Search

Introduction: This case report presents an instance of an S-Series™ slim paddle lead fracturing during extraction, highlighting potential risks associated with the removal of this lead., Case Report: A 47-year-old male with complex regional pain syndrome type 2, unresponsive to pharmacotherapy, had undergone the implantation of two spinal cord stimulator (SCS) leads, an Octrode™ cylindrical and an S-series™ slim paddle, using the Epiducer™ system (St Jude Medical) 9 years earlier, with a subsequent intrathecal baclofen pump installed 1 year after SCS. Initially, these interventions stabilized the patient's pain symptoms. However, the diminishing effectiveness of SCS, coupled with a decrease in battery life and increased opioid consumption, necessitated recent surgical procedures. These included the removal and replacement of the implantable pulse generator (IPG) and leads to improve pain management and ensure MRI compatibility. During the removal of the S-series™ slim paddle type lead, complications arose, leading to the retention of an electrode fragment, which necessitated abandoning the replacement of both the IPG and lead. Post-surgical assessments revealed no new neurological impairments, and imaging studies confirmed the stable position of the retained fragment. The patient was discharged with a continued comprehensive pain management plan., Conclusion: This case highlights the challenges and risks of percutaneous removal of slim paddle type leads, emphasizing the need for careful procedural planning and consideration of surgical options to avoid complications. Further research is needed to evaluate the long-term durability and removal risks of various SCS lead types., (© 2024 World Institute of Pain.)

Background: Children under the age of 3 years have been diagnosed with complex regional pain syndrome (CRPS). They were found to be functionally disadvantaged and psychologically distressed in relation to children with other painful conditions., Case Presentation: An 18-month-old baby girl was referred to the pain clinic with a history of severe right lower limb pain that had begun 2 months earlier. The parents were unable to recall any trauma before the painful situation. Pain and allodynia were severe and extended from the toes to the gluteus area. She was low weight for her age (6700 g). The patient was on the maximum doses of gabapentin and amitriptyline accepted for her body weight and did not have the possibility to start rehabilitation due to severe pain and allodynia. After discussing the risks and potential benefits of a planned lumbar sympathetic block (LSB), the parents approved the interventional procedure. This is the first case report describing the LSB technique at such a young age., Method: A lumbar sympathetic block was carried on at the third lumbar vertebral level, fluoroscopy-guided, and under general anesthesia (GA) initiated with ketamine iv. A 4-cm needle was introduced using a tunneled vision approach in an oblique view at the L3 level until adequate depth was confirmed in the lateral position. Safety considerations were taken in relation to the radiation dose and all drugs injected with dose adjustment to her body weight. The block was successful (the skin temperature increased by 2.8 °C) and was uneventful. Pain and allodynia were completely alleviated in the recovery room. At the follow-up after 3 and 8 weeks, the parents reported an 80% improvement in pain and allodynia, a 70% improvement in sleep, a weight gain of 900 g, and that she had started rehabilitation., Conclusions: Lumbar sympathetic blocks can be considered at a very young age to treat CRPS if other non-invasive measures fail., (© 2024. The Author(s).)

Purpose: Pain, allodynia, and stiffness in complex regional pain syndrome (CRPS) greatly affects social, vocational, and community engagement. The aim of this study was to evaluate the effect of isolated median nerve releases on the outcome of CRPS 1 of the hand., Methods: In this prospective case series, people of any age diagnosed with and treated for CRPS 1 of the upper limb attending the author's practice were consecutively recruited. All were self-referrals dissatisfied with the treatment provided previously. Only patients who had been treated with nerve release to control their symptoms were included. Primary outcome measures were pain and Disabilities of the Arm, Shoulder, and Hand score. A secondary outcome was withdrawal from pain medication. Full resolution was defined as 0 pain, on a scale of 0-10, and total withdrawal from pain medication at the latest follow-up., Results: Between January 2018 and December 2022, 82 participants with CRPS 1 of the hand for an average of 20 months were evaluated. Eighty-five nerve releases were performed. As per protocol, carpal tunnel release was performed in all, and three patients also received an endoscopic pronator release. Minor procedures unrelated to the pain were carried out concomitantly in 17 patients. Significant improvements were observed in pain score (mean 8.9 ± 1.2 at baseline vs 0.6 ± 1.8 at 35 months) and in Disabilities of the Arm, Shoulder, and Hand score (82 ± 13 vs 13 ± 20) for the same period. Five patients (6%) were considered failures. In contrast, 65 patients (79%) had full resolution of their symptoms., Conclusions: This study demonstrates that a large percentage of patients diagnosed with and treated for CRPS type 1 can have full resolution of their symptoms with carpal tunnel release. Future research is needed to understand the pathophysiology and the failures., Type of Study/level of Evidence: Therapeutic II., Competing Interests: Conflicts of Interest No benefits in any form have been received or will be received related directly to this article., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

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.)

