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Brain imaging studies in complex regional pain syndrome (CRPS) have found mixed evidence for functional and structural changes in CRPS. In this cross-sectional study, we evaluated two patient cohorts from different centers and examined functional connectivity (rsFC) in 51 CRPS patients and 50 matched controls. rsFC was compared in predefined ROI pairs, but also in non-hypothesis driven analyses. Resting state (rs)fMRI changes in default mode network (DMN) and the degree rank order disruption index (k D ) were additionally evaluated. Finally, imaging parameters were correlated with clinical severity and somatosensory function. Among predefined pairs, we found only weakly to moderately lower functional connectivity between the right nucleus accumbens and bilateral ventromedial prefrontal cortex in the infra-slow oscillations (ISO) band. The unconstrained ROI-to-ROI analysis revealed lower rsFC between the periaqueductal gray matter (PAG) and left anterior insula, and higher rsFC between the right sensorimotor thalamus and nucleus accumbens. In the correlation analysis, pain was positively associated with insulo-prefrontal rsFC, whereas sensorimotor thalamo-cortical rsFC was positively associated with tactile spatial resolution of the affected side. In contrast to previous reports, we found no group differences for k D or rsFC in the DMN, but detected overall lower data quality in patients. In summary, while some of the previous results were not replicated despite the larger sample size, novel findings from two independent cohorts point to potential down-regulated antinociceptive modulation by the PAG and increased connectivity within the reward system as pathophysiological mechanisms in CRPS. However, in light of the detected systematic differences in data quality between patients and healthy subjects, validity of rsFC abnormalities in CRPS should be carefully scrutinized in future replication studies., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Fatigue affects patients across a variety of neurological diseases, including chronic pain syndromes such as complex regional pain syndrome (CRPS). In CRPS, fatigue is often underestimated, as the focus lies in the assessment and managing of pain and sensorimotor deficits. This study aimed to investigate the prevalence, characteristics, and influence of fatigue on CRPS severity and quality of life in these patients. Such insights could enhance the clinical management of this challenging condition., Methods: In this prospective study, 181 CRPS patients and 141 age and gender-matched individuals with injury but without chronic pain were interviewed using the Fatigue Scale for Motor and Cognitive Function to assess fatigue. Depressive symptoms and quality of life (QoL) were also evaluated as additional outcome measures. Statistical analysis was performed to examine differences in fatigue prevalence between the groups, as well as associations with CRPS severity, pain levels, and clinical phenotype. In addition, best subsets regression was used to identify the primary factors influencing QoL. Fatigue was tested in a mediation analysis as a mediator between pain and depression., Results: CRPS patients showed significantly higher fatigue levels compared to controls (CRPS: 75 [IQR: 57-85] vs. controls: 39 [IQR: 25-57]). Based on the FSMC, 44.2% in the control group experienced fatigue, while 85% of patients with CRPS experienced fatigue (p < 0.001), of which 6% were mild, 15% moderate, and 67% severe. In CRPS severe fatigue was associated with higher pain intensities compared to no fatigue (pain at rest: p = 0.003; pain during movement: p = 0.007) or moderate fatigue (pain during movement: p = 0.03). QoL in our cohort was mainly influenced by pain (pain during movement: adj.R 2  = 0.38; p < 0.001, pain at rest: Δadj.R 2  = 0.02, p = 0.007) and depressive symptoms (Δadj.R 2  = 0.12, p < 0.001). Subsequent analyses indicated that pain and depressive symptoms primarily impact QoL in CPRS whereas fatigue may exert an indirect influence by mediating the connection between pain and depression (p < 0.001)., Conclusions: This pioneering study investigates the prevalence of fatigue in CRPS patients and its relation to disease characteristics. Our results indicate a high prevalence of severe fatigue, strongly correlated with pain intensity, and its importance in the interaction between pain and depression in CRPS. These findings underscore the significant role of fatigue as a disease factor in CRPS. Therefore, the evaluation of CRPS-related disability should include a standardized assessment of fatigue for comprehensive clinical management., (© 2024. The Author(s).)

Purpose: Complex regional pain syndrome (CRPS) is a longstanding condition with spontaneous and evoked pain, that usually occurs in an upper or lower extremity. Although it often resolves within the first year, it may for a minority progress to a chronic and occasionally severely disabling condition. The aim of this study was to explore patients' experiences and perceived effects of a specific treatment, designed for patients with severe and highly disabling CRPS, in order to identify possible treatment-relevant processes., Methods: The method used was a qualitative design, using semi-structured interviews with open-ended questions to capture participants' experiences and perceptions. Ten interviews were analyzed using applied thematic analysis., Results: Despite the fact that participants had a severe conditions, including nerve damage and a long duration of illness, they reported having been helped to increase flexible persistence, reduce fear and avoidance, and improve connections. This helped participants to significant improvements in daily life functioning., Conclusions: The participants described distinct possible treatment-relevant processes leading to a substantial improvement in everyday life. The results imply that there is hope for this group that has been severely disabled for many years. This may help guide future clinical treatment trials.

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., (© 2024. The Author(s).)

Background: Neuroinflammation and maladaptive neuroplasticity play pivotal roles in migraine (MIG), trigeminal autonomic cephalalgias (TAC), and complex regional pain syndrome (CRPS). Notably, CRPS shares connections with calcitonin gene-related peptide (CGRP) in its pathophysiology. This study aims to assess if the documented links between CRPS and MIG/TAC in literature align with clinical phenotypes and disease progressions. This assessment may bolster the hypothesis of shared pathophysiological mechanisms., Methods: Patients with CRPS (n = 184) and an age-/gender-matched control group with trauma but without CRPS (n = 148) participated in this case-control study. Participant answered well-established questionnaires for the definition of CRPS symptoms, any headache complaints, headache entity, and clinical management., Results: Patients with CRPS were significantly more likely to suffer from migraine (OR: 3.23, 95% CI 1.82-5.85), TAC (OR: 8.07, 95% CI 1.33-154.79), or non-classified headaches (OR: 3.68, 95% CI 1.88-7.49) compared to the control group. Patients with MIG/TAC developed CRPS earlier in life (37.2 ± 11.1 vs 46.8 ± 13.5 years), had more often a central CRPS phenotype (60.6% vs. 37.0% overall) and were three times more likely to report allodynia compared to CRPS patients with other types of headaches. Additionally, these patients experienced higher pain levels and more severe CRPS, which intensified with an increasing number of headache days. Patients receiving monoclonal antibody treatment targeting the CGRP pathway for headaches reported positive effects on CRPS symptoms., Conclusion: This study identified clinically relevant associations of MIG/TAC and CRPS not explained by chance. Further longitudinal investigations exploring potentially mutual pathomechanisms may improve the clinical management of both CRPS and primary headache disorders., Trial Registration: German Clinical Trials Register (DRKS00022961)., (© 2023. The Author(s).)

Thoracic outlet syndrome (TOS) and complex regional pain syndrome (CRPS) are two etiologies of chronic pain. TOS is a group of conditions that occur due to compression of the neurovascular structures of the upper extremity while CRPS is a disorder characterized by chronic and unremitting pain. This case highlights the experience of a 22-year-old female who presented following a traumatic injury to her left arm and was initially diagnosed with neurogenic TOS and later CRPS. Over a 10-year-period, she underwent a total of four operations to try and address her debilitating pain. In our third-time reoperation, symptoms of both pathologies nearly completely resolved with extensive neurolysis of the left brachial plexus and application of a scar tissue barrier.

