficacy of oral corticoids in treating complex regional pain syndrome: A retrospective cohort study.

OBJECTIVES: There is growing evidence supporting the role of inflammatory mechanisms in complex regional pain syndrome (CRPS). Corticoids, as most effective anti-inflammatory drugs, are widely used in treating inflammation. The aim of this study was to retrospectively assess the efficacy of oral corticoid treatment in CRPS patients. METHODS: Patients treated at the center of pain medicine in the Erasmus University Medical Centre between January 2015 and January 2020 were approached to partake in this study. Medical records were screened for age, gender, medical history, duration of CRPS, and CRPS severity score. Also, treatment effect, dose and duration, pain scores (NRS), and side effects were extracted from medical records. In addition, global perceived effect was completed in patients treated with corticoids. RESULTS: Between January 2015 and January 2020, twenty-nine CRPS patients received corticoids and met the inclusion criteria. One extreme outlier was excluded and treatment effect was unknown for one patient. Average daily dose was 28.9 mg (range 10-30 mg) and the mean treatment duration was 10.5 days (7-21 days). Fourteen patients (51.9%) responded positively to treatment and thirteen (48.1%) did not respond. Side effects were reported in five patients (17.9%). CONCLUSIONS: Corticoid treatment was effective in more than half of the patients. With only mild side effects reported the treatment also appears to be relatively safe. Further research is needed to investigate the efficacy of corticoids in treating (early) CRPS, preferably in an intervention study.

10 kHz stimulation as rescue therapy for spinal cord stimulation trial failure or loss of efficacy: A retrospective study.

INTRODUCTION: Spinal cord stimulation (SCS) is currently used for the management of pain of different origin, and since its inception, many waveforms have been developed. Some patients experience no pain relief already during SCS trial, while other patients go through a loss of efficacy due to habituation after a variable period of satisfying pain control. Our retrospective study represents the first report exploring the potential role of 10 kHz stimulation as rescue therapy for patients who did not benefit not only from conventional stimulation but even from other waveforms during SCS trial or follow-up. METHODS: This study was conducted in Germany; we retrospectively enrolled patients with no pain relief during SCS trial or with loss of efficacy of other waveforms over time; and we recorded visual analogic scale (VAS), Oswestry Disability Index (ODI), and daily opioid consumption expressed as morphine milligram equivalents (MME), right before and 12 months after the switching to 10 kHz simulation. RESULTS: The rate of successful switching to 10 kHz stimulation was comparable in patients enrolled during the SCS trial and during the follow-up (43% vs. 40%, respectively); notably, the highest rate of failed rescue was recorded in case of persistent spinal pain syndrome (PSPS) II. Patients who responded to the switching showed a significant improvement in VAS and ODI after 12 months of treatment compared to baseline (3.6 ± 1.0 vs. 8.2 ± 0.9, p < 0.00001 and 34.0 ± 7.8 vs. 64.3 ± 8.7, p < 0.0001, respectively), whereas there was no reduction in the consumption of opioids in terms of MME (3 (0-16) vs. 5 (0-8.75), p = 0.1003). CONCLUSIONS: Rescue therapy with 10 kHz stimulation could be an important strategy to avoid SCS explant in both patients non-responsive during trial or experiencing a loss of efficacy during the years with other waveforms.

Effectiveness of motor imagery in complex regional pain syndrome: A systematic review with meta-analysis.

OBJECTIVE: The purpose of this study was to determine the effects of motor imagery (MI) on pain intensity and disability in individuals with complex regional pain syndrome (CRPS). METHODS: A systematic search was conducted in various electronic databases to identify all relevant studies: PubMed, CINAHL, WOS, PEDro, CENTRAL, and Scopus. Randomized controlled trials assessing the effects of MI in individuals with CRPS were included. The risk of bias was assessed with the Cochrane Risk of Bias tool, the methodological quality was evaluated using PEDro scale, and the level of evidence was reported according to the GRADE. Between-groups standardized mean differences (SMD) were calculated. RESULTS: Six studies were included. The meta-analysis found moderate-quality evidence that MI improves pain intensity and related disability as immediate (pain: SMD -1.07, 95% CI: -1.53 to -0.60; disability: SMD 1.05, 95% CI: 0.59 to 1.51), short-term (pain: SMD -1.28, 95% CI: -2.14 to -0.42; disability: SMD 1.37; 95% CI: 0.16 to 2.58), and long-term effects (pain: SMD -1.18; 95% CI: -1.89 to -0.46; disability: SMD 1.18; 95% CI: 0.46 to 1.89), as compared with a comparison group. The risk of bias of the trials was relatively low, but the imprecision of the results downgraded the level of evidence. CONCLUSIONS: Moderate-quality evidence suggests a positive effect of MI for improving pain intensity and disability immediately after and at short-term in individuals with CRPS.

