Early versus persistent Complex Regional Pain Syndrome: Is there a difference in patient reported outcomes following rehabilitation?

BACKGROUND: Expert consensus asserts that early treatment of Complex Regional Pain Syndrome (CRPS) leads to better outcomes. Yet no evidence supports this assumption regarding the recognized gold standard of multidisciplinary functional rehabilitation. To address this, we aimed to establish if there is a difference in outcomes between early CRPS (<1 year symptom duration) and persistent CRPS (= >1 year symptom duration) following rehabilitation and whether any gains are maintained at three months. METHOD: Secondary analysis was conducted on previously collected clinical Patient Reported Outcome Measures (PROMS) data from 218 patients attending a residential multidisciplinary rehabilitation programme. Datasets were categorized into early CRPS (n = 40) or persistent CRPS (n = 178) dependent on symptom duration. Function, pain, self-efficacy, kinesiophobia and psychological health domains were compared using repeated measures analysis of covariance for a two group design for group difference post rehabilitation and at three month follow-up. RESULTS: Post-rehabilitation, both groups improved in pain, function, kinesiophobia, psychological health and self-efficacy. At three months, the persistent CRPS group maintained improvements in pain and function. This was not achieved in early CRPS. CONCLUSION: This exploratory study is the first to empirically test the assumption that those with early CRPS have better outcomes following rehabilitation. Our clinical data challenges this, as both early and persistent CRPS groups improved following rehabilitation. Findings indicate that rehabilitation benefits those with CRPS, regardless of symptom duration. However, unlike early CRPS, those with persistent CRPS sustain gains at follow-up. Further prospective exploration is warranted. SIGNIFICANCE: Expert consensus recommends early treatment for Complex Regional Pain Syndrome, yet there is little empirical evidence to support this. Our findings are the first to challenge this assumption by revealing no difference in outcomes between early and persistent CRPS post-rehabilitation. However, those with persistent CRPS maintain gains after three months, unlike people with early CRPS (symptoms < one year). These findings are relevant to clinical practice as they challenge established assumptions, suggesting a focus on improving early CRPS follow-up outcomes.

Access to Chronic Pain Services for Adults from Minority Ethnic Groups in the United Kingdom (UK): a Scoping Review.

BACKGROUND: Chronic pain services in the UK are required to provide services which meet the diverse needs of patients, but little is known about the access and use of these services by minority ethnic groups. OBJECTIVE: To assess the available evidence regarding the ethnic profile of adults who access secondary and tertiary chronic pain services in the UK. METHODS: A scoping review was conducted (August 2021-October 2021), comprising comprehensive literature searches using Embase, Medline and CINAHL databases and the grey literature. Studies were included if they reported on (i) access to chronic pain services in secondary and/or tertiary care in the UK, (ii) adults and (iii) stated the ethnicity of the involved participants. Studies were included if published between 2004 and 2021, as demographic data during this period would be broadly representative of the UK population, as per the 2021 UK census. A descriptive synthesis of the extracted data was performed. RESULTS: The search yielded 124 records after duplicates were removed. Following title and abstract screening, 44 full texts were screened, ten of which were included in the review. CONCLUSIONS: This is the first review to explore access to chronic pain services for adults from minority ethnic groups in the UK. Given the limited number of studies that met the inclusion criteria, the review highlights the need for routine collection of ethnicity data using consistent ethnic categories within UK chronic pain services and increased involvement of minority ethnic groups within chronic pain research. Findings should inform future research that aims to improve access to UK chronic pain services for adults from minority ethnic groups.

Global series: Complex regional pain syndrome: abstracts from the International Association for the Study of Pain complex regional pain syndrome SIG virtual symposia 2021.

