Search

Background: In recent years, there has been a growing interest in the use of neuromodulation as an alternative treatment option for chronic pain. Neuromodulation techniques, such as spinal cord stimulation (SCS), dorsal root ganglion (DRG) stimulation, deep brain stimulation (DBS), and peripheral nerve stimulation, have shown promising results in the management of various chronic pain conditions and involve targeted modulation of neural activity to alleviate pain and restore functional capacity. The autonomic nervous system (ANS) plays a crucial role in the regulation of various bodily functions including pain perception. However, the effects of neuromodulation on the ANS in the context of chronic pain remain poorly understood. This systematic review aimed to comprehensively assess the existing literature about the effects of neuromodulation on the ANS in chronic pain settings. Methods: Searches were conducted using four electronic databases (PubMed, EMBASE, SCOPUS, and Web of Science). The study protocol was registered before initiation of the review process. The Office of Health Assessment and Translation (OHAT) Risk of Bias tool was used to evaluate risk of bias. Results: A total of 43 studies were included, of which only one was an animal study. Several studies have reported more than one outcome parameter in the same population of chronic pain patients. Cardiovascular parameters were the most frequently used outcomes. More specifically, 18 outcome parameters were revealed to evaluate the function of the ANS, namely heart rate variability (n=17), arterial blood pressure (n=15), tissue oxygenation/perfusion (n=5), blood markers (n=6), multiunit postganglionic sympathetic nerve activity (n=4), skin temperature (n=3), skin conductance (n=3), cephalic autonomic symptoms (n=2), ventilatory frequency (n=2), vasomotor tone (n=1), baroreflex sensitivity (n=1), sympathetic innervation of the heart, neural activity of intrinsic cardiac neurons (n=1), vascular conductance (n=1), arterial diameter (n=1), blood pulse volume (n=1), and vagal efficiency (n=1). Most studies evaluated SCS (62.79%), followed by DBS (18.6%), peripheral nerve stimulation (9.3%), DRG stimulation (4.65%), and vagus nerve stimulation (4.65%). Overall, inconsistent results were revealed towards contribution of SCS, DBS, and peripheral nerve stimulation on ANS parameters. For DRG stimulation, included studies pointed towards a decrease in sympathetic activity. Conclusions: There are indications that neuromodulation alters the ANS, supported by high or moderate confidence in the body of evidence, however, heterogeneity in ANS outcome measures drives towards inconclusive results. Further research is warranted to elucidate the indirect or direct mechanisms of action on the ANS, with a potential benefit for optimisation of patient selection for these interventions. Systematic review protocol: PROSPERO (CRD42021297287).

Introduction: In the search for objective measures of therapeutic outcomes for patients with spinal cord stimulation (SCS) devices, various metrics of cardiac performance have been linked to pain as well as overall health. To track such measures at home, recent studies have incorporated wearables to monitor cardiac activity over months or years. The drawbacks to wearables, such as patient compliance, would be obviated by on-device sensing that incorporates the SCS lead. This study sought to evaluate the feasibility of using SCS leads to record cardiac electrograms.Methods: The quality of signals sensed by externalized, percutaneous leads in the thoracic spine of 10 subjects at the end of their SCS trial were characterized across various electrode configurations and postures by detecting R-peaks and calculating signal-to-noise ratio (SNR). In a subset of 5 subjects, cardiac metrics were then compared to those measured simultaneously with a wearable.Results: The average signal quality was acceptable for R-peak detection (i.e., SNR > 5) for all configurations and positions across all 10 subjects, with higher signal quality achieved when recording in resting positions. Notably, the spinal lead recordings enabled more reliable beat detection compared to the wearable (n = 29 recording pairs; p < 0.001). When excluding wearable recordings with over 35% missed beats, the inter-beat intervals across devices were highly correlated (n = 22 recording pairs; Pearson correlation: R = 0.99, p < 0.001). Further comparisons in these aligned wearable and corresponding spinal-lead recordings revealed significant differences in the frequency domain metrics (i.e., absolute and normalized high and low frequency HRV power, p < 0.05), but not in time domain HRV parameters.Discussion: The ability of an implanted SCS system to record electrocardiograms, as demonstrated here, could provide the basis of automated SCS therapy by tracking potential biomarkers of the patient’s overall health state without the need for additional external devices.