10. Complex regional pain syndrome.

INTRODUCTION: Complex regional pain syndrome (CRPS) is a clinical disorder that can develop following surgery or trauma. Based on the most prominent underlying pathophysiological mechanisms, CRPS can be classified into different subtypes, namely inflammatory, nociplastic/neuropathic, vasomotor, and motor. Depending on the subtype, personalized treatment can be applied. If conservative treatments are insufficient or ineffective, more invasive treatments may be recommended. This article provides an overview of the most recent insights into CRPS and discusses the most common invasive treatments. METHODS: The literature regarding interventional treatments for CRPS has been systematically reviewed and summarized. RESULTS: Bisphosphonates are effective in treating the inflammatory subtype, while ketamine can provide pain relief for the nociplastic/neuropathic subtype. Sympathetic blocks are effective in addressing vasomotor disturbances. For patients with refractory symptoms, neurostimulation is a viable option due to its multimechanistic properties for all subtypes. End-of-line motor disturbances may benefit from intrathecal baclofen. CONCLUSIONS: CRPS is a debilitating condition with an unpredictable course. The effectiveness of treatment varies from patient to patient. When conservative approaches prove insufficient, gradual progression to invasive treatments based on the underlying subtype is recommended.

Stellate ganglion block beyond chronic pain: A literature review on its application in painful and non-painful conditions.

Cervical sympathetic or stellate ganglion blocks (SGBs) have been commonly used in the treatment of painful conditions like complex regional pain syndrome (CRPS). However, there is literature to suggest its utility in managing non-painful conditions as well. The focus of this literature review is to provide an overview of indications for SGB for painful and non-painful conditions. We identified published journal articles in the past 25 years from Embase and PubMed databases with the keywords "cervical sympathetic block, stellate ganglion blocks, cervical sympathetic chain, and cervical sympathetic trunk". A total of 1556 articles were obtained from a literature search among which 311 articles were reviewed. Among painful conditions, there is a lack of evidence in favor of or against the use of SGB for CRPS despite its common use. SGB can provide postoperative analgesia in selective surgeries and can be effective in temporary pain control of refractory angina and the acute phase of herpes zoster infection. Among non-painful conditions, SGB may have beneficial effects on the management of post-traumatic stress disorder (PTSD), refractory ventricular arrhythmias, hot flashes in postmenopausal women, and breast cancer-related lymphedema. Additionally, there have been various case reports illustrating the benefits of SGB in the management of cerebral vasospasm, upper limb erythromelalgia, thalamic and central post-stroke pain, palmar hyperhidrosis, orofacial pain, etc. In our review of literature, we found that SGB can be useful in the management of various non-painful conditions beyond the well-known treatment for CRPS, although further studies are required to prove its efficacy.

Somatotopic disruption of the functional connectivity of the primary sensorimotor cortex in complex regional pain syndrome type 1.

In complex regional pain syndrome (CRPS), the representation area of the affected limb in the primary sensorimotor cortex (SM1) reacts abnormally during sensory stimulation and motor actions. We recorded 3T functional magnetic resonance imaging resting-state data from 17 upper-limb CRPS type 1 patients and 19 healthy control subjects to identify alterations of patients' SM1 function during spontaneous pain and to find out how the spatial distribution of these alterations were related to peripheral symptoms. Seed-based correlations and independent component analyses indicated that patients' upper-limb SM1 representation areas display (i) reduced interhemispheric connectivity, associated with the combined effect of intensity and spatial extent of limb pain, (ii) increased connectivity with the right anterior insula that positively correlated with the duration of CRPS, (iii) increased connectivity with periaqueductal gray matter, and (iv) disengagement from the other parts of the SM1 network. These findings, now reported for the first time in CRPS, parallel the alterations found in patients suffering from other chronic pain conditions or from limb denervation; they also agree with findings in healthy persons who are exposed to experimental pain or have used their limbs asymmetrically. Our results suggest that CRPS is associated with a sustained and somatotopically specific alteration of SM1 function, that has correspondence to the spatial distribution of the peripheral manifestations and to the duration of the syndrome.