The aim of this IASP complex regional pain syndrome (CRPS) SIG Global Series 2021 was to bring together clinicians including those from developing countries to better understand the clinical presentation of complex regional pain syndrome in countries with less well-published patient populations. The purpose was to learn from each other about the range of treatments, successful outcomes, and challenges experienced. These meeting proceedings comprise abstracts from nine countries that span 4 continents and are summaries of online presentations delivered by speakers representing these countries over the course of 2 symposia. The symposia were attended by a global audience of approximately 360 people. Patients with CRPS were described and treated by clinicians from countries across Asia (Pakistan, Jordan, South Korea, Taiwan, and Singapore), South America (Brazil and Peru), Africa (South Africa), and Europe (Norway). This reflects that CRPS exists across borders, ethnicities, and cultures. These proceedings provide a broader perspective within the international pain community about how we can better understand and treat CRPS across the globe.

Photochemistry of pyruvic acid is governed by photo-induced intermolecular electron transfer through hydrogen bonds.

Despite more than 85 years of research, the mechanism behind the photodecarboxylation of pyruvic acid remains elusive. Most studies focused on the gas and liquid phase of diluted solutions of pyruvic acid to understand the impact of sun light on the degradation of this molecule in the atmosphere. By analyzing concentrated supercooled solutions at 77 K, we demonstrate that instead of decarboxylating, the pyruvic acid molecule plays the role of electron donor and transfers an electron to an acceptor molecule that subsequently degrades to form CO2. We show that this electron transfer occurs via hydrogen bonding and that in aqueous solutions of pyruvic acid, the hydrated form is the electron acceptor. These findings demonstrate that photo-induced electron transfer via hydrogen bonding can occur between two simple carboxylic acids and that this mechanism governs the photochemistry of pyruvic acid, providing unexplored alternative pathways for the decarboxylation of photo-inactive molecules.

Labile Photo-Induced Free Radical in α-Ketoglutaric Acid: a Universal Endogenous Polarizing Agent for In†Vivo Hyperpolarized 13 C Magnetic Resonance.

Hyperpolarized (HP) 13 C magnetic resonance enables non-invasive probing of metabolism in vivo. To date, only 13 C-molecules hyperpolarized with persistent trityl radicals have been injected in humans. We show here that the free radical photo-induced in alpha-ketoglutaric acid (α-KG) can be used to hyperpolarize photo-inactive 13 C-molecules such as [1-13 C]lactate. α-KG is an endogenous molecule with an exceptionally high radical yield under photo-irradiation, up to 50 %, and its breakdown product, succinic acid, is also endogenous. This radical precursor therefore exhibits an excellent safety profile for translation to human studies. The labile nature of the radical means that no filtration is required prior to injection while also offering the opportunity to extend the 13 C relaxation time in frozen HP 13 C-molecules for storage and transport. The potential for in vivo metabolic studies is demonstrated in the rat liver following the injection of a physiological dose of HP [1-13 C]lactate.

Labile Photo-Induced Free Radical in α-Ketoglutaric Acid: a Universal Endogenous Polarizing Agent for In†Vivo Hyperpolarized 13C Magnetic Resonance.

Hyperpolarized (HP) 13C magnetic resonance enables non-invasive probing of metabolism in vivo. To date, only 13C-molecules hyperpolarized with persistent trityl radicals have been injected in humans. We show here that the free radical photo-induced in alpha-ketoglutaric acid (α-KG) can be used to hyperpolarize photo-inactive 13C-molecules such as [1-13C]lactate. α-KG is an endogenous molecule with an exceptionally high radical yield under photo-irradiation, up to 50 %, and its breakdown product, succinic acid, is also endogenous. This radical precursor therefore exhibits an excellent safety profile for translation to human studies. The labile nature of the radical means that no filtration is required prior to injection while also offering the opportunity to extend the 13C relaxation time in frozen HP 13C-molecules for storage and transport. The potential for in vivo metabolic studies is demonstrated in the rat liver following the injection of a physiological dose of HP [1-13C]lactate.

Pain Assessment for Individuals with Advanced Dementia in Care Homes: A Systematic Review.