Intercostal neuralgia is characterized by neuropathic pain along the distribution of the intercostal nerve, which can cause debilitating pain and interfere with daily activities. The literature is extremely limited in assessing the use of neuromodulation to treat trauma-induced intercostal neuralgia. This case reports a 40-year-old patient who presented with decades of refractory, long-standing thoracic pain. The pain ranged from a four out of 10 to a nine out of 10 on the numeric rating scale (NRS). The patient failed pharmacologic therapy, physical therapy, chiropractic care, injection therapy, transcutaneous electrical nerve stimulation (TENS), and spinal cord stimulation (SCS). The patient underwent a 60-day peripheral nerve stimulation (PNS) trial, which temporarily relieved the pain until it was explanted. The patient subsequently underwent placement of a permanent PNS implant, which provided between 80-100% daily pain relief at a six-month follow-up. At the two-year follow-up, the patient continued to experience sustained pain relief, had weaned from opioid medications, and returned to all desired daily activities. This case suggests that minimally invasive PNS can effectively manage pain for patients with intercostal neuralgia who fail conservative measures. Further, to our knowledge, this two-year follow-up is the longest-reported outcome in the literature for using PNS for intercostal neuralgia after traumatic injury., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Gallacher et al.)

Silique development exerts significant impacts on crop yield. CRPs (Cysteine-rich peptides) can mediate cell-cell communication during plant reproduction and development. However, the functional characterization and regulatory mechanisms of CRPs in silique development remain unclear. In this study, we identified many CRP genes downstream of the CRP gene TPD1 (TAPETUM DETERMINANT1) during silique development using a microarray assay. The novel Arabidopsis thaliana pollen-borne CRPs, the PCP-Bs (for pollen coat protein B-class) gene AtPCP-Ba , along with TPD1 , are essential for silique development. The AtPCP-Ba was significantly down-regulated in tpd1 flower buds but up-regulated in OE-TPD1 flower buds and siliques. The silencing of AtPCP-Ba compromised the wider silique of OE-TPD1 plants and inhibited the morphology of OE-TPD1 siliques to the size observed in the wild type. A total of 258 CRPs were identified with the bioinformatic analysis in Arabidopsis , Brassica napus , Glycine max , Oryza sativa , Sorghum bicolor , and Zea mays . Based on the evolutionary tree classification, all CRP members can be categorized into five subgroups. Notably, 107 CRP genes were predicted to exhibit abundant expression in flowers and fruits. Most cysteine-rich peptides exhibited high expression levels in Arabidopsis and Brassica napus . These findings suggested the involvement of the CRP AtPCP-Ba in the TPD1 signaling pathway, thereby regulating silique development in Arabidopsis .

Visuomanual prism adaptation (PA), which consists of pointing to visual targets while wearing prisms that shift the visual field, is one of the oldest experimental paradigms used to investigate sensorimotor plasticity. Since the 2000's, a growing scientific interest emerged for the expansion of PA to cognitive functions in several sensory modalities. The present work focused on the aftereffects of PA within the auditory modality. Recent studies showed changes in mental representation of auditory frequencies and a shift of divided auditory attention following PA. Moreover, one study demonstrated benefits of PA in a patient suffering from tinnitus. According to these results, we tried to shed light on the following question: How could this be possible to modulate audition by inducing sensorimotor plasticity with glasses? Based on the literature, we suggest a bottom-up attentional mechanism involving cerebellar, parietal, and temporal structures to explain crossmodal aftereffects of PA. This review opens promising new avenues of research about aftereffects of PA in audition and its implication in the therapeutic field of auditory troubles., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We present on a patient with complex regional pain syndrome (CRPS) following ankle surgery. Pain was refractory to both conservative and surgical measures including neurotomies, ankle fusion, hardware removal, and spinal cord stimulation (SCS) trial. A dorsal root ganglion (DRG) stimulation trial with lead placements at L4, L5, and S1 provided significant pain and functional improvement. However, during the implantation, we were able to place only two DRG leads at L4 and L5 and not S1 due to difficulties with advancing the lead to the desired location. Nonetheless, the two DRG leads provided 90% pain relief and 75% functional improvement for 9 months. However, the patient experienced pain symptoms similar to that of pre-implant without a clear trigger after 9 months despite no DRG stimulator hardware malfunction or lead migration. A decision was made to re-try implanting the S1 DRG lead, which was successful and provided significant pain relief., Competing Interests: The authors have no competing interests to report in this work., (© 2024 Her and Churchill.)