BackgroundSpinal Cord Stimulation (SCS) may provide pain relief in patients with therapy-refractory Persistent Spinal Pain Syndrome Type II (PSPS-T2). Despite the evidence that SCS can reduce disability and reduce pain medication usage, only 25% of the patients is able to completely omit pain medication usage after 12 months of SCS. To tackle the high burden of patients who consume a lot of pain medication, tapering programs could be initiated before starting a trajectory with SCS. The current objective is to examine whether a pain medication tapering program before SCS alters disability in PSPS-T2 patients compared to no tapering program.Methods and designA three-arm, parallel-group multicenter randomized controlled trial will be conducted including 195 patients who will be randomized (1:1:1) to either (a) a standardized pain medication tapering program, (b) a personalized pain medication tapering program, or (c) no tapering program before SCS implantation, all with a follow-up period until 12 months after implantation. The primary outcome is disability. The secondary outcomes are pain intensity, health-related quality of life, participation, domains affected by substance use, anxiety and depression, medication usage, psychological constructs, sleep, symptoms of central sensitization, and healthcare expenditure.DiscussionWithin the PIANISSIMO project we propose a way to reduce the risks of adverse events, medication-induced hyperalgesia, tolerance, and dependence by providing pain medication tapering before SCS. Due to the lack of a commonly accepted in-hospital tapering approach, two different tapering programs will be evaluated in this study. If pain medication tapering programs are deemed to be more effective than no tapering on disability, this would add to the evidence towards an improved patient-centered care model in this patient group and set a clear path to advocate for pain medication tapering before SCS as the new standard treatment guideline for these patients.Trial registrationClinicalTrials.gov NCT05861609. Registered on May 17, 2023.

Introduction: Spinal pain syndromes have a severe impact on the patient's sex life, contributing to a decrease in sexual function and sexual satisfaction. Despite the importance of sexual health on mental and physical wellbeing, sexual health is rarely discussed during consultations. Research question: The aim of this study is to explore to what extent influencing factors can alter the discussion about sexual health during consultations. More specifically, we will evaluate the influence of healthcare profession, sex of the patient and the surgical approach that is proposed. Material and methods: An online survey was sent to neurosurgeons, pain physicians and orthopedists in Belgium and The Netherlands in April 2019. Participants were asked about; counseling routine, knowledge, and opinion on sexual health. Answers were scored on a 5-point Likert scale. Independence between the response levels and type of surgery as well as profession were tested. Results: In total, 350 respondents were approached of whom 57 completed the survey. The majority of respondents (61.4%) indicated that they rarely or never discussed sexual disturbances. Profession and type of surgery had an influence on discussing erectile dysfunction, retrograde ejaculation, and alterations in orgasms. Thirty-five percent of healthcare providers considered it the patient's responsibility to bring up the subject of sexual health. Discussion and conclusion: Sexual health is rarely addressed by healthcare providers during spinal care. Profession as well as type of surgery seems to play a role on whether sexual health is discussed during consultations.

IntroductionRecent evidence supports the contribution of gut microbiota dysbiosis to the pathophysiology of rheumatic diseases, neuropathic pain, and neurodegenerative disorders. The bidirectional gut-brain communication network and the occurrence of chronic pain both involve contributions of the autonomic nervous system and the hypothalamic pituitary adrenal axis. Nevertheless, the current understanding of the association between gut microbiota and chronic pain is still not clear. Therefore, the aim of this study is to systematically evaluate the existing knowledge about gut microbiota alterations in chronic pain conditions.MethodsFour databases were consulted for this systematic literature review: PubMed, Web of Science, Scopus, and Embase. The Newcastle-Ottawa Scale was used to assess the risk of bias. The study protocol was prospectively registered at the International prospective register of systematic reviews (PROSPERO, CRD42023430115). Alpha-diversity, β-diversity, and relative abundance at different taxonomic levels were summarized qualitatively, and quantitatively if possible.ResultsThe initial database search identified a total of 3544 unique studies, of which 21 studies were eventually included in the systematic review and 11 in the meta-analysis. Decreases in alpha-diversity were revealed in chronic pain patients compared to controls for several metrics: observed species (SMD= -0.201, 95% CI from -0.04 to -0.36, p=0.01), Shannon index (SMD= -0.27, 95% CI from -0.11 to -0.43, p