Pain is prevalent in older people, especially in those with advanced dementia who have communication impairments. Although pain is recognised to be present in this population, it is often under-assessed and ineffectively managed. The assessment of pain in advanced dementia is extremely challenging and complex, particularly in institutional settings such as care homes. This study systematically reviews the literature to examine and characterise the evidence for the use of pain assessment tools in care homes with individuals living with advanced dementia. Relevant publications were sourced from electronic bibliometric medical databases including AMED, CINAHL Plus, Medline, PsycINFO, EMBASE, TRIP Pro, Google Scholar, and HINARI. The database search was supplemented by screening citations and reference lists, in addition to a grey literature searches. The search identified 2221 studies, among which 26 were included in the review. The majority of the studies were observational, which created a rich source of data to create four major themes. The findings were informed and shaped by working with key stakeholders to develop a conceptual model that can contribute to developing evidence-based practice. This highlights the importance of a comprehensive, multi-disciplinary approach to pain assessment in this population, which is beyond the use of tools.

Visual illusions modulate body perception disturbance and pain in Complex Regional Pain Syndrome: A randomized trial.

BACKGROUND: Effective treatment of longstanding Complex Regional Pain Syndrome (CRPS) is a challenge, as causal mechanisms remain elusive. People with CRPS frequently report distorted subjective perceptions of their affected limb. Evidence of pain reduction when the affected limb is visually altered in size suggests that visual illusions used to target central processing could restore coherence of this disrupted limb representation. We hypothesized that using virtual reality that alters hand image to match the patient's desired hand appearance would improve body perception disturbance and pain. Also, repeated exposure would maintain any therapeutic effect. METHODS: A blinded randomized controlled trial of 45 participants with refractory upper-limb CRPS and body perception disturbance (BPD) viewed a digital image of their affected hand for 1 min. The image was digitally altered according to the patient's description of how they desired their hand to look in the experimental group and unaltered in the control group. BPD and pain were measured pre- and post-intervention. A subgroup was followed up 2 weeks after a course of repeated interventions. RESULTS: BPD (mean-6, ±SD 7.9, p = 0.036, effect size [ES] = 0.6) and pain intensity (mean-0.43, ±SD 1.3, p = 0.047, ES = 0.5) reduced in 23 participants after single exposure compared to controls (n = 22). At follow-up, the subgroup (experimental n = 21; control n = 18) showed sustained pain reduction only (p = 0.037, ±SD 1.9, ES = 0.7), with an overall 1.2 decrease on an 11-point scale. CONCLUSIONS: Visually changing the CRPS hand to a desired appearance modulates BPD and pain suggesting therapeutic potential for those with refractory CRPS. Further research to optimize this therapeutic effect is required. SIGNIFICANCE: Visual bodily illusions that change the shape and appearance of the painful CRPS hand to that desired by the patient result in a rapid amelioration of pain and body perception disturbance in people with longstanding CRPS. These findings highlight the future potential of this drug-free approach in the treatment of refractory CRPS.

Mechanistic insight into novel sulfoxide containing SABRE polarisation transfer catalysts.

Signal Amplification By Reversible Exchange (SABRE) is a hyperpolarisation technique that commonly uses [Ir(H)2(carbene)(substrate)3]Cl complexes to catalytically transfer magnetisation from para-hydrogen derived hydride ligands to coordinated substrates. Here, we explore the reactivity of a novel class of such catalysts based on sulfoxide containing [IrCl(H)2(carbene)(DMSO)2], which are involved in the hyperpolarisation of pyruvate using SABRE. We probe the reactivity of this species by NMR and DFT and upon reaction with sodium pyruvate establish the formation of two isomers of [Ir(H)2(η2-pyruvate)(DMSO)(IMes)]. Studies with related disodium oxalate yield [Ir2(H)4(IMes)2(DMSO)2(η2-κ2-Oxalate)] that is characterised by NMR and X-ray diffraction.

Body Perception Disturbance and Pain Reduction in Longstanding Complex Regional Pain Syndrome Following a Multidisciplinary Rehabilitation Program.