Background: Available therapeutic options are currently limited by their modest efficacy. As a result, novel pharmacotherapeutic treatments with different mechanisms have recently attracted empirical attention. Magnesium, a divalent cation, is postulated to provide analgesic and anti-nociceptive effect through its action at the N-methyl-D-aspartate (NMDA) receptor., Objective: Considering the evidence surrounding magnesium's potential as a therapeutic modality for chronic pain, we conducted a narrative review on the evidence of magnesium's therapeutic effects in chronic pain., Methods: A review of the PubMed, and Google scholar databases was undertaken in May 2022 to identify completed studies that investigated the effectiveness of magnesium in the treatment of chronic pain from database inception to May 2022., Results: A total of 33 studies were included in the narrative review, out of which 26 were randomized controlled trials. Findings on available studies suggest that intravenous infusion of magnesium is an emerging and promising option that may alleviate pain in some clinical populations. Our narrative synthesis showed that evidence for intravenous magnesium is currently equivocal for a variety of chronic pain syndrome. Findings indicate that evidence for efficacy is poor or equivocal for: CRPS, neuropathic pain, chronic low back pain, and migraine prophylaxis. However, there is good evidence supporting the efficacy of intravenous magnesium for treating renal colic pain and pelvic pain related to endometriosis., Conclusion: Magnesium may be a promising pharmacologic solution for chronic pain. Future investigation is warranted on elucidating the neurobiological mechanisms of magnesium in attenuating pain signaling pathways., (Copyright © 1964–2024 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

This paper presents a case of a 35-year-old female patient diagnosed with Complex Regional Pain Syndrome (CRPS) type I and treated over a two-month period with a novel low-frequency sound-transduced focal pulsed stimulus. The patient received 21 treatments consisting of focally applied sound sweeps in the 15-100 Hz range. Outcome measures included the Visual Analogue Scale for pain, five physical assessment parameters, medication, and the Pain Catastrophizing Scale. A follow-up was conducted at six months. The results show that the patient's low-back pain level was substantially reduced after treatment and after six months. CRPS-related peripheral pain was strongly reduced but had some rebound after six months. The low-frequency sound-transduced focal pulsed stimulus shows potential as a non-invasive treatment for CRPS and deserves controlled clinical trials.

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).)

Introduction: Fluctuations of chronic pain levels are determined by a complex interplay of cognitive, emotional and perceptual variables. We introduce a pain tracking platform composed of wearable neurotechnology and a smartphone application to measure and predict chronic pain levels and its interplay with other dimensions of experience., Methods: Our method measures, dynamically and at home, pain strength, phenomenal and neural time series collected with an online tool and low-density EEG. Here we used data from a single participant who performed an attention task at home for a period of 20 days to investigate the role of attention to different bodily systems in chronic pain., Results: We show a relationship between emotions and pain strength while allocating attention to the heartbeat, the breathing, the affected or the unaffected limb. We found that pain was maximal when attending to the affected limb and decreased when the participant focused on his breathing or his heartbeat. These results provide interesting insights regarding the role of attention to interoceptive signals in chronic pain. We found power changes in the delta, theta, alpha and beta (but not in the gamma) band between the four attention conditions. However, there was no reliable association of these changes to pain intensity ratings. Theta power was higher when attention was directed to the unaffected limb compared to the others. Further, the pain ratings, when attending to unaffected limb, were associated with alpha and theta power band changes., Conclusion: Overall, we demonstrate that our neurophysiology and experience tracking platform can capture how body attention allocation alters the dynamics of subjective measures and its neural correlates. This research approach is proof of concept for the development of personalized clinical assessment tools and a testbed for behavioural, subjective and biomarkers characterization., Competing Interests: TAB is Co-founder and JS a part time associate at Human Experience Dynamics, Ltd. The methods of this paper are an example of joint work as a Lab in the University of Cambridge and as a spin off company (Human Experience Dynamics, Ltd). This work benefited from the developments done both by the Lab and Company. The other authors report no conflicts of interest in this work., (© 2024 Niedernhuber et al.)