BackgroundThe increased availability of web-based medical information has encouraged patients with chronic pain to seek health care information from multiple sources, such as consultation with health care providers combined with web-based information. The type and quality of information that is available on the web is very heterogeneous, in terms of content, reliability, and trustworthiness. To date, no studies have evaluated what information is available about neuromodulation on the web for patients with chronic pain. ObjectiveThis study aims to explore the type, quality, and content of web-based information regarding spinal cord stimulation (SCS) for chronic pain that is freely available and targeted at health care consumers. MethodsThe social listening tool Awario was used to search Facebook (Meta Platforms, Inc), Twitter (Twitter, Inc), YouTube (Google LLC), Instagram (Meta Platforms, Inc), blogs, and the web for suitable hits with “pain” and “neuromodulation” as keywords. Quality appraisal of the extracted information was performed using the DISCERN instrument. A thematic analysis through inductive coding was conducted. ResultsThe initial search identified 2174 entries, of which 630 (28.98%) entries were eventually withheld, which could be categorized as web pages, including news and blogs (114/630, 18.1%); Reddit (Reddit, Inc) posts (32/630, 5.1%); Vimeo (Vimeo, Inc) hits (38/630, 6%); or YouTube (Google LLC) hits (446/630, 70.8%). Most posts originated in the United States (519/630, 82.4%). Regarding the content of information, 66.2% (383/579) of the entries discussed (fully discussed or partially discussed) how SCS works. In total, 55.6% (322/579) of the entries did not elaborate on the fact that there may be >1 potential treatment choice and 47.7% (276/579) did not discuss the influence of SCS on the overall quality of life. The inductive coding revealed 4 main themes. The first theme of pain and the burden of pain (1274/8886, 14.34% coding references) explained about pain, pain management, individual impact of pain, and patient experiences. The second theme included neuromodulation as a treatment approach (3258/8886, 36.66% coding references), incorporating the background on neuromodulation, patient-centered care, SCS therapy, and risks. Third, several device-related aspects (1722/8886, 19.38% coding references) were presented. As a final theme, patient benefits and testimonials of treatment with SCS (2632/8886, 29.62% coding references) were revealed with subthemes regarding patient benefits, eligibility, and testimonials and expectations. ConclusionsHealth care consumers have access to web-based information about SCS, where details about the surgical procedures, the type of material, working mechanisms, risks, patient expectations, testimonials, and the potential benefits of this therapy are discussed. The reliability, trustworthiness, and correctness of web-based sources should be carefully considered before automatically relying on the content.

Objective: To identify the essential attributes of biopsychosocial rehabilitation for chronic low back pain in the working population. Design: A concept analysis was conducted according to the 8-step method of Walker and Avant. This framework provides a clear concept and theoretical and operational definitions. Methods: Five databases were searched, followed by a systematic screening. Subsequently, attributes, illustrative cases, antecedents, consequences and empirical referents were formulated. Results: Of the 3793 studies identified, 42 unique references were included. Eleven attributes were identified: therapeutic exercise, psychological support, education, personalization, self-management, participation, follow-up, practice standard, goal-setting, social support, and dietary advice. Subsequently, illustrative cases were described. Antecedents, such as motivation, preparedness and a multidisciplinary team, were found, together with consequences such as decreased pain, less sick-leave and increased function and work status. Finally, examples of empirical referents were given. Conclusion: This study identified the attributes that are necessary to develop biopsychosocial rehabilitation intervention programmes for chronic low back pain. The defined concept of biopsychosocial rehabilitation for chronic low back pain may serve as a solid base to further develop and apply interventions. Future research should focus on the objectification of biopsychosocial rehabilitation and conceptualization regarding how personalization is done.

Abstract Background Posttraumatic stress disorder (PTSD) can occur after trauma. While PTSD management strategies include first-line pharmacotherapy and psychotherapy, mind–body therapies, such as yoga, are applied in the PTSD population. This overview aimed to summarize the effectiveness of yoga interventions on PTSD symptoms in adults in a systematic review (SR) including randomized controlled trials (RCTs). Method We searched for SR with or without meta-analysis of RCTs involving adults with PTSD diagnosis or trauma history. The search was conducted until April 2022, through six databases (Cochrane Database, MEDLINE (Pubmed), Scopus, Embase, CINHAL and PEDro). The primary outcome was the evolution of PTSD symptoms throughout the intervention. Secondary outcomes included follow-up, safety, adherence, and cost of the intervention. Two authors independently performed the selection, data extraction and risk of bias assessment with the AMSTAR 2 tool and overlap calculation. This overview is a qualitative summary of the results obtained in the selected studies. Results Eleven SRs were analyzed, of which 8 included meta-analyses. The overlap between studies was considered very high (corrected covered area of 21%). Fifty-nine RCTs involving 4434 participants were included. Yoga had a significant small-to-moderate effect-size on PTSD symptom decrease in 7 SRs and non-significant effects in 1 SR with meta-analysis. All SR without meta-analysis found beneficial effects of yoga on PTSD. Secondary outcomes were not sufficiently assessed to provide clear evidence. Results should be interpreted with caution as 1 SR was rated as at moderate risk of bias, 3 as low and 7 as critically low. Conclusions While yoga therapy seems promising for decreasing PTSD symptoms, future research should standardize yoga therapy duration/frequency/type and consider long-term efficacy to better delineate yoga therapy efficacy in PTSD patients.