Objective : Severe pain and other symptoms in complex regional pain syndrome (CRPS), such as allodynia and hyperalgesia, are associated with abnormal resting-state brain network activity. No studies to date have examined resting-state brain networks in CRPS patients using electroencephalography (EEG), which can clarify the temporal dynamics of brain networks. Methods : We conducted microstate analysis using resting-state EEG signals to prospectively reveal direct correlations with pain intensity in CRPS patients (n = 17). Five microstate topographies were fitted back to individual CRPS patients' EEG data, and temporal microstate measures were subsequently calculated. Results : Our results revealed five distinct microstates, termed microstates A to E, from resting EEG data in patients with CRPS. Microstates C, D and E were significantly correlated with pain intensity before pain treatment. Particularly, microstates D and E were significantly improved together with pain alleviation after pain treatment. As microstates D and E in the present study have previously been related to attentional networks and the default mode network, improvement in these networks might be related to pain relief in CRPS patients. Conclusions : The functional alterations of these brain networks affected the pain intensity of CRPS patients. Therefore, EEG microstate analyses may be used to identify surrogate markers for pain intensity., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background/importance: Dietary interventions, vitamins, and nutritional supplementation are playing an increasingly important role in the management of neuropathic pain. Current pharmacological treatments are poorly tolerated and ineffective in many cases., Objective: This systematic review aims to study the efficacy of dietary interventions, vitamins, and nutritional supplementation in the management of chronic neuropathic pain in adults., Evidence Review: The review followed PRISMA guidelines and was registered with PROSPERO (#CRD42022300312). Ten databases and gray literature, including Embase.com, MEDLINE and Web of Science, were systematically searched using a combination of keywords and controlled vocabulary related to chronic neuropathic pain and oral non-pharmacological supplements. Studies on adult humans published between 2000 and 2021 were considered for inclusion. The Cochrane Handbook was used to assess risk of bias, and Grading of Recommendations Assessment, Development, and Evaluation was used to determine overall quality of evidence., Findings: Forty studies were included in the final review, and results were categorized according to pain type including pain related to chemotherapy-induced peripheral neuropathy (CIPN, 22 studies, including 3 prospective cohorts), diabetic peripheral neuropathy (DPN, 13 studies, including 2 prospective), complex regional pain syndrome (CRPS-I, 3 studies, including 1 prospective), and other (2 studies, both RCT). The CIPN studies used various interventions including goshajinkigan (4 studies), vitamin E (5), vitamin B12 (3), glutamine (3), N-acetyl-cysteine (2), acetyl-l-carnitine (2), guilongtonluofang (1), ninjin'yoeito (1), alpha-lipoic acid (1), l-carnosine (1), magnesium and calcium (1), crocin (1), and antioxidants (1), with some studies involving multiple interventions. All CIPN studies involved varying cancers and/or chemotherapies, advising caution for generalizability of results. Interventions for DPN included alpha-lipoic acid (5 studies), vitamin B12 (3), acetyl-l-carnitine (3), vitamin E (1), vitamin D (2), and a low-fat plant-based diet (1). Vitamin C was studied to treat CRPS-I (3 studies, including 1 prospective). Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies., Conclusions: Based on the review, we cannot recommend any supplement use for the management of CIPN, although further research into N-acetyl-cysteine, l-carnosine, crocin, and magnesium is warranted. Acetyl-l-carnitine was found to be likely ineffective or harmful. Alpha-lipoic acid was not found effective. Studies with goshajinkigan, vitamin B12, vitamin E, and glutamine had conflicting results regarding efficacy, with one goshajinkigan study finding it harmful. Guilongtonluofang, ninjin'yoeito, and antioxidants showed various degrees of potential effectiveness. Regarding DPN, our review supports the use of alpha-lipoic acid, acetyl-l-carnitine, and vitamin D. The early use of vitamin C prophylaxis for the development of CRPS-I also seems promising. Further research is warranted to confirm these findings., (© 2023 World Institute of Pain.)

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., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The case of a 51-year-old patient with complex regional pain syndrome (CRPS) of the left hand after radius distortion is reported. Anticonvulsant therapy was difficult in this case due to persisting epilepsy with already dual therapy (lamotrigine and brivaracetam) at high dosage. With existing neuropathic pain, pronounced allodynia and hyperhidrosis, repetitive transcutaneous monophasic electrotherapy was applied above the stellate ganglion. A ganglion blockage could not be clinically confirmed in the absence of Horner syndrome, but neuropathic pain and hyperhidrosis could be positively influenced. This case report summarizes the electrode positions used, current parameters, pitfalls and therapy limitations and discusses them in relation to the literature., (© 2022. The Author(s).)

Objective: A potentially useful biomarker for Complex Regional Pain Syndrome (CRPS) is the serum soluble interleukin-2 receptor (sIL-2R) level, which is a marker for T-cell activation. Elevated serum sIL-2R levels have been described in CRPS patients compared to healthy controls. In T-cell mediated inflammatory diseases such as sarcoidosis and rheumatoid arthritis, the serum sIL-2R levels correlate with disease severity. In this study, we investigate whether an association exists between serum sIL-2R levels in CRPS patients and CRPS severity., Methods: A cross-sectional cohort study was conducted in a tertiary pain referral center in the Netherlands. Adult CRPS patients diagnosed by the IASP criteria were included between October 2018 until October 2022. The main study parameters were serum sIL-2R levels and the CRPS severity score., Results: Fifty-three CRPS patients were included with a mean syndrome duration of 84 months (Q3 - Q1:180 - 48). The majority had persistent CRPS with a syndrome duration >1 year (n = 52, 98%). The median pain Numerical Rating Score (NRS) was 7 (Q3 - Q1: 8 - 5) and the mean CRPS severity score was 11 (SD ± 2.3). The median serum sIL-2R level was 330 U/mL (Q3 - Q1:451 - 256). No statistically significant correlation was observed between serum sIL-2R levels and the CRPS severity score (rs = 0.15, P = .28)., Conclusions: Our findings suggest that serum sIL-2R levels cannot be used as a biomarker for syndrome severity in persistent CRPS (syndrome duration >1 year). Serial measurements of serum sIL-2R from early CRPS to persistent CRPS are needed to investigate whether serum sIL-2R levels can be used to monitor T-cell mediated inflammatory syndrome activity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)