Background: Complex regional pain syndrome (CRPS) is a disabling painful disorder caused by many different and poorly understood mechanisms. It often affects the distal limbs and usually happens as consequence of a trauma. Its severity can remarkably affect patients' quality of life. When this painful complication happens in a cancer patient, the impact may be exponential. To date, there is limited knowledge of the surrounding circumstances of CRPS cases in this population., Methods: We present two clinical cases of patients diagnosed with cancer-related pain presenting with symptoms and signs compatible with CRPS. In one case, CRPS was attributed to direct tumor nerve compression, and it responded successfully to an interventional pain procedure. The second case was associated with a Zoster infection in an immunocompromised cancer patient. Patient responded to multidisciplinary pain management strategies. Additionally, we conducted a literature review to investigate the coexistence of cancer pain and CRPS and suggest some pathophysiology mechanisms of action., Results and Discussion: Literature reviewed and potential pathophysiology mechanisms are simultaneously explored in terms of classification, etiopathology, evidence, challenges, and future scientific directions., Conclusion: Comorbid CRPS can impact negatively in cases of cancer pain by affecting their diagnosis and treatment. Further studies are necessary to elucidate how these two conditions present together and how they can be better addressed., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Thanaboriboon et al.)

In the human body, ascorbic acid (AA) is known for its potent antioxidant and reducing properties and also plays a vital role in supporting the growth of bones and cartilage. It has been used extensively in orthopedic surgery. Ongoing studies under the umbrella of ascorbic acid research investigate its impact on bone and tendon physiology, as well as its influence on joint replacement and postoperative pain. The majority of both laboratory and human studies link the usage of ascorbic acid to enhanced bone health and improved tendon healing. Recent literature suggest that ascorbic acid administration may have a positive impact on the outcome of orthopedic procedures. On the other hand, controversy exists regarding the efficacy of ascorbic acid in reducing the incidence of complex regional pain syndrome. In brief, the effectiveness of ascorbic acid in enhancing orthopedic procedure outcomes remains a subject of ongoing investigation. Although certain studies have hinted at the potential positive influence of ascorbic acid on these outcomes, further research is required to validate its effectiveness and ascertain the ideal dosage and method of administration for maximizing its anticipated advantages. To establish the efficacy of ascorbic acid in improving orthopedic procedure outcomes, rigorous human trials of high quality are imperative. The aim of this review was to provide an overview of ascorbic acid's utilization in orthopedic practices and to pinpoint prospective areas for future research., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Qamar et al.)

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).)

Patients who present to pain clinics with complex regional pain syndrome (CRPS) typically have debilitating pain, including hyperalgesia and allodynia, and additional substantial quality-of-life concerns related to the motor and autonomic-related symptoms of CRPS. Present treatments for CRPS such as neuropathic pain medications and sympathetic blocks are often unsatisfactory for managing symptoms. The present cases highlight the use of a 60-day percutaneous peripheral nerve stimulation (PNS) treatment for three patients with CRPS Type I affecting the foot. In all three patients, the tibial and common peroneal nerves were targeted separately at the popliteal fossa with two percutaneous leads each placed a remote distance (~1 cm) from the target nerve under ultrasound guidance. All three patients reported substantial pain relief and resolution of autonomic symptoms (e.g., swelling, edema, erythema), with sustained relief lasting 8-10 months in two patients, and 34 months (as of this writing) in the third patient. There were no medical complications. These three cases suggest that 60-day PNS is a safe and efficacious treatment for CRPS., Competing Interests: Claire A. Zurn and Nathan D. Crosby are co-inventors on patents related to the technology described in this work., (Copyright © 2024, Gutierrez et al.)

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.)

Complex regional pain syndrome (CRPS) is a debilitating painful state of an extremity that can develop after trauma. CRPS is diagnosed by the new International Association for the Study of Pain (IASP) diagnostic criteria for CRPS. The syndrome is characterized by continuing regional pain with abnormal sensory, motor, sudomotor, vasomotor, edema, and/or trophic signs. The clinical presentation of CRPS can be very heterogeneous because CRPS is a multi-mechanism syndrome. Therefore, mechanism-based subgroups have been suggested to personalize treatment for CRPS. Additionally, the presentation of symptom pain may also be able to identify different subgroups of CRPS. In this review, the types of pain recognized by the IASP-nociceptive, neuropathic, and nociplastic pain-will be discussed as possible subgroups for CRPS. Each pain type should be identified in CRPS patients, with a thorough history taking, physical examination, and diagnostic tests or (novel) biomarkers to optimize treatment effectiveness. Over the course of the syndrome, patients with CRPS probably experience more than one distinct pain type. Therefore, pain specialists should be alert to not only adjust their treatment if underlying pathophysiologic mechanisms tend to change but also to personalize the treatment of the associated type of pain in the CRPS patient., Competing Interests: Prof. Dr. FJPM Huygen reports personal fees for educational work and grants from ABBOTT, Saluda, and Boston Scientific outside the submitted work. Prof. Dr. Frank JPM Huygen also has patents P121304EP00 and P121304NL00 pending to DRG stimulation for spasticity. The authors report no other conflicts of interest in this work., (© 2023 Mangnus et al.)