Abstract Background Integrating information on bodily functions, pain intensity and quality of life into one composite measure of a holistic responder has recently been proposed as a useful method to evaluate treatment efficacy of spinal cord stimulation (SCS) in patients with therapy-refractory persistent spinal pain syndrome type II (PSPS-T2). Previous studies already demonstrated the efficacy of standard SCS over best medical treatment (BMT) and the superiority of new subthreshold (i.e. paresthesia free) SCS paradigms compared to standard SCS. Nevertheless, the efficacy of subthreshold SCS compared to BMT has not yet been investigated in patients with PSPS-T2, neither with unidimensional outcomes nor with a composite measure. The current objective is to examine whether subthreshold SCS, compared to BMT, provided to patients with PSPS-T2 results in a different proportion of clinical holistic responders (as composite measure) at 6 months. Methods A two-arm multicentre randomised controlled trial will be conducted whereby 114 patients will be randomised (1:1) to (a) BMT or (b) paresthesia-free SCS. After a follow-up period of 6 months (primary time endpoint), patients receive the opportunity to cross over towards the other treatment group. The primary outcome is the proportion of clinical holistic responders at 6 months (i.e. a composite measure of pain intensity, medication, disability, health-related quality of life and patient satisfaction). The secondary outcomes are work status, self-management, anxiety, depression and healthcare expenditure. Discussion Within the TRADITION project, we propose to shift the focus from a unidimensional outcome measure towards a composite measure as primary outcome measure to evaluate the efficacy of currently used subthreshold SCS paradigms. The lack of methodologically rigorous trials exploring the clinical efficacy and socio-economic consequences of subthreshold SCS paradigms is pressing, especially in light of the growing burden of PSPS-T2 on the society. Trial registration ClinicalTrials.gov NCT05169047. Registered on December 23, 2021

Abstract Background For patients with therapy-refractory persistent spinal pain syndrome type II (PSPS-T2), spinal cord stimulation (SCS) may serve as an effective minimally invasive treatment. Despite the evidence that SCS can improve return to work (RTW), only 9.5 to 14% of patients implanted with SCS are effectively capable of returning to work. Thus, it seems that current post-operative interventions are not effective for achieving RTW after SCS implantation in clinical practice. The current objective is to examine whether a personalised biopsychosocial rehabilitation programme specifically targeting RTW alters the work ability in PSPS-T2 patients after SCS implantation compared to usual care. Methods A two-arm, parallel-group multicentre randomised controlled trial will be conducted including 112 patients who will be randomised (1:1) to either (a) a personalised biopsychosocial RTW rehabilitation programme of 14 weeks or (b) a usual care arm, both with a follow-up period until 12 months after the intervention. The primary outcome is work ability. The secondary outcomes are work status and participation, pain intensity, health-related quality of life, physical activity and functional disability, functional capacities, sleep quality, kinesiophobia, self-management, anxiety, depression and healthcare expenditure. Discussion Within the OPERA project, we propose a multidisciplinary personalised biopsychosocial rehabilitation programme specifically targeting RTW for patients implanted with SCS, to tackle the high socio-economic burden of patients that are not re-entering the labour market. The awareness is growing that the burden of PSPS-T2 on our society is expected to increase over time due to the annual increase of spinal surgeries. However, innovative and methodologically rigorous trials exploring the potential to decrease the socio-economic burden when patients initiate a trajectory with SCS are essentially lacking. Trial registration ClinicalTrials.gov NCT05269212. Registered on 7 March 2022.

Background and Objectives: Botulinum toxin injections are commonly used for the treatment of spasticity. However, injection procedures are associated with pain and procedural anxiety. While pharmacological approaches are commonly used to reduce these, innovative technology might be considered as a potential non-pharmacological alternative. Given this context, immersive virtual reality (VR) has shown effectiveness in the management of procedural pain. Our retrospective pilot study aimed to assess the potential added value of virtual reality in the management of pain and anxiety during intramuscular injections of botulinum toxin. Materials and Methods: Seventeen adult patients receiving botulinum toxin injections were included. A numerical rating scale was used to assess pain and anxiety during the injection procedure. The patients reported the pain experienced during previous injections without VR before injection and the pain experienced in the current procedure with VR after the end of the procedure. The level of satisfaction of VR experience, whether or not they agreed to reuse VR for the subsequent toxin botulinum injection, and whether or not they would recommend VR to other patients were assessed. Results: The use of virtual reality led to a decrease of 1.8 pain-related points compared to the procedure without technology. No significant improvement in the level of anxiety was reported. Patients were very satisfied with their VR experiences (7.9 out of 10), and many would agree to reuse VR in their next injection procedure (88%) and to recommend the use of VR in other patients (100%). Conclusion: VR was useful for managing procedural pain related to botulinum toxin injection in adults, with a high level of satisfaction reported by the patients. VR should be considered as a valuable alternative to pharmacological approaches to manage procedural pain during botulinum toxin injection in adults.