Pain and swelling of a limb following creation of arterio-venous fistula (AVF) are often attributable to vascular disorders like venous hypertension or limb ischaemia. Here we report the case of a 70-years old man who developed pain and swelling of upper limb distal to the AVF during second post-operative week due to a complex regional pain syndrome (CRPS). CRPS is characterized by pain that is disproportionate to the invoking injury, autonomic dysfunction, trophic changes and functional impairment of affected limb. Hyperalgesia and allodynia are pain patterns characteristic of CRPS. CRPS has been reported rarely following AVF creation surgery. Prompt diagnosis of CRPS is important to avoid misdiagnosis of vascular disorders and for implementation of right therapeutic strategy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Chronic pain associates with various sleep problems. Patients with complex regional pain syndrome (CRPS) often report impaired sleep, but objective measurements of sleep in CRPS patients are scarce. Neuromodulation with repetitive transcranial magnetic stimulation (rTMS) can alleviate pain and improve sleep. Secondary somatosensory cortex (S2) is a possible rTMS target for the treatment of chronic pain, but the effect of S2-targeted rTMS on sleep is unknown., Methods: This randomized, sham-controlled trial assessed the effect of S2-targeted rTMS on sleep in patients with CRPS. Patients (n = 31) received either S2-targeted rTMS (10 Hz) or sham stimulation for 3 weeks. The effect of treatment on sleep was assessed with validated questionnaires, with a sleep and pain diary, and with a consumer-grade sleep tracker, the Oura ring. In addition to an ordinary univariate analysis of the results, we conducted multivariate testing of the Oura data using linear discriminant analysis (LDA)., Results: S2-targeted rTMS decreased sleep restlessness that significantly differed between the rTMS and sham stimulation patient groups (p = .028). In the multivariate analysis of the Oura data, LDA classification accuracy to separate the rTMS and sham groups exceeded 95% confidence level in four out of the seven tested models. In the subjective evaluation of sleep, the effect of rTMS and sham did not differ., Conclusion: S2-targeted rTMS influenced sleep in patients with CRPS. Improved sleep may enhance CRPS symptom alleviation and be of clinical importance. A univariate analysis could separate the rTMS and sham treatments. The multivariate analysis revealed that including multiple sleep-related parameters can be beneficial when analyzing rTMS effects on sleep. As sleep is related both to pain and quality of life, and sleep rTMS can be directly affected by rTMS, objective monitoring of sleep in various future rTMS trials could be fruitful., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Purpose: This meta-analysis aimed to evaluate the incidence and risk factors for complex regional pain syndrome (CRPS) in radius fractures., Methods: The meta-analysis was performed using the PubMed, Embase, Scopus, and Cochrane Collaboration Library databases. Studies focusing on patients with conservative or surgically treated radius fractures leading to CRPS were included. A control group consisting of patients with radius fractures and no CRPS (-) was included. The outcome measures were incidence and risk factors. Comparative studies were also included. Data were combined using Review Manager 5.4., Results: Out of 610 studies, nine studies were included. The incidence of CRPS after radius fractures ranged from 0.19 to 13.63% (95% CI: 11.12-16.15%). Open fractures, high-energy mechanisms in radial head fractures, and associations with ulnar fractures were risk factors for CRPS [(RR: 0.98; 95% CI: 0.97-1.00), (RR: 0.18; 95% CI: 0.07-0.47), and (RR: 1.25; 95% CI: 1.17-1.35), respectively]. Other risk factors were female sex and high body mass index [(RR: 1.20; 95% CI: 1.05-1.37) and (MD: 1.17; 95% CI: 0.45-1.88)]. Psychiatric factors also increased the incidence of CRPS (RR: 2.04; 95% CI: 1.83-2.28). On the other hand, the type of surgery (external fixation or open reduction and internal fixation) and manipulations; associated comorbidities (diabetes and hypertension) together with tobacco and alcohol abuse; marital status, educational level, employment status, and socioeconomic status were not risk factors (p > 0.05)., Conclusion: The incidence of CRPS in radius fractures was 13.63%. Fractures with greater complexity or greater associated tissue damage, female sex, high BMI, and psychiatric disorders were risk factors for the development of CRPS., Level of Evidence: Meta-analysis of cohort and case series studies; II., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose of Review: The goal of this narrative review is to describe the current understanding of the pathology of Complex Regional Pain Syndrome (CRPS), as well as diagnostic standards and therapeutic options. We will then make the case for early recognition and management., Recent Findings: CRPS remains an enigmatic pain syndrome, comprising several subtypes. Recent recommendations clarify diagnostic ambiguities and emphasize the importance of standardized assessment and therapy. Awareness of CRPS should be raised to promote prevention, early detection, and rapid escalation of therapy in refractory cases. Comorbidities and health costs (i.e., the socioeconomic impact) must also be addressed early to prevent negative consequences for patients., (© 2023. The Author(s).)

Background: Complex regional pain syndrome (CRPS) is a chronic neuropathic painful condition, sometimes associated with spinal myoclonus. For intractable cases spinal cord stimulation is an important modality of treatment but the response of specifically myoclonus to this treatment is not well described., Case Description: A 40-year old male, had a history of trauma 12 years back since when he had intractable neuropathic pain in his both upper limbs with superimposed severely disabling myoclonic jerks. He had been through multiple treatment failures. We inserted a cervical spinal cord stimulator which led to immediate cessation of myoclonic jerks, with significant improvement in visual analogue score and Oswestry disability index., Conclusion: In patients of chronic intractable cervico-brachial pain disorder with superimposed myoclonus, cervical spinal cord stimulation may be effective against the myoclonus as well as the pain.

Objective: The objective was to investigate the efficacy and safety of soticlestat as adjunctive therapy in participants with complex regional pain syndrome (CRPS)., Design: A proof-of-concept phase 2a study, comprising a 15-week randomized, double-blind, placebo-controlled, parallel-group study (part A), and an optional 14-week open-label extension (part B)., Methods: Twenty-four participants (median age 44.5 years [range, 18-62 years]; 70.8% female) with chronic CRPS were randomized (2:1) to receive oral soticlestat or placebo. Soticlestat dosing started at 100 mg twice daily and was titrated up to 300 mg twice daily. In part B, soticlestat dosing started at 200 mg twice daily and was titrated up or down at the investigator's discretion. Pain intensity scores using the 11-point Numeric Pain Scale (NPS) were collected daily. The Patient-Reported Outcomes Measurement Information System (PROMIS)-29, Patients' Global Impression of Change (PGI-C), and CRPS Severity Score (CSS) were completed at screening and weeks 15 and 29., Results: From baseline to week 15, soticlestat treatment was associated with a mean change in 24-hour pain intensity NPS score (95% confidence interval) of -0.75 (-1.55, 0.05) vs -0.41 (-1.41, 0.59) in the placebo group, resulting in a non-significant placebo-adjusted difference of -0.34 (-1.55, 0.88; P = .570). Statistically non-significant numerical changes were observed for the PROMIS-29, PGI-C, and CSS at weeks 15 and 29., Conclusions: Adjunctive soticlestat treatment did not significantly reduce pain intensity in participants with chronic CRPS., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)

Introduction This paper describes the epidemiology and clinical presentation of complex regional pain syndrome (CRPS) in a large, integrated health care delivery system; and CRPS incidence rates (IRs) over a time period spanning human papillomavirus (HPV) vaccine licensure and published case reports of CRPS following HPV vaccination. Methods The authors examined CRPS diagnoses in patients aged 9-30 years between January 2002 and December 2017 using electronic medical records, excluding patients with lower limb diagnoses only. Medical record abstraction and adjudication were conducted to verify diagnoses and describe clinical characteristics. CRPS IRs were calculated for 3 periods: Period 1 (2002-2006: before HPV vaccine licensure), Period 2 (2007-2012: after licensure but before published case reports), and Period 3 (2013-2017: after published case reports). Results A total of 231 individuals received an upper limb or unspecified CRPS diagnosis code during the study period; 113 cases were verified through abstraction and adjudication. Most verified cases (73%) were associated with a clear precipitating event (eg, non-vaccine-related injury, surgical procedure). The authors identified only 1 case in which a practitioner attributed CRPS onset to HPV vaccination. Twenty-five incident cases occurred in Period 1 (IR = 4.35/100,000 person-years (PY), 95% confidence interval (CI) = 2.94-6.44), 42 in Period 2 (IR = 5.94/100,000 PY, 95% CI = 4.39-8.04), and 29 in Period 3 (IR = 4.53/100,000 PY, 95% CI = 3.15-6.52); differences between periods were not statistically significant. Conclusion These data provide a comprehensive assessment of the epidemiology and characteristics of CRPS in children and young adults and provide further reassurance about the safety of HPV vaccination., Competing Interests: Conflicts of InterestDr Naleway reports receiving research funding from Pfizer and Vir Biotechnology for unrelated studies. Dr Mittendorf reports support from institutional funding from GE Healthcare. The other authors have no conflicts of interest.