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.)

Complex regional pain syndrome (CRPS) is a chronic neurologic painful disorder usually present after a traumatic insult. It is divided into two subtypes based on the absence of a significant nerve injury: type 1 or dystrophy and type 2 or causalgia. The exact mechanism still needs to be fully understood. The management of CRPS requires a multidisciplinary team approach with a rehabilitation program and physical and occupational therapies. We present a case report of a 22-year-old Saudi female with no medical or surgical history who presented to the clinic with severe pain, swelling, and discoloration in the left lower limb associated with unusual symptoms of non-epileptic convulsion attack and short-term memory loss for three years that increased in intensity. There was marked swelling and discoloration of the left lower limb, which was more significant at the foot, and the limb was tender and warm to the touch and allodynia. A slight touch to the limb led to a whole-body non-epileptic convulsion lasting for less than 30 seconds and loss of short-term memory and consciousness following the convulsion attack. A multidisciplinary team primarily managed the patient. In this case, the rarity and refractory to medical management emphasize the importance of understanding the different therapeutic modalities in managing this syndrome. However, more studies are warranted to understand the exact cause, pathogenesis, and available treatment options., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Alghamdi et al.)

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).)

This case report describes the dramatic clinical response of refractory chronic complex regional pain syndrome to combined immunomodulatory treatment. Ketamine and rapamycin markedly minimized pain historically associated with suicidal behavior, increased baseline activity, and allowed for a reduction in palliative polypharmacy. The piecewise mechanism of action is unclear given multiple postulated targets, such as microglia, astroglia, T-regulatory cells, B-regulatory cells, or neurons. Relevant laboratory and genetic information may allow the application of this treatment to other affected individuals., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sharma et al.)

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.

Objectives: The objective of this study was to assess the outcomes of the use of electrodiagnosis in the diagnosis and management of discrete nerve injuries in patients with complex regional pain syndrome (CRPS)., Design: This study is a secondary retrospective cohort analysis of patients diagnosed with CRPS from a single outpatient physical medicine and rehabilitation clinic and included all patients who had abnormal electrodiagnostic findings, in addition to CRPS., Results: Sixty patients of 248 diagnosed with CRPS underwent electrodiagnosis, 41 of whom had abnormal electrodiagnostic findings indicating a discrete nerve injury. Only 51% of the 41 referrals had indicated the suspicion of a nerve injury. Nearly all patients had undergone physiotherapy. Forty-one percent responded to treatment with oral prednisone alone, 54% had a functional improvement after a combination of treatments including corticosteroids, and 5% improved with treatments that did not involve corticosteroids. Surgical interventions for nerve injuries were required for 34% of patients in the cohort. All surgeries involved the median or ulnar nerve, with the exception of one fibular nerve. After treatment, 39 of 41 patients had functional recoveries or better., Conclusions: Electrodiagnosis can inform diagnosis of nerve injury and direct intervention including the need for surgical intervention. Electrodiagnosis should be considered for patients with initial signs of concomitant discrete nerve injury or with CRPS who are not responding to treatments because a nerve injury may be underlying., What is Known Complex Regional Pain Syndrome (CRPS) is a poorly understood pain condition. CRPS has been divided into two subtypes, the second subtype involves a discrete nerve injury with pain that extends beyond the territory of the nerve injury., What is New We observed that nerve injuries that may require surgical intervention are diagnosed just over half of the time upon initial assessment in patients with suspected CRPS. We observed that nerve injuries frequently required specifically directed interventions in place of or in conjunction with CRPS treatments. We suggest that electrodiagnosis is an important part of the triage protocol for CRPS II to reveal discrete nerve injuries that may be hidden. We recommend that electrodiagnosis be considered for patients with initial signs of concomitant discrete nerve injury or for CRPS patients who do not improve with medical therapies., Competing Interests: No potential conflict of interest was reported by the authors., (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Complex regional pain syndrome (CRPS) is a systemic or regional pain pathology associated with the nondermatomal or dermatomal distribution of excruciating intolerable pain, which might be triggered by an insignificant or weak stimulus or sometimes without any. Its symptoms encompass neurological, musculoskeletal, dermatological, and vascular realms. It is usually preceded by an episode of nerve injury or intervention set in numerous circumstances ranging from trauma to surgeries to chronic diseases. CRPS has been shrouded in a veil of mystery  and was called a psychological  phenomenon without any proper organic basis when it was described by Ambroise Pare initially. This led to disproportionately fewer research investments into this disease. Given the great advancement of diagnostic modalities since its inception, researchers and physicians have been trying to identify the physiological basis for it and have succeeded. Numerous pathophysiological pathways have been involved in this disease, but all of them point toward the possibility of improper pain processing at various levels of the pain pathway along with brain plasticity leading to aberrant neuronal circuitry between different segments of the sensory cortex, basal ganglia, prefrontal cortex, and insula. This paper explores the various studies done to evaluate the role of different imaging modalities, ranging from three-phase bone scintigraphy (TPBS) to diffusion traction imaging (DTI)., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Tangella et al.)