The Coronavirus disease 2019 (COVID-19) pandemic exerted a tremendous pressure on the healthcare system, people's social life, mental health and financial status with profound implications for the general population. The exact impact of the pandemic on the overall physical, mental and social wellbeing of COVID-19 infection survivors on the long term has not yet been explored in a thorough way. Based on the reporting of persistent pain, fatigue and dyspnea symptoms by these survivors, it is our hypothesis that their quality of life will be extremely impacted, as is observed in patients with chronic pain. Therefore, the first aim of this study was to perform an in-depth evaluation of the quality of life of post-COVID-19 infected persons. The second aim was to compare the quality of life of these persons with a normative population and with patients with chronic pain. Health-related quality of life, as a measure for a person's overall physical, mental, and social wellbeing, was measured with the 3-level EQ5D in 547 post-COVID-19 infected persons. These data were compared to reference data from normal population records for Belgium and to data from patients with chronic pain after spinal surgery with two-way analyses of variance. In total, 89.58% of the post-COVID-19 infected persons reported pain/discomfort and 82.45% indicated limitations when performing usual activities, when evaluated 287 days (SD: 150) after the infection. Self-care was preserved in most post-COVID-19 persons, whereby only 13.16% indicated problems. The mean EQ5D-3L index score was 0.57 (SD: 0.23) and EQ5D VAS mean score was 56.6 (SD: 18.2). The mean index score for the normative population was significantly higher than for COVID-19 infected persons [mean difference of 0.31 (95% from 0.29 to 0.33), p < 0.01] while the mean score of chronic pain patients was significantly lower than the score of COVID-19 infected persons [mean difference of −0.31 (95% from −0.29 to −0.33), p < 0.01]. Compared to age-and sex adjusted reference data, health-related quality of life of persons with long COVID is severely impacted. In relation to patients with chronic pain after spinal surgery, the quality of life of post-COVID-19 infected persons seemed to be better.Clinical trial registrationhttps://www.clinicaltrials.gov/, identifier: NCT04912778.

BackgroundVirtual reality (VR) is a computer technology that immerses a user in a completely different reality. The application of VR in acute pain settings is well established. However, in chronic pain, the applications and outcome parameters influenced by VR are less clear. ObjectiveThis review aimed to systematically identify all outcome parameters that are reported in relation to VR in patients with chronic pain. MethodsA total of 4 electronic databases (PubMed, Scopus, Web of Science, and Embase) were searched for relevant studies. Multilevel random-effect meta-analyses were performed, whereby the standardized mean difference was chosen as the effect size to denote the difference between measurements before and after a VR intervention. ResultsThe initial database search identified 1430 studies, of which 41 (2.87%) were eventually included in the systematic review. Evidence has been found for the effects of VR on pain, functioning, mobility, functional capacity, psychological outcomes, quality of life, neuropsychological outcomes, and physical sensations. The overall effect size (a total of 194 effect sizes from 25 studies) based on a three level meta-analysis was estimated at 1.22 (95% CI 0.55-1.89; z=3.56; P

Spinal cord (SC) anatomy is often assimilated to a morphologically encapsulated neural entity, but its functional anatomy remains only partially understood. We hypothesized that it could be possible to re-explore SC neural networks by performing live electrostimulation mapping, based on “super-selective” spinal cord stimulation (SCS), originally designed as a therapeutical tool to address chronic refractory pain. As a starting point, we initiated a systematic SCS lead programming approach using live electrostimulation mapping on a chronic refractory perineal pain patient, previously implanted with multicolumn SCS at the level of the conus medullaris (T12-L1). It appeared possible to (re-)explore the classical anatomy of the conus medullaris using statistical correlations of paresthesia coverage mappings, resulting from 165 different electrical configurations tested. We highlighted that sacral dermatomes were not only located more medially but also deeper than lumbar dermatomes at the level of the conus medullaris, in contrast with classical anatomical descriptions of SC somatotopical organization. As we were finally able to find a morphofunctional description of “Philippe–Gombault’s triangle” in 19th-century historical textbooks of neuroanatomy, remarkably matching these conclusions, the concept of “neuro-fiber mapping” was introduced.

Fatigue, pain, headache, brain fog, anosmia, ageusia, mood symptoms, and sleep disorders are symptoms commonly experienced by people with post-COVID-19 condition. These symptoms could be considered as manifestations of central sensitization. The aim of this study is to evaluate whether there are indicators of central sensitization by using experimental pain measurements and to determine their association with patient-reported outcome measures (PROMs). A cross-sectional study including 42 patients after COVID-19 infection was conducted. The central sensitization inventory (CSI) was administered as a PROM to evaluate central-sensitization-associated symptoms. Pressure pain thresholds (PPT), temporal summation, and descending nociceptive pain inhibition (CPM) were assessed as experimental pain measurements. The median score on the CSI was 46.5 (Q1–Q3: 33–54). The presence of central-sensitization-associated symptoms was seen in 64.3% of patients based on the CSI (≥40/100 points). A deficient CPM was seen in 12% and 14% of patients when measured at the trapezius and rectus femoris, respectively. A negative correlation between pressure sensitivity on the rectus femoris and the CSI score (r = −0.36, 95%CI −0.13 to −0.65, p = 0.007) was observed. Central-sensitization-associated symptoms were present in up to 64.3% of patients post-COVID-19 infection, based on a PROM, i.e., the CSI. A more objective evaluation of nociceptive processing through experimental pain measurements was less suggestive of indicators of central sensitization. Only a small negative correlation between pressure sensitivity and the CSI was observed, thereby pointing towards the discrepancy between the CSI and experimental pain measurements and presumably the complementary need for both to evaluate potential indicators of central sensitization in this population.