This is a narrative review of intravenous ketamine infusions for the treatment of complex regional pain syndrome (CRPS). It briefly covers the definition of CRPS, its epidemiology, and other treatments before introducing ketamine as the article's focus. A summary of ketamine's evidence base and its mechanisms of action is provided. The authors then review ketamine dosages reported in peer-reviewed literature for the treatment of CRPS, and their associated duration of pain relief. The observed response rates to ketamine and predictors of treatment response are also discussed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Complex regional pain syndrome (CRPS) is a chronic pain condition of an extremity. While achieving pain relief in CRPS is challenging, esketamine infusions can accomplish pain relief for several weeks post-infusion in a subgroup of CRPS patients. Unfortunately, CRPS esketamine protocols are very heterogeneous in advice on dosage, administration and treatment setting. Currently, no trials are available that study differences between intermittent and continuous esketamine infusions for CRPS. With the current situation of bed shortages, it is difficult to admit patients for several consecutive days for inpatient esketamine treatments. In this study, we investigate whether 6 intermittent outpatient esketamine treatments are not inferior to a continuous 6-day inpatient esketamine treatment in establishing pain relief. In addition, several secondary study parameters will be assessed in order to investigate mechanisms responsible for pain relief by esketamine infusions. Furthermore, the cost-effectiveness will be analyzed., Methods: In this RCT, the primary objective is to demonstrate that an intermittent esketamine dosing regimen is non-inferior to a continuous esketamine dosing regimen at 3 months follow-up. We will include 60 adult CRPS patients. The inpatient treatment group receives a continuous intravenous esketamine infusion for 6 consecutive days. The outpatient treatment group receives a 6-hour intravenous esketamine infusion every 2 weeks for 3 months. Esketamine dose will be individually tailored and is started at 0.05 mg/kg/h and can be increased to a maximum of 0.2 mg/kg/h. Each patient will be followed for 6 months. The primary study parameter is perceived pain intensity, measured by an 11-point Numerical Rating Scale. Secondary study parameters are conditioned pain modulation, quantitative sensory testing, adverse events, thermography, blood inflammatory parameter, questionnaires about functionality, quality of life and mood and costs per patient., Discussion: If our study reveals non-inferiority between intermittent and continuous esketamine infusions, these findings can be beneficial to increase the availability and flexibility of esketamine infusions through outpatient treatments. Furthermore, the costs of outpatient esketamine infusions could be lower than inpatient esketamine infusions. In addition, secondary parameters may predict response to esketamine treatment., Trial Registration: ClinicalTrials.gov Identifier NCT05212571 , date of registration 01-28-2022., Protocol Version: Version 3, February 2022., (© 2023. The Author(s).)

Introduction: Complex regional pain syndrome (CRPS) is characterized by nociplastic pain with alterations in sympathetic function. Neuromodulation could be a useful alternative therapy option. Dorsal root ganglion (DRG) stimulation has demonstrated better results than conventional spinal cord stimulation (SCS) for patients with CRPS in lower limbs., Methods: We report a case series of seven patients treated with cervical DRG stimulation for CRPS of the hand that required neuromodulation for pain relief, after no response with other analgesic techniques (medication and interventional). We report retrospective data collection of seven consecutive patients with a 1-year follow-up., Results: Seven patients were trialed, and six were implanted with a permanent pulse generator after achieving more than 50% pain relief during 2-7 days of trial phase. The average pain relief (rated on a standard 100 mm visual analog scale) after 1 year of treatment was 64.3% ± 16.6. No major complications were observed during a 1-year follow-up., Discussion: The results for cervical DRG stimulation are similar to other DRG stimulation studies for the treatment of refractory CRPS at lower levels. The cervical DRG implant technique guided with C-arm fluoroscopy and under conscious sedation could be a safe and effective option for relieving pain of the upper limbs CRPS. Monitoring neural status is required for cervical DRG stimulation either with a responder awake patient or with intraoperative neural monitoring in non-responder patients., (© 2022 World Institute of Pain.)

Spinal cord stimulation is a successful and thoroughly documented procedure in treating chronic refractory pain. Complications are rare and usually mild, but hardware complications such as electrode dysfunction have been shown to be detrimental in treatment efficacy and patient outcome. We report a case in which a patient diagnosed with complex regional pain syndrome underwent spinal cord stimulation for pain management and experienced lead migration and fracture, resulting in loss of paresthesia and increased pain. This case provides useful clinical information on identifying electrode dysfunction in patients with implanted spinal cord stimulators and emphasizes the importance of preventative measures to reduce the risk of similar complications.

A retrospective data analysis of 159 complex regional pain syndrome (CRPS) patients (n = 116 women, 73.0%, mean age 60.9 ± 14.4 years; n = 43 men, 27.0%, mean age 52.3 ± 16.7 years) was performed from 2009 to 2020. The right side was affected in 74 patients (46.5%), the left in 84 patients (52.8%), and 1 patient (0.7%) developed a bilateral CRPS. Data were analyzed for the frequency and distribution of symptoms. The number of reduction maneuvers and the number of Budapest criteria were compared in relation to the severity of CRPS. Hand and wrist (n = 107, 67.3%), followed by foot and ankle (n = 36, 22.6%) and other locations (n = 16, 10.1%) were mainly affected by CRPS. The main causes included direct trauma (n = 120, 75.5%), surgery without previous trauma (n = 25, 15.7%), other causes (n = 9, 5.7%), and spontaneous development (n = 3, 1.9%); there was also missing documentation (n = 2, 1.3%). The most common symptoms were difference in temperature (n = 156, 98.1%), limitation of movement (n = 149, 93.7%), and swelling (n = 146, 91.8%). There was no correlation between the number of reduction maneuvers and the number of Budapest criteria. In summary, patients with the following constellation are at increased risk of CRPS: a female, over 60 years old, who has fallen and has sustained a fracture in the hand or wrist with persistent pain and has been immobilized with a cast for approx. 4 weeks.

We describe the case of a 17-year-old woman diagnosed with complex regional pain syndrome (CRPS) at a pain clinic after the second dose of the COVID-19 vaccine. She was referred to our department for surgical treatment of movement disorder seven months after the second inoculation. Baclofen (50 µg), administered intrathecally, improved the involuntary movements of her right hand. After administration of zolpidem (5 mg), involuntary movements of the right index finger almost disappeared. However, neither zolpidem nor intrathecal baclofen improved the limited range of motion of the first joint of the left-hand finger. Despite various reports on CRPS development after vaccination, only one case post COVID-19 vaccination has been reported. Therefore, healthcare providers should keep in mind that CRPS can appear after the COVID-19 vaccination., Competing Interests: Declarations of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Neuroinflammatory mechanisms and maladaptive neuroplasticity underlie the progression of complex regional pain syndrome (CRPS), which is prototypical of central neuropathic pain conditions. While cortical maladaptive alterations are well described, little is known about the contribution of the brainstem to the pathophysiology. This study investigates the role of pain-modulatory brainstem pathways in CRPS using the nociceptive blink reflex (nBR), which not only provides a direct read-out of brainstem excitability and habituation to painful stimuli but may also be suitable for use as a diagnostic biomarker for CRPS. Thirteen patients with CRPS and thirteen healthy controls (HCs) participated in this prospective case-control study investigating the polysynaptic trigemino-cervical (R2) nBR response. The R2 area and its habituation were assessed following repeated supraorbital electrical stimulation. Between-group comparisons included evaluations of diagnostic characteristics as a potential biomarker for the disease. Patients with CRPS showed a substantial decrease in habituation on the stimulated (Cohen's d: 1.3; p = 0.012) and the non-stimulated side (Cohen's d: 1.1; p = 0.04). This is the first study to reveal altered nBR habituation as a pathophysiological mechanism and potential diagnostic biomarker in CRPS. We confirmed previous findings of altered nBR excitability, but the diagnostic accuracy was inferior. Future studies should investigate the nBR as a marker of progression to central mechanisms in CRPS and as a biomarker to predict treatment response or prognosis.