OBJECTIVE: Clinical guidelines for the treatment of complex regional pain syndrome recommend multidisciplinary rehabilitation, yet limited evidence exists to support the effectiveness of this approach. Body perception disturbance, a common and debilitating feature of complex regional pain syndrome, is recommended by guidelines as important to treat. However, no study has yet explored whether disturbances change in response to multidisciplinary rehabilitation. We aimed to determine whether there is a change in body perception disturbance and pain following a two-week multidisciplinary rehabilitation program for complex regional pain syndrome. METHODS: Retrospective clinical data from complex regional pain syndrome patients who completed the program between September 2014 and December 2016 were extracted and anonymized. Data collected pre- and post rehabilitation comprising the Bath Body Perception Disturbance scale and a pain intensity numerical rating scale were analyzed. RESULTS: Thirty complete data sets were analyzed from a sample of 50 consecutive patient records. After the program, there was a significant reduction in body perception disturbance (P < 0.0001), strength of negative emotional feelings (P < 0.0001), and pain (P = 0.0038). There was a significant correlation between a change in disturbance and pain (r = 0.44, P = 0.024). No relationship was found between the duration of symptoms and changes in disturbance (r = 0.04, P = 0.82). CONCLUSIONS: This study provides evidence that both body perception disturbance and pain reduce after rehabilitation. Findings suggest that targeting these disturbances may be important in reducing pain and may be a potentially useful measure for recovery. Controlled trials are required to confirm the effectiveness of rehabilitation and determine what factors are responsible for these reductions.

Extending the Scope of 19F Hyperpolarization through Signal Amplification by Reversible Exchange in MRI and NMR Spectroscopy.

Fluorinated ligands have a variety of uses in chemistry and industry, but it is their medical applications as 18F-labelled positron emission tomography (PET) tracers where they are most visible. In this work, we illustrate the potential of using 19F-containing ligands as future magnetic resonance imaging (MRI) contrast agents and as probes in magnetic resonance spectroscopy studies by significantly increasing their magnetic resonance detectability through the signal amplification by reversible exchange (SABRE) hyperpolarization method. We achieve 19F SABRE polarization in a wide range of molecules, including those essential to medication, and analyze how their steric bulk, the substrate loading, polarization transfer field, pH, and rate of ligand exchange impact the efficiency of SABRE. We conclude by presenting 19F MRI results in phantoms, which demonstrate that many of these agents show great promise as future 19F MRI contrast agents for diagnostic investigations.

Heart age differentials and general cardiovascular risk profiles for persons with varying disabilities: NHANES 2001-2010.

BACKGROUND: Persons with disabilities are at risk for secondary conditions, including allostatic load contributing to cardiovascular disease. The General Cardiovascular Risk Profile (GCRP) estimates cardiovascular disease risk for individuals. The GCRP variables are present in the National Health and Nutrition Examination Survey (NHANES) for the Healthy People 2010 decade. OBJECTIVE/HYPOTHESIS: The objective of this study was to compare persons with varying disabilities versus persons without disabilities on GCRP cardiovascular disease risk estimates across the Healthy People 2010 decade. METHODS: Weighted cross-sectional one-way Analyses of Variance (ANOVA) and non-parametric Kruskal-Wallis analyses compared persons with each of eight disability types versus persons without disabilities for point estimate GCRP heart vascular age differential and Cox regression model ten-year risk estimate in each NHANES survey year for 2001-2010. RESULTS: Persons with mobility or vision disabilities had significantly (p < .025) greater ten-year percent risks for cardiovascular disease and negative heart vascular age differentials (with respect to actual age, therefore "older" hearts) than persons without disabilities. The GCRP dual models conflict for certain disabilities (e.g., hearing, physical/mental/emotional) but are consistently reliable measures of GCRP for persons with mobility limitations and vision disabilities. CONCLUSIONS: With higher CVD risk among persons with disabilities, there is a clear need for increased interventions to benefit the health of persons with disabilities. The GCRP represents a valuable, simple measurement that uses routinely collected examination data. Physicians and nurses can use the GCRP to make immediate CVD assessments and to provide point-of-contact counseling to patients with and without disabilities.