This cross-sectional study explored associations between demographics, pain intensity and cognitions on the one hand and healthcare use (HCU) on the other hand in people undergoing surgery for lumbar radiculopathy. HCU during the 2 months preceding surgery was evaluated using a retrospective questionnaire. Demographics included sex, age and level of education and equivalent income. Back and leg pain intensity were evaluated using a visual analogue scale. Pain cognitions were assessed with the Tampa scale of kinesiophobia, the pain catastrophizing scale and the pain vigilance and awareness questionnaire. The sample comprised 120 participants (52% males; 49 years (Quartile (Q)1–Q3: 37.3–57.43)). The number of visits to the general practitioner was associated with sex (incidence rate ratio (IRR) for males = 0.811; p = 0.050), pain catastrophizing (IRR = 1.010; p = 0.041), pain magnification (IRR = 1.058; p = 0.004) and leg pain intensity (IRR = 1.004; p = 0.038). The number of neurosurgeon visits was associated with level of education (IRR moderate education = 1.518; p = 0.016 (reference: low education)). Receiving zero physiotherapy visits was associated with higher back pain intensity (Beta = 0.018; p = 0.028). Highest level of analgesics used was associated with sex (IRR for males = 0.502; p = 0.047) and leg pain (IRR = 1.014; p = 0.034). Only the association between general practitioner visits and pain magnification remained significant in multivariable analyses (IRR = 1.061; p = 0.033). The results suggest a rather indirect relationship between HCU and demographics, pain intensity and cognitions, involving a potential interplay between several patient- and healthcare system-related factors.

Pain after an acute Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) condition (post-COVID pain) is becoming a new healthcare emergency. Precision medicine refers to an evidence-based method of grouping patients based on their diagnostic/symptom presentation and then tailoring specific treatments accordingly. Evidence suggests that post-COVID pain can be categorized as nociceptive (i.e., pain attributable to the activation of the peripheral receptive terminals of primary afferent neurons in response to noxious chemical, mechanical, or thermal stimuli), neuropathic (i.e., pain associated with a lesion or disease of the somatosensory nervous system and limited to a “neuroanatomically plausible” distribution of the system), nociplastic (i.e., pain arising from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain), or mixed type (when two pain phenotypes co-exist). Each of these pain phenotypes may require a different treatment approach to maximize treatment effectiveness. Accordingly, the ability to classify post-COVID pain patients into one of these phenotypes would likely be critical for producing successful treatment outcomes. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system provide a framework for classifying pain within a precision pain medicine approach. Here we present data supporting the possibility of grouping patients with post-COVID pain into pain phenotypes, using the 2021 IASP classification criteria, with a specific focus on nociplastic pain, which is probably the primary mechanism involved in post-COVID pain. Nociplastic pain, which is usually associated with comorbid symptomology (e.g., poor sleep quality, fatigue, cognitive–emotional disturbances, etc.) and is considered to be more difficult to treat than other pain types, may require a more nuanced multimodal treatment approach to achieve better treatment outcomes.

Virtual reality has proven to be an effective approach to decrease pain in acute settings, both in adults and children. The aim of this study is to evaluate whether virtual reality (VR) could reduce pain during an intrathecal pump refill procedure in children receiving intrathecal drug delivery, compared to a standard refill procedure. This is a three-arm crossover randomized controlled trial, evaluating the effect of VR on pain in children with cerebral palsy undergoing an intrathecal pump refill compared to a standard refill and a refill with distraction (watching a video). Pain was evaluated using the Wong–Baker Faces Scale. Secondary outcomes were procedural pain, fear, state anxiety, the incidence of adverse events and satisfaction. Six children participated in this study, whereby all children underwent the three conditions. Five children indicated an equal of lower pain score during VR, compared to a standard refill. This finding of an equal or lower pain intensity score for the VR condition compared to the control condition was also revealed by the ratings of the parents, physician and the researcher. The influence of VR on anxiety and fear seem to be in line with the influence of watching a video. In terms of satisfaction, all children and parents agreed with the statement that they would like to use VR again for a next refill. Due to the lack of adverse events, the high degree of satisfaction of children with VR and the decreased pain levels after a refill with VR, physicians may aim to explore the implementation of VR during intrathecal pump refill procedures in children in a daily clinical routine care setting.