Movement limitation is a common characteristic of chronic pain such that pain prevents the very movement and activity that is most likely to promote recovery. This is particularly the case for pathological pain states such as complex regional pain syndrome (CRPS). One clinical approach to CRPS that has growing evidence of efficacy involves progressive movement imagery training. Graded Motor Imagery (GMI) targets clinical and neurophysiological effects through a stepwise progression through implicit and explicit movement imagery training, mirror therapy and then functional tasks. Here we review experiences from over 20 years of clinical and research experience with GMI. We situate GMI in terms of its historical underpinnings, the benefits and outstanding challenges of its implementation, its potential application beyond CRPS. We then review the neuropathological targets of GMI and current thought on its effects on neurophysiological biomarkers. PERSPECTIVE: This article provides an overview of our experiences with graded motor imagery training over the last 20 years focussing on the treatment of CRPS. It does both cover the theoretical underpinnings for this treatment approach, biomarkers which indicate potential changes driven by GMI, and experiences for achieving optimal treatment results., (Copyright © 2022 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Both nerve injury and complex regional pain syndrome (CRPS) can result in chronic pain. In traumatic neuropathy, the blood nerve barrier (BNB) shielding the nerve is impaired-partly due to dysregulated microRNAs (miRNAs). Upregulation of microRNA-21-5p (miR-21) has previously been documented in neuropathic pain, predominantly due to its proinflammatory features. However, little is known about other functions. Here, we characterized miR-21 in neuropathic pain and its impact on the BNB in a human-murine back translational approach. MiR-21 expression was elevated in plasma of patients with CRPS as well as in nerves of mice after transient and persistent nerve injury. Mice presented with BNB leakage, as well as loss of claudin-1 in both injured and spared nerves. Moreover, the putative miR-21 target RECK was decreased and downstream Mmp9 upregulated, as was Tgfb. In vitro experiments in human epithelial cells confirmed a downregulation of CLDN1 by miR-21 mimics via inhibition of the RECK/MMP9 pathway but not TGFB. Perineurial miR-21 mimic application in mice elicited mechanical hypersensitivity, while local inhibition of miR-21 after nerve injury reversed it. In summary, the data support a novel role for miR-21, independent of prior inflammation, in elicitation of pain and impairment of the BNB via RECK/MMP9., (© 2022 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.)

This paper presents the application of an adaptive exoskeleton for finger rehabilitation. The system consists of a force-controlled exoskeleton of the finger and wireless coupling to a mobile application for the rehabilitation of complex regional pain syndrome (CRPS) patients. The exoskeleton has sensors for motion detection and force control as well as a wireless communication module. The proposed mobile application allows to interactively control the exoskeleton, store collected patient-specific data, and motivate the patient for therapy by means of gamification. The exoskeleton was applied to three CRPS patients over a period of six weeks. We present the design of the exoskeleton, the mobile application with its game content, and the results of the performed preliminary patient study. The exoskeleton system showed good applicability; recorded data can be used for objective therapy evaluation.

We treated a 51-year-old woman with refractory Complex Regional Pain Syndrome type I (CRPS-I) involving her left hand and forearm with subcutaneous injections of BoNT/A. The injections were performed every 3 months, with a total of six treatments. Each treatment was able to effectively improve pain and motor impairment; however, the duration of the effect was limited to only a few months. BoNT/A could improve patients' quality of life with CRPS; however, extensive clinical studies are needed to determine its role in clinical practice.

There have been some modest recent advancements in the research of Complex Regional Pain Syndrome, yet the amount and quality of the work in this complicated multifactorial disease remains low (with some notable exceptions; e.g., the recent work on the dorsal root ganglion stimulation). The semi-systematic (though in some cases narrative) approach to review is necessary so that we might treat our patients while waiting for "better research." This semi-systematic review was conducted by experts in the field, (deliberately) some of whom are promising young researchers supplemented by the experience of "elder statesman" researchers, who all mention the system they have used to examine the literature. What we found is generally low- to medium-quality research with small numbers of subjects; however, there are some recent exceptions to this. The primary reason for this paucity of research is the fact that this is a rare disease, and it is very difficult to acquire a sufficient sample size for statistical significance using traditional statistical approaches. Several larger trials have failed, probably due to using the broad general diagnostic criteria (the "Budapest" criteria) in a multifactorial/multi-mechanism disease. Responsive subsets can often be identified in these larger trials, but not sufficient to achieve statistically significant results in the general diagnostic grouping. This being the case the authors have necessarily included data from less compelling protocols, including trials such as case series and even in some instances case reports/empirical information. In the humanitarian spirit of treating our often desperate patients with this rare syndrome, without great evidence, we must take what data we can find (as in this work) and tailor a treatment regime for each patient., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)

Despite increasing research, the pathophysiology of Complex Regional Pain Syndrome (CRPS) remains poorly understood. Due to its easy accessibility, the skin represents an ideal approach to gain a better understanding of the underlying processes. We conducted a systematic review of original studies investigating potential biomarkers cutaneous biomarkers in CRPS. Original articles with a minimum level IV of evidence were screened using the following databases: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Web of Science Core Collection. Quality assessment was performed using the Methodological Index for Non-Randomized Studies criteria. A total of 11 studies exploring cutaneous biomarkers in 299 CRPS Type I patients were included. The biomarkers identified revealed implications of the following pathophysiological processes: inflammation via interleukins and TNF-a, vascular dysregulation (ET-1/NOx disturbances and hypoxia-high lactate), small fiber neuropathy and hypersensitivity. In terms of skin morphology, evidence suggests: neurite loss, increased expression and disturbed migration of mast cells, as well as an increased expression of α1-adrenoceptors on keratinocytes. The data supporting hypersensitivity had a high risk of bias on quality assessment. The current review has emphasized the current state of knowledge regarding the cutaneous biomarkers in patients suffering from CRPS Type I. Our results serve as a basis for future developments of techniques that would either facilitate diagnosis or may represent therapeutic targets. Trial registration PROSPERO: CRD42020203405. Level of evidence: IV (Systematic Review)., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Complex Regional Pain Syndrome (CRPS) is an invalidating chronic condition that can occur after an acute peripheral lesion. Prism adaptation therapy is regarded as a promising tool to improve chronic pain in this syndrome but the mechanisms which lead to pain amelioration remain unknown. In this exploratory report we performed a retrospective analysis of longitudinal data collected from a single, atypical patient, who showed hyper-attention toward her affected (left) hand. Repeated assessments of pain and spatial neglect made during the course of the prism adaptation treatment revealed differential contributions of the two hands to adaptation-induced pain reduction. Treatment response appeared to be associated with a relative modification of the spatial behaviour of the two hands. This case study provides a new example of pain relief following prismatic deviation away from the pathological side.