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.)

The aim of the present study was to compare the analgesic effect of motor cortex stimulation using high-frequency repetitive transcranial magnetic stimulation or transcranial direct current stimulation and transcutaneous spinal direct current stimulation in patients with complex regional pain syndrome. Thirty-three patients with complex regional pain syndrome were randomized to one of the three treatment groups (repetitive transcranial magnetic stimulation, n = 11; transcranial direct current stimulation, n = 10; transcutaneous spinal direct current stimulation, n = 12) and received a series of 12 sessions of stimulation for 3 weeks (induction phase) and 11 sessions for 4 months (maintenance therapy). The primary end-point was the mean pain intensity assessed weekly with a visual numerical scale during the month prior to treatment (baseline), the 5-month stimulation period and 1 month after the treatment. The weekly visual numerical scale pain score was significantly reduced at all time points compared to baseline in the transcutaneous spinal direct current stimulation group, at the last two time points in the repetitive transcranial magnetic stimulation group (end of the 5-month stimulation period and 1 month later), but at no time point in the transcranial direct current stimulation group. A significant pain relief was observed at the end of induction phase using transcutaneous spinal direct current stimulation compared to repetitive transcranial magnetic stimulation ( P = 0.008) and to transcranial direct current stimulation ( P = 0.003). In this trial, transcutaneous spinal direct current stimulation was more efficient to relieve pain in patients with complex regional pain syndrome compared to motor cortex stimulation techniques (repetitive transcranial magnetic stimulation, transcranial direct current stimulation). This efficacy was found during the induction phase and was maintained thereafter. This study warrants further investigation to confirm the potentiality of transcutaneous spinal direct current stimulation as a therapeutic option in complex regional pain syndrome., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Outcomes after spinal cord stimulator (SCS) placement are affected by psychologic comorbidities. It is part of routine practice to do psychologic assessments prior to SCS trials to assess for the presence of maladaptive behavioral patterns. However, few studies have sought to quantify the effect of psychiatric comorbidities on complications, reoperation, and readmission rates. The purpose of this study was to assess the association of psychiatric comorbidities with postprocedural outcomes after SCS implantation., Materials and Methods: Inclusion criteria included SCS placement between 2015 and 2020 (percutaneous approach or an open laminectomy-based approach) using Healthcare Corporation of America National Database. Data on psychiatric comorbidities present at the time of SCS implantation surgery were collected. Outcomes of interest included complication rates (defined as lead migration, fracture, malfunction, battery failure, postoperative pain, infection, dural puncture, or neurological injury), reoperation rates (defined as either revision or explant [ie, removal]), and readmission rates within 30-day and 1-year time after SCS implantation. We measured the association between psychiatric comorbidities and outcomes using multivariable regression and reported odds ratio (OR) and respective 95% confidence intervals., Results: A total of 12,751 cases were included. The most common psychiatric comorbidities were major depressive disorder (16.1%) and anxiety disorder (13.4%). In unadjusted univariate analysis, patients with any psychiatric comorbidity had heightened rates of any complication (27.1% vs 19.4%), infection (5.9% vs 1.9%), lead displacement (2.2% vs 1.3%), surgical pain (2.1% vs 1.2%), explant (14.7% vs 8.8%), and readmission rates at one year (54.2% vs 33.8%) (all p < 0.001). In multivariable logistic regression, with each additional psychiatric comorbidity, a patient had increased odds of experiencing any complication (OR = 1.5, 95% CI = 1.36-1.57, p < 0.001), requiring a reoperation (OR = 1.5, 95% CI = 1.37-1.6, p < 0.001), and requiring readmission (OR = 1.7, 99% CI = 1.6-1.8, p < 0.001)., Conclusions: The presence of psychiatric comorbidities was found to be associated with postoperative complication rates, reoperation, and readmission rates after SCS placement. Furthermore, each consecutive increase in psychiatric comorbidity burden was associated with increased odds of complications, reoperation, and readmission. Future studies might consider examining the role of presurgical mental health screening (ie, patient selection, psychologic testing) and treatment in optimizing outcomes for patients with psychiatric comorbidities., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to evaluate discrepancies in prescription trends for analgesic medications in complex regional pain syndrome (CRPS) patients based on recommendations in the literature., Design: We conducted a retrospective case-control study., Subjects: A total of 2510 CRPS patients and 2510 demographic-matched controls participated in this study., Methods: The SlicerDicer feature in Epic was used to find patients diagnosed with CRPS I or II between January 2010 and November 2022. An equal number of age-, gender-, and race-matched controls without a CRPS diagnosis were retracted from Epic. General and CRPS-associated prescription frequencies for the following classes were retrieved for both cases and controls: benzodiazepines, bisphosphonates, calcitonin, capsaicin, neuropathic pain medications, NSAIDs, opioids, and steroids., Results: A total of 740 (29%) CRPS patients and 425 (17%) controls were prescribed benzodiazepines (95% CI 0.1-0.15), 154 (6.1%) CRPS patients and 52 (2.1%) controls were prescribed capsaicin (95% CI 0.03-0.05), 1837 (73%) CRPS patients and 927 (37%) controls were prescribed neuropathic pain medications (95% CI 0.05-0.34), 1769 (70%) CRPS patients and 1217 (48%) controls were prescribed opioids (95% CI 0.19-0.25), 1095 (44%) CRPS patients and 1217 (48%) controls were prescribed steroids (95% CI 0.08-0.14), and 1638 (65%) CRPS patients and 1765 (70%) controls were prescribed NSAIDs (95% CI -0.08-0.02), p < 0.001 for all classes. With CRPS-associated prescriptions, (95% CI 0.05-0.16, p < 0.001) more CRPS patients were prescribed opioids (N = 398, 59%) than controls (N = 327, 49%)., Conclusions: CRPS is difficult to treat with significant variance in suggested treatment modalities. Based on the results of our study, there is a divergence between some published recommendations and actual practice.