Representatives of neuromodulation device manufacturers are expected to facilitate the relationship between patients and healthcare providers. Nevertheless, the goals, expectations, and definition of success for neuromodulation for pain have not yet been explored. Representatives present at the 2nd Joint Congress of the INS European Chapters in September 2021 completed a survey to ascertain their opinions about the goals to achieve with neuromodulation, the factors that they expect to change, and their definition of success for neuromodulation. In total, 39 representatives completed the survey. To provide excellent service for patients (22.4%), to become a trusted partner for physicians (21.5%), and to provide excellent service for physicians (20.7%) were the highest ranked goals. The most frequently reported factors that were expected to change were pain intensity (23.1%), patient satisfaction (19.7%), mobility/functioning (14.5%), and capacity to return to work (13.7%). Within the definitions of success, increased quality of life of the patient was stated in 21% of the definitions, closely followed by pain control (19.3%) and happiness/patient satisfaction (15.8%). The goals of representatives of neuromodulation device manufacturers seem to focus on ensuring a good relationship with physicians on the one hand and providing good service towards patients on the other hand, whereby pain control, quality of life, and patient satisfaction seem to be important for company representatives.

Spinal cord stimulation (SCS) is an effective and validated treatment to address chronic refractory neuropathic pain in persistent spinal pain syndrome-type 2 (PSPS-T2) patients. Surgical SCS lead placement is traditionally performed under general anesthesia due to its invasiveness. In parallel, recent works have suggested that awake anesthesia (AA), consisting of target controlled intra-venous anesthesia (TCIVA), could be an interesting tool to optimize lead anatomical placement using patient intra-operative feedback. We hypothesized that combining AA with minimal invasive surgery (MIS) could improve SCS outcomes. The goal of this study was to evaluate SCS lead performance (defined by the area of pain adequately covered by paraesthesia generated via SCS), using an intraoperative objective quantitative mapping tool, and secondarily, to assess pain relief, functional improvement and change in quality of life with a composite score. We analyzed data from a prospective multicenter study (ESTIMET) to compare the outcomes of 115 patients implanted with MIS under AA (MISAA group) or general anesthesia (MISGA group), or by laminectomy under general anesthesia (LGA group). All in all, awake surgery appears to show significantly better performance than general anesthesia in terms of patient pain coverage (65% vs. 34–62%), pain surface (50–76% vs. 50–61%) and pain intensity (65% vs. 35–40%), as well as improved secondary outcomes (quality of life, functional disability and depression). One step further, our results suggest that MISAA combined with intra-operative hypnosis could potentialize patient intraoperative cooperation and could be proposed as a personalized package offered to PSPS-T2 patients eligible for SCS implantation in highly dedicated neuromodulation centers.

A high number of online support groups have been created on social media platforms to reinforce personal empowerment and social support. The goal of this study was to perform natural language processing by constructing a bag-of-words model and conducting topic modelling based on posts extracted from a chronic pain community. The subreddit called ‘r/sChronicPain’ was used to investigate communication on social media platforms for chronic pain patients. After data cleaning and lemmatisation, a word cloud was constructed, and the most frequent words and most frequent body regions were counted. Latent Dirichlet allocation was used to perform topic modelling. In the final analysis set, 937 unique posts were included. The most frequent word was ‘pain’, followed by ‘doctor’, ‘day’, ‘feel’, ‘back’, ‘year’, and ‘time’. Concerning the body regions, ‘back’ was most often mentioned, followed by ‘neck’ and ‘leg’. Based on coherence scores, one topic was extracted with ‘pain’ as the keyword with the highest weight. In line with the allocation of chronic low-back pain as a major health problem and increasing prevalence, back pain was most often mentioned. It seems that the primarily treatment trajectories that are proposed by medical physicians are discussed on social media, compared to interventions by other healthcare providers.

Chronic pain remains a very difficult condition to manage for healthcare workers and patients. Different options are being considered and a biopsychosocial approach seems to have the most benefit, since chronic pain influences biological, psychological and social factors. A conservative approach with medication is the most common type of treatment in chronic pain patients; however, a lot of side effects are often induced. Therefore, a premium is set on novel nonpharmacological therapy options for chronic pain, such as psychological interventions. Previous research has demonstrated that resilience is a very important aspect in coping with chronic pain. A more recent type of cognitive-behavioural therapy is Acceptance and Commitment Therapy, in which psychological flexibility is intended to be the end result. In this manuscript, current evidence is used to explain why and how a comprehensive and multimodal treatment for patients with chronic pain can be applied in clinical practice. This multimodal treatment consists of a combination of pain neuroscience education and cognitive-behavioural therapy, more specifically Acceptance and Commitment Therapy. The aim is to provide a clinical guideline on how to contribute to greater flexibility and resilience in patients with chronic pain.