Background: Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by autonomic and inflammatory features. There is paucity of data regarding sustained benefits of any treatment modality. We aimed to document the effect of steroids in CRPS on long-term basis., Materials and Methods: We came across five patients of CRPS in Out Patient clinics of super-speciality Institutes in North India. All five cases fulfilled the Budapest criteria for the diagnosis of CRPS. All of them received prednisolone and were prospectively followed up for 2 years. Treatment outcome was carefully recorded in all affected modalities., Results: All five cases were found to have excruciating neuropathic pain in defined regions along with cutaneous manifestations. Osseous changes in the form of surface erosion of underlying bones in four cases and marked marrow edema leading to considerable increase in bone thickness in one case were noted. All these features improved considerably following steroid therapy. Bone marrow edema and bone resorption showed improvement on serial imaging., Conclusion: Apart from pain relief, steroids therapy is capable of reversing the osteo-cutaneous autonomic changes of CRPS type I., Competing Interests: None

We present the acute worsening of clinical presentation in complex regional pain syndrome (CRPS), following mRNA-based COVID-19 vaccination. We report the case series of three patients diagnosed with CRPS type I who presented with acute worsening of symptoms after mRNA-based COVID-19 vaccination and their medical management. The acute clinical worsening after mRNA-based COVID-19 vaccination was transient and effectively managed with adjustment of individualized therapy in all three patients. The mortality and morbidity of COVID-19 infection are serious, and vaccination is recommended in the general population, including patients with a diagnosis of CRPS. However, clinicians should be aware of the possibility that there may be a clinical worsening CRPS after mRNA-based COVID-19 vaccination.

Background: Complex regional pain syndrome (CRPS) is a neuropathic pain condition with no universally recognised treatment. The study evaluates the efficacy of a therapeutic protocol consisting of oral citalopram and lidocaine injections in patients affected by CRPS., Methods: Between January 2010 and December 2014, 150 consecutive patients with CRPS were enrolled in the study and randomly assigned into three groups: group one - lidocaine injection and oral citalopram; group two - lidocaine injection and oral placebo; and group three - injective and oral placebo. The Impairment Sum Score (ISS) was used to assess the severity of CRPS before, as well as at regular intervals after treatment commenced. Statistical significance (p < 0.05) was determined by paired t-tests., Results: The combined treatment proved to be more effective (ISS 47.6 to 12.6) than local anaesthetic alone (ISS 47.5 to 21.5) and to placebo (ISS 47.2 to 29.9)., Conclusion: This study indicates that CRPS may be managed with well-tolerated association of oral citalopram and lidocaine injections., (Copyright © 2021 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Complex Regional Pain Syndrome (CRPS) is a chronic, disabling condition with prolonged or excessive pain persisting in a limb usually following a triggering injury or trauma to an extremity. The subjective expression of pain is disproportionate to what would be objectively expected from the initial injury. It may also be accompanied by a variety of autonomic disturbances and trophic abnormalities such as swelling in the affected area and changes in skin color and temperature. Understanding the pathophysiology of CRPS remains a medical challenge, along with making the diagnosis and devising an effective treatment plan. There are limited randomized controlled trials and definitive treatment is yet to evolve for this life-altering condition. This case study illustrates the safe, cost-effective addition and efficacious use of hypnosis in the integrative treatment plan for a teenager with CRPS.

Local tissue ischemic hypoxia is a peripheral process that can be targeted with topical treatment to alleviate pain under chronic pain conditions such as complex regional pain syndrome (CRPS) and peripheral neuropathic pain. We recently reported three novel salts and a co-crystal composed of vasoactive agents and antioxidant nutraceuticals, all of which produced potent topical anti-allodynic effects in the chronic postischemic pain (CPIP) rat model of CRPS. One of the products, pentx-pca, is a co-crystal synthesized from pentoxifylline (pentx) and protocatechuic acid (pca). Pentx-pca exhibited potent topical anti-allodynic effects in CPIP and rats with chronic constriction injury of the sciatic nerve exceeding effects produced individually by pentx and pca. We hypothesized that the anti-allodynic effects of pentx-pca in CPIP rats were due to its impact on local tissue oxygenation and subsequent oxygen-dependent mitochondrial respiration. Percutaneous tissue oxygen saturation (SaO 2 ) measurements taken from the hind paw of the CPIP rats revealed that anti-allodynic doses of topical pentx-pca increased local tissue SaO 2 . Moreover, assessment of the oxygen-dependent mitochondrial function using a triphenyl tetrazolium chloride assay revealed that mitochondrial dysfunction significantly declined in the plantar muscle collected from CPIP rats topically treated with anti-allodynic doses of pentx-pca as compared to vehicle-treated CPIP rats. Furthermore, time-dependent resolution of plantar muscle mitochondrial dysfunction, that occurred in the CPIP rats at 6-week post procedure, paralleled the loss of the anti-allodynic response to topical treatment with pentx-pca. Our results indicated that pentx-pca produced potent anti-allodynic effects in the CPIP rat model of CRPS by alleviating peripheral tissue ischemia/hypoxia and downstream hypoxia-driven mitochondrial dysfunction.

Complex regional pain syndrome (CRPS) has never comprehensively been examined from a lived experience perspective. Patients generally have a poorer quality of life than people with other chronic pain conditions. This study aimed to understand the essence of living with CRPS. Data were collected from 17 patients via in-depth interviews. Hermeneutic discussions with four health professionals generated deeper insights. Internet blogs and a book containing patient stories were included for theme verification and triangulation. CRPS is seen as a war-like experience and five themes were identified within the battle: "dealing with the unknown enemy", "building an armoury against a moving target", "battles within the war", "developing battle plans with allies" and "warrior or prisoner of war". Patients live with a chronic pain condition and experience problems unique to CRPS such as fear of pain extending to other parts of their body. Use of the model generated by this research may assist patient/clinician interactions and guide therapeutic discussions. Support for people living with CRPS does not always exist, and some healthcare professionals require additional education about the condition. Better health outcomes are experienced by patients when their personal situation and experiences are heard and understood by health care professionals. PERSPECTIVE: This article presents the lived experience of CRPS. This information and the model generated can help clinicians to better understand their patients and deliver appropriate patient-centered care., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess thermal-sensory thresholds and psychosocial factors in children with Complex Regional Pain Syndrome Type 1 (CRPS-I) compared to healthy children., Methods: We conducted quantitative sensory testing on 34 children with CRPS-I and 56 pain-free children. Warm, cool, heat, and cold stimuli were applied to the forearm. Children with CRPS-I had the protocol administered to the pain site and the contralateral-pain site. Participants completed the self-report Behavior Assessment System for Children., Results: Longer pain durations (>5.1 months) were associated with decreased sensitivity to cold pain on the pain site ( P = .04). Higher pain-intensity ratings were associated with elevated anxiety scores ( P = .03). Anxiety and social stress were associated with warmth sensitivity (both P < .05) on the contralateral-pain site., Conclusions: Pain duration is an important factor in assessing pediatric CRPS-I. Hyposensitivity in the affected limb may emerge due to degeneration of nociceptive nerves. Anxiety may contribute to thermal-sensory perception in childhood CRPS-I.