Could relatedness help explain why individuals lead in bottlenose dolphin groups?

In many species, particular individuals consistently lead group travel. While benefits to followers often are relatively obvious, including access to resources, benefits to leaders are often less obvious. This is especially true for species that feed on patchy mobile resources where all group members may locate prey simultaneously and food intake likely decreases with increasing group size. Leaders in highly complex habitats, however, could provide access to foraging resources for less informed relatives, thereby gaining indirect benefits by helping kin. Recently, leadership has been documented in a population of bottlenose dolphins (Tursiops truncatus) where direct benefits to leaders appear unlikely. To test whether leaders could benefit indirectly we examined relatedness between leader-follower pairs and compared these levels to pairs who associated but did not have leader-follower relationship (neither ever led the other). We found the average relatedness value for leader-follower pairs was greater than expected based on chance. The same was not found when examining non leader-follower pairs. Additionally, relatedness for leader-follower pairs was positively correlated with association index values, but no correlation was found for this measure in non leader-follower pairs. Interestingly, haplotypes were not frequently shared between leader-follower pairs (25%). Together, these results suggest that bottlenose dolphin leaders have the opportunity to gain indirect benefits by leading relatives. These findings provide a potential mechanism for the maintenance of leadership in a highly dynamic fission-fusion population with few obvious direct benefits to leaders.

Wherever is my arm? Impaired upper limb position accuracy in complex regional pain syndrome.

Knowledge of the position of one's limbs is an essential component of daily function and relies on complex interactions of sensorimotor body schema-related information. Those with Complex Regional Pain Syndrome (CRPS) express difficulty in knowing where their affected limb is positioned. The aim of this study was to determine the degree to which experimental data supported the reported difficulty in limb position sense. A controlled experimental design was used to measure upper limb position accuracy amongst those with CRPS of one arm. Position accuracy was individually measured in both arms and compared to a known target position. Video captured each of 36 trials (half with arm in full view and half with vision obscured). The error in degrees between actual and known targets was determined using video analysis software. The Brief Pain Inventory measured pain. A subjective mental image representation of both upper limbs was documented. The CRPS group had moderate pain intensity and were significantly less accurate in positioning both the affected and unaffected limbs compared to controls (p<0.001). Position accuracy of the CRPS affected limb significantly improved with vision (8.3 degrees in view, 10.7 degrees not in view). Subjective mental representations of the affected limb were visualised as distorted. Evidence of bilateral arm positioning impairments in unilateral arm CRPS suggests that central mechanisms are involved. Cortical reorganisation in regions associated with the body schema (i.e. primary somatosensory and parietal cortices) is proposed as an explanation. The exact relationship between pain and limb position deficits requires further exploration.

Body perception disturbance: a contribution to pain in complex regional pain syndrome (CRPS).

In spite of pain in the CRPS limb, clinical observations show patients pay little attention to, and fail to care for, their affected limb as if it were not part of their body. Literature describes this phenomenon in terms of neurological neglect-like symptoms. This qualitative study sought to explore the nature of the phenomenon with a view to providing insights into central mechanisms and the relationship with pain. Twenty-seven participants who met the IASP CRPS classification were interviewed using qualitative methods to explore feelings and perceptions about their affected body parts. These semi-structured interviews were analysed utilising principles of grounded theory. Participants revealed bizarre perceptions about a part of their body and expressed a desperate desire to amputate this part despite the prospect of further pain and functional loss. A mismatch was experienced between the sensation of the limb and how it looked. Anatomical parts of the CRPS limb were erased in mental representations of the affected area. Pain generated a raised consciousness of the limb yet there was a lack of awareness as to its position. These feelings were about the CRPS limb only as the remaining unaffected body was felt to be normal. Findings suggest that there is a complex interaction between pain, disturbances in body perception and central remapping. Clinically, findings support the use of treatments that target cortical areas, which may reduce body perception disturbance and pain. We propose that body perception disturbance is a more appropriate term than 'neglect-like' symptoms to describe this phenomenon.