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.

Purpose: Complex regional pain syndrome (CRPS) is a multi-mechanism disease, with an exaggerated inflammatory response as an important underlying mechanism. Auto-inflammation can theoretically be combated by anti-inflammatories, such as TNF-α inhibitors. This study's aim was to assess the effectiveness of intravenous infliximab, a TNF-α inhibitor, in patients with CRPS., Patients and Methods: CRPS patients treated with infliximab between January 2015 and January 2022 were approached to participate in this retrospective study. Medical records were screened for age, gender, medical history, CRPS duration, and CRPS severity score. Additionally, treatment effect, dose and duration, and side effects were extracted from medical records. Patients who still receive infliximab completed a short global perceived effect survey., Results: Eighteen patients received infliximab, and all but two gave consent. Trial treatment with three sessions of 5 mg/kg intravenous infliximab was completed in 15 patients (93.7%). Eleven patients (73.3%) were categorized as responders with a positive treatment effect. Treatment was continued in nine patients, and seven patients are currently treated. Infliximab dose is 5 mg/kg, and frequency is every four to six weeks. Seven patients completed a global perceived effect survey. All patients reported improvement (median 2, IQR 1-2) and treatment satisfaction (median 1, IQR 1-2). One patient described side effects such as itching and rash., Conclusion: Infliximab proved effective in 11 out of 15 CRPS patients. Seven patients are still being treated. Further research is needed on the role of infliximab in the treatment of CRPS and possible predictors of response to treatment., Competing Interests: Frank J.P.M. Huygen reports personal fees from Abbott; grants and personal fees from Saluda; and personal fees from Boston Scientific, Grunenthal, and Pfizer outside the submitted work. Corinne van den Berg, Maaike Dirckx and Jitske Tiemensma report no conflicts of interest in this work., (© 2023 van den Berg et al.)

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.)

Complex regional pain syndrome (CRPS) is a complex condition characterized by chronic pain and various sensory, motor, and autonomic symptoms. It involves a complex interplay of mechanisms in the nervous system, including neuroinflammation, sensitization of pain pathways, and dysfunction of the sympathetic nervous system. Antioxidants may play a role in CRPS by helping to counteract oxidative stress, which is an imbalance between the production of reactive oxygen species (ROS) and the body's antioxidant defences. CRPS involves inflammation and tissue damage, which can lead to increased ROS production and oxidative stress. Our paper represents a preliminary study on various commercially available natural-based products regarding their antioxidant effect. Several natural products with antioxidant properties, such as vitamins C and E, polyphenols, flavonoids, and botanical extracts, have shown promise in preclinical studies for their potential to alleviate pain and reduce inflammation associated with CRPS. The potential use of natural-based products with antioxidant effects for mitigating CRPS symptoms is still an area of ongoing research and investigation, but nonetheless it holds promise., Competing Interests: None to declare, (Copyright © 2023, Medical University Publishing House Craiova.)