Body perceptual disturbances are an increasingly acknowledged set of symptoms and possible clinical markers of complex regional pain syndrome (CRPS), but the neurophysiological and neurocognitive changes that underlie them are still far from being clear. We adopted a multivariate and neurodynamical approach to the analysis of EEG modulations evoked by touch to highlight differences between patients and healthy controls, between affected and unaffected side of the body, and between "passive" (i.e., no task demands and equiprobable digit stimulation) and "active" tactile processing (i.e., where a digit discrimination task was administered and spatial probability manipulated). When correct identifications are considered, an early reduction in cortical decodability (28-56 ms) distinguishes CRPS patients from healthy volunteers. However, when error trials are included in the classifier's training, there is an unexpected increased decodability in the CRPS group compared with healthy volunteers (280-320 ms). These group differences in neural processing seemed to be driven by the affected rather than the unaffected side. We corroborated these findings with several exploratory analyses of neural representation dynamics and behavioural modelling, highlighting the need for single participant analyses. Although several limitations impacted the robustness and generalizability of these comparisons, the proposed analytical approach yielded promising insights (as well as possible biomarkers based on neural dynamics) into the relatively unexplored alterations of tactile decision-making and attentional control mechanisms in chronic CRPS., (© 2021 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Introduction: Complex regional pain syndrome (CRPS), formerly known as reflex sympathetic dystrophy (RSD), is a difficult to treat condition characterized by debilitating pain and limitations in functional ability. Neuromodulation, in the form of spinal cord stimulation (SCS) and peripheral nerve stimulation (PNS), have been traditionally used as a treatment for CRPS with variable success., Objective: This chart review describes the use of implantable PNS systems in the treatment of CRPS of the upper and lower extremities spanning nearly three decades., Materials and Methods: A retrospective chart review was performed on 240 patients with PNS implanted between 1990 and 2017 at our institution. Of these, 165 patients were identified who had PNS systems implanted for a diagnosis of CRPS. Patient profile, including baseline characteristics, comorbidities, past/current interventions/medications and targeted nerves, was descriptively summarized through standard summary statistics. Patients' pain scores and opioid consumptions at baseline (preimplant), 1 month, 6 months, and 12 months were collected and compared. Device revisions and explants were summarized, and patient functional outcomes were described., Results: Pain scores at baseline and at 12-month follow-up were decreased from a mean of 7.4 ± 1.6 to 5.5 ± 2.4 and estimated to be 1.87 (95% CI: [1.29, 2.46], paired t-test p-value <0.001) lower at 12 months. At baseline, 62% of patients were on chronic opioid therapy, compared with 41% at 12 months. Of 126 patients who reported changes in functional status, 64 (51%) reported improvement, 27 (21%) reported worsening, and 35 (28%) did not report any meaningful change. Excluding end-of-life battery replacements, surgical revision occurred in 56 (34%) of patients. Thirteen patients (8%) underwent implantation of a second PNS because of symptomatic expansion outside of the original painful region. Device explant was performed in 32 (19%) of patients. Median length of follow-up was 74 [14, 147] months. Of the 36 patients who continue to follow-up at our institution, 29 (81%) continue to use their PNS., Conclusions: We can conclude that PNS is a useful modality to improve function and reduce long-term pain in selected patients suffering from CRPS type I and type II., (© 2020 International Neuromodulation Society.)

Background: Human hairy (not glabrous skin) is equipped with a subgroup of C-fibers, the C-tactile (CT) fibers. Those do not mediate pain but affective aspects of touch. CT-fiber-activation reduces experimental pain if they are intact. In this pilot study we investigated pain modulating capacities of CT-afferents in CRPS., Methods: 10 CRPS-patients (mean age 33 years, SEM 3.3) and 11 healthy controls (mean age 43.2 years, SEM 3.9) participated. CT-targeted-touch (brush stroking, velocity: 3 cm/s) was applied on hairy and glabrous skin on the affected and contralateral limb. Patients rated pleasantness of CT-targeted-touch (anchors: 1 "not pleasant"-4 "very pleasant") twice daily on 10 days. Pain intensity (NRS: 0 "no pain" - 10 "worst pain imaginable") was assessed before, 0, 30, 60 and 120 min after each CT-stimulation. To assess sensory changes, quantitative-sensory-testing was performed at the beginning and the end of the trial period., Results: CT-targeted-touch was felt more pleasant on the healthy compared to the affected limb on hairy (p < 0.001) and glabrous skin (p 0.002), independent of allodynia. In contrast to healthy controls patients felt no difference between stimulating glabrous and hairy skin on the affected limb. Thermal pain thresholds increased after CT-stimulation on the affected limb (cold-pain-threshold: p 0.016; heat-pain-threshold: p 0.033)., Conclusions: CT-stimulation normalizes thermal pain thresholds but has no effect on the overall pain in CRPS. Therefore, pain modulating properties of CT-fibers might be too weak to alter chronic pain in CRPS. Moreover, CT-fibers appear to lose their ability to mediate pleasant aspects of touch in CRPS., (© 2021. The Author(s).)

It has been suggested that sensorimotor conflict contributes to the maintenance of some pathological pain conditions, implying that there are problems with the adaptation processes that normally resolve such conflict. We tested whether sensorimotor adaptation is impaired in people with Complex Regional Pain Syndrome (CRPS) by characterising their adaption to lateral prismatic shifts in vision. People with unilateral upper-limb CRPS Type I (n = 17), and pain-free individuals (n = 18; matched for age, sex, and handedness) completed prism adaptation with their affected/non-dominant and non-affected/dominant arms. We examined 1) the rate at which participants compensated for the optical shift during prism exposure (i.e., strategic recalibration), 2) endpoint errors made directly after prism adaptation (sensorimotor realignment) and the retention of these errors, and 3) kinematic markers associated with strategic control. Direct comparisons between people with CRPS and controls revealed no evidence of any differences in strategic recalibration, including no evidence for differences in a kinematic marker associated with trial-by-trial changes in movement plans during prism exposure. All participants made significant endpoint errors after prism adaptation exposure, indicative of sensorimotor realignment. Overall, the magnitude of this realignment did not differ between people with CRPS and pain-free controls. However, when endpoint errors were considered separately for each hand, people with CRPS made greater errors (indicating more rather than less realignment) when using their affected hand than their non-affected hand. No such difference was seen in controls. Taken together, these findings provide no evidence of impaired strategic control or sensorimotor realignment in people with CRPS. In contrast, they provide some indication that there could be a greater propensity for sensorimotor realignment in the CRPS-affected arm, consistent with more flexible representations of the body and peripersonal space. Our study challenges an implicit assumption of the theory that sensorimotor conflict might underlie some pathological pain conditions., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Complex regional pain syndrome, CRPS, occurs with severe disabling pain, usually in the leg or hand, coupled with changes in pain perception, hyperesthesia and allodynia. There is as well, edema, changes in the color of the skin, trophic changes, and dystonia. The pain syndrome is often triggered by minor trauma. The pain perception is severe and out of context with the initial trauma. The syndrome is rare, occurring in a population-based study in the United States, with an incidence of only 5.5 per hundred thousand people per year. The incidence in Iceland, from the National Register of Diseases from the Directorate of Health, was 1.3 per annum, per hundred thousand people. The exact etiology of the disease is unknown. It is presumed that inflammation is the cause, often resulting from an autoimmune reaction. The term pain sensitization is also used to describe the pain mechanism, both in peripheral nerves and in the central nervous system. There are changes and displacement of the area of the neocortex that is coupled with pain perception. The criteria of the International Association for the Study of Pain (IASP) were the basis for the diagnosis. Interdisciplinary team management according to the biopsychosocial model is thought to be the preferred treatment approach. The members of the team are occupational therapists, physiotherapists, social workers, psychologists, nurses, and medical doctors, augmented by other disciplines as needed. One treatment option is mirror therapy, where the diseased extremity is held behind a mirror during the training and the patient observes movements of the healthy extremity. Initially treatment is aimed at treating the inflammation, often with NSAID drugs, or with steroids. Medical treatments are the same as apply for the treatment of neural pain, with drugs such as Gabapentin, or anti depressive agents as duloxetine or imipramine. There is an indication to use bisphosphonates such as alendronate, especially if there is osteoporosis. It is assumed that the function of the NMDA receptor has changed in the central nervous system and treatment with intravenous ketamine, is an option. Spinal cord stimulation of the dorsal horns of the spine has been effective as well. In majority of cases the syndrome resolves in the first two years, but for the rest the prognosis is dire, symptoms getting worse and persisting for years and even decades.