Purpose: The clinical features of classic carpal tunnel syndrome are well known. However, some patients who may respond equally well to carpal tunnel release (CTR) display atypical signs and symptoms. The chief differential features are allodynia (painful dysesthesias), lack of finger flexion, and, on examination, pain on passive finger flexion. The goal of the study was to present the clinical features, increase awareness, facilitate accurate diagnosis, and report the outcomes after surgery., Methods: Thirty-five hands, from 22 patients with the main features of allodynia and lack of full finger flexion, were gathered in the period 2014-2021. The other common complaints included sleeping disturbances (20 patients), hand swelling (31 hands), and shoulder pain on the same side as the hand problem with limited range of motion (30 sides). The Tinel or Phalen signs were obscured by the pain. However, pain with passive flexion of the fingers was universally present. All the patients were treated with carpal tunnel release through a mini-incision approach: four patients had a trigger finger, which was treated concomitantly in six hands, and one patient underwent contralateral CTR for carpal tunnel syndrome with a more standard presentation., Results: At a minimum of 6 months of follow-up (mean, 22 months; range, 6-60 months), the pain decreased by 7.5 ± 1.9 points on the Numerical Rating Scale, which ranges from 0 to 10. The pulp-to-palm distance improved from 3.7 to 0.3 cm. The mean Disabilities of the Arm, Shoulder, and Hand score decreased from 67 to 20. The mean Single-Assessment Numeric Evaluation score for the whole group was 9.7 ± 0.6., Conclusions: Hand allodynia and lack of finger flexion may be indications of median neuropathy in the carpal canal, which responds to CTR. Awareness of this condition is important because the uncharacteristic clinical presentation may not be considered an indication for surgery that can be beneficial., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2023. Published by Elsevier Inc.)

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).)

Complex regional pain syndrome (CRPS) is a debilitating condition characterized by autonomic and inflammatory features, often caused by fractures, surgeries, or other injuries. Multimodal treatment is utilized, which often includes neuropathic medications and physical therapy. We had a case of a 24-year-old man who was diagnosed with CRPS II following an open reduction and internal fixation of a trimalleolar fracture. Significant improvement of edema, pain, and function was achieved with early initiation of gabapentin, nortriptyline, and physical therapy. In this case report, we discuss the therapeutic challenges regarding his recovery and review the literature on the utility of medications and interventional methods in treating CRPS II. We note that early treatment response may be an important prognostic indicator for the progression of CRPS II and additional studies targeting interventions for the specific type and clinical stage of CRPS are needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Caradonna et al.)

Purpose: To assess and compare the healthcare costs, time to fitness for work (TFW) between chronic complex regional pain syndrome (CRPS) and non-CRPS; and identify factors associated with these outcomes in a comparative longitudinal study., Patients and Methods: 148 patients with chronic CRPS of the hand and 273 patients with chronic hand impairments but without CRPS (non-CRPS) were admitted at a Swiss rehabilitation clinic between 2007 and 2016. Healthcare costs and TFW were retrieved from insurance data over 5 years after the accident. Socio-demographic factors, biopsychosocial complexity measured by means of the INTERMED questionnaire, pain intensity and DASH disability scores were collected during rehabilitation. Generalized estimation equations and Cox proportional-hazards models were used to identify factors associated with outcomes., Results: Healthcare costs were increased by 20% for the CRPS versus non-CRPS group (coefficient = 1.20, 95% CI = 1.08-1.35, p<0.001). The median TFW was longer for CRPS than non-CRPS patients (816 vs 672 days, p = 0.02). After adjusting for covariates, TFW did not differ between the two groups (hazard ratio = 0.94, 95% CI = 0.73-1.21, p=0.61). For CRPS patients, higher healthcare costs were associated with severe or moderate initial injury, high INTERMED or DASH disability scores. Longer TFW were associated with severe initial injury, low educational level, no work contract, and high INTERMED or DASH disability scores., Conclusion: Overall, the healthcare costs were higher for CRPS than non-CRPS patients, but the TFW was comparable. We demonstrated also the significant associations of disability and biopsychosocial factors with the healthcare costs and TFW in CRPS patients., Competing Interests: The authors report no conflicts of interest., (© 2023 Duong et al.)

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.)