Background: Complex regional pain syndrome (CRPS) is a rare and severe chronic pain condition, with effective treatment options not established for many patients. The underlying pathophysiology remains unclear, but there is a growing appreciation for the role of central mechanisms which have formed the basis for brain-based therapies such as transcranial magnetic stimulation and mirror visual feedback (MVF). MVF has been deployed in the treatment of CRPS using both conventional mirrors and virtual reality (VR)., Objective: The aim of this study was to further investigate the use of VR in the treatment of patients with unilateral upper limb CRPS. VR has the potential advantage of more flexible and more motivating tasks, as well as the option of tracking patient improvement through the use of movement data., Methods: We describe the development, acceptability, feasibility, and usability of an open-source VR program MVF module designed to be used with consumer VR systems for the treatment of CRPS. The development team was an interdisciplinary group of physical therapists, pain researchers, and VR researchers. Patients recruited from a pain clinic completed 3-5 visits each to trial the system and assessed their experiences in pre- and post-treatment questionnaires., Results: All 9 (100%) participants were able to use the system for 3, 4, or 5 trials each. None of the participants quit any trial due to cybersickness. All 9 (100%) participants reported interest in using the module in the future. Participants' reported average pain scores in the affected limb were not significantly different from baseline during treatment or after treatment (P=.16). We did not find a statistically significant effect on participants' self-reported average pain scores., Conclusions: We propose that this module could be a useful starting point for modification and testing for other researchers. We share modifications to make this module usable with standalone headsets and finger tracking. Next steps include adapting this module for at-home use, or for use with participants with lower limb pain., (©Andrea Stevenson Won, Ariana C Barreau, Mark Gaertner, Tristan Stone, Joshua Zhu, Cheng Yao Wang, Sean Mackey. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 26.05.2021.)

Background: Systemic vitamin C supplementation after wrist fracture has been suggested to reduce the incidence of complex regional pain syndrome (CRPS). This study aimed to evaluate the effect of regional vitamin C in Bier block in the early phase of fracture on CRPS occurrence following surgery for distal radius fractures., Methods: Seventy-four patients with isolated extra-articular distal radius fracture with the plan of fixation under Bier block were enrolled. Patients were assigned randomly into two groups: receiving either 500 mg vitamin C or sterile water as a Bier block adjuvant. Both groups received 500 mg of oral vitamin C for six weeks. The patients were evaluated for CRPS signs and symptoms at 2, 4, 6, and 12 weeks post-surgery., Results: The overall incidence of CRPS 12 weeks after surgery in the vitamin C group was significantly less than the controls (22.9% vs 45.5%, p = 0.04). Logistic regression analysis showed that the only significant contribution in predicting the incidence of CRPS came from the intervention variable (OR 0.26, CI95% 0.08-0.85; P = 0.027)., Conclusions: The findings suggest that adding vitamin C 500 mg to the local anesthetic in Bier block significantly reduces the incidence of CRPS following distal radius fractures.

A broad spectrum of conditions including neuropathic pain, complex regional pain syndrome (CRPS) and fibromyalgia, have been implicated as causes of chronic pain. There is a need for new and effective treatments that patients can tolerate without significant adverse effects. One potential intervention is hyperbaric oxygen treatment (HBOT). The case reported here is unique in describing repeated HBOT in a patient who developed recurrent post-traumatic CRPS of the lower as well as the upper limbs. In the first event, two months after distortion and abruption of the external right ankle, the patient suffered leg pain, oedema formation, mild hyperaemia, limited mobility of the ankle and CRPS Type 1. In the second event, the same patient suffered fracture-dislocation of the distal radius 1.5 years after the first injury. After the plaster cast was removed the patient developed pain, warmth, colour changes, oedema formation and limited wrist mobility with CRPS Type 1. Pharmacological treatment as well as HBOT were used with significant improvement of functional outcome in both cases. Some studies suggest that patients with a history of CRPS are more likely to develop secondary CRPS compared to the rates reported in the literature among the general population. Patients with a history of CRPS should be counselled that they may be at risk for developing secondary CRPS if they undergo surgery or sustain trauma to another extremity., (Copyright: This article is the copyright of the authors who grant Diving and Hyperbaric Medicine a non-exclusive licence to publish the article in electronic and other forms.)

Complex regional pain syndrome (CRPS) is characterized by pain accompanied by symptoms including skin changes, sensory, motor, trophic changes and autonomic dysfunction. Anticonvulsants and antidepressants are commonly prescribed for neuropathic pain conditions; however, evidence is sparse whether these drugs are effective in reducing CRPS-related pain. As such, Pubmed was searched for studies published from January 1990 through March 2020; 13 studies were included in this review. Overall, evidence is considered insufficient for use of gabapentinoids for CRPS-related pain. However, three randomized controlled trials (RCTs) did find gabapentin to result in significant improvement in pain whereas one RCT reported use of amitriptyline to be equally as effective as gabapentin. Multiple case reports discussing the efficacy of pregabalin in pediatric CRPS patients, with relatively short duration of disease and underlying psychiatric illness, have been reported, but these findings need to be validated with RCTs.

Purpose of Review: Complex regional pain syndrome (CRPS) is a debilitating pain condition that often requires a multidisciplinary approach including medication, physical therapy, occupational therapy, psychological therapy, and interventional procedures to restore the patient's quality of life. This article reviews the interventional treatments for pain resulting from CRPS., Recent Findings: Sympathetic nerve blocks (stellate ganglion and lumbar sympathetic) are the first-line interventional treatment options for patients with CRPS of the upper and lower extremities, respectively. Fluoroscopic techniques for lumbar sympathetic blocks have not significantly changed throughout the years. However, both novel fluoroscopic and ultrasound approaches to stellate ganglion blockade have arisen. In addition, novel neuromodulation therapies to treat CRPS have been developed to include new waveforms with dorsal column stimulation and entirely new nerve targets such as dorsal root ganglion stimulation. This paper will review the latest interventional treatment options available for the treatment of CRPS.

Background: An unusual case involving a middle-aged male with a 9-year history of presumptive chronic regional pain syndrome (CRPS) and ulnar neuropathy was referred for failure in treatment. Methods: On presentation, the patient was requesting an amputation of his arm. However, work-up uncovered a periosteal extra-digital glomus tumor on the base of the small finger metacarpal. Results: Surgical excision of the lesion resulted in rapid resolution of his pain and normal hand function was ultimately restored. Conclusions: Glomus tumors account for up to 5% of all soft tissue tumors of the upper extremity, occurring most frequently within or adjacent to the nail bed. Time from onset of symptoms to correct diagnosis may not be established for many years, especially with atypical tumor locations. Although glomus tumors have been widely reported, atypical locations of these tumors should be included in the differential diagnosis for patients with unusual chronic pain or neuropathy. Furthermore, when evaluating a chronic pain patient, our findings support the opinion that assignment of the diagnosis of CRPS should only be a diagnosis of exclusion.