In the past decade, neuromodulation as a treatment option for pain took a huge interest in innovating and developing more effective paradigms to conquer chronic pain syndromes [...]

To improve pain relief for refractory pain condition, spinal cord stimulation (SCS) needs to target the dedicated neuronal fibers within the dorsal columns. Intraoperative feedback from the patient can optimize lead placement but requires “awake surgery”, allowing interaction between patient and surgeon. This can produce negative effects like anxiety and stress. To better manage these aspects, we propose to combine intraoperative hypnosis with awake anesthesia. Seventy-four patients (35 females, 22–80 years) presenting with chronic refractory pain, were offered intraoperative hypnosis during awake SCS lead implantation. Interactive conversational hypnosis was used as well as interactive touch, which was enhanced during painful moments during the lead intraoperative programming. All patients participated actively during the intraoperative testing which helped to optimize the lead positioning. They kept an extremely positive memory of the surgery and of the hypnotic experience, despite some painful moments. Pain could be reduced in these patients by using interactions and touch, which works on Gate Control modulation. Positive memory was reinforced by congratulations to create self-confidence and to induce positive expectations, which could reinforce the Diffuse Noxious Inhibitory Controls at the spinal level. Cooperation was improved because the patient was actively participating and thus, much more alert when feedback was required. Combining intraoperative hypnosis with awake anesthesia appears helpful for SCS lead implantation. It enhances patient cooperation, allows optimization of lead positioning, and leads to better pain control, positive and resourceful memory.

While paresthesia-based Spinal Cord Stimulation (SCS) has been proven effective as treatment for chronic neuropathic pain, its initial benefits may lead to the development of “Failed SCS Syndrome’ (FSCSS) defined as decrease over time related to Loss of Efficacy (LoE) with or without Loss of Coverage (LoC). Development of technologies associating new paresthesia-free stimulation waveforms and implanted pulse generator adapters provide opportunities to manage patients with LoE. The main goal of our study was to investigate salvage procedures, through neurostimulation adapters, in patients already implanted with SCS and experiencing LoE. We retrospectively analyzed a cohort of patients who were offered new SCS programs/waveforms through an implanted adapter between 2018 and 2021. Patients were evaluated before and at 1-, 3-, 6- and 12-month follow-ups. Outcomes included pain intensity rating with a Visual Analog Scale (VAS), pain/coverage mappings and stimulation preferences. Last follow-up evaluations (N = 27) showed significant improvement in VAS (p = 0.0001), ODI (p = 0.021) and quality of life (p = 0.023). In the 11/27 patients with LoC, SCS efficacy on pain intensity (36.89%) was accompanied via paresthesia coverage recovery (55.57%) and pain surface decrease (47.01%). At 12-month follow-up, 81.3% preferred to keep tonic stimulation in their waveform portfolio. SCS conversion using adapters appears promising as a salvage solution, with an emphasis on paresthesia recapturing enabled via spatial retargeting. In light of these results, adapters could be integrated in SCS rescue algorithms or should be considered in SCS rescue.

While spinal cord stimulation (SCS) is a well-established therapy to address refractory persistent spinal pain syndrome after spinal surgery (PSPS-T2), its lack of spatial selectivity and reported discomfort due to positional effects can be considered as significant limitations. As alternatives, new waveforms, such as burst stimulation and different spatial neural targets, such as dorsal root ganglion stimulation (DRGS), have shown promising results. Comparisons between DRGS and standard SCS, or their combination, have never been studied on the same patients. “BOOST DRG” is the first prospective, randomized, double-blinded, crossover study to compare SCS vs. DRGS vs. SCS+DRGS. Sixty-six PSPS-T2 patients will be recruited internationally in three centers. Before crossing over, patients will receive each stimulation modality for 1 month, using tonic conventional stimulation. After 3 months, stimulation will consist in switching to burst for 1 month, and patients will choose which modality/waveform they receive and will then be reassessed at 6 and 12 months. In addition to our primary outcome based on pain rating, this study is designed to assess quality of life, functional disability, psychological distress, pain surface coverage, global impression of change, medication quantification, adverse events, brain functional imaging and electroencephalography, with the objective being to provide a multidimensional insight based on composite pain assessment.

Continuous Intrathecal Drug Delivery through an implanted pump is a well-known therapeutic option for the management of chronic pain and severe disabling spasticity. To have a successful therapy, pump refills need to be performed at regular time intervals after implantation. In line with the increased applications of Hospital at Home, these refill procedures might be performed at the patient’s home. The aim of this pilot study is to evaluate the feasibility, safety, and effectiveness of intrathecal pump refill procedures at home. Twenty patients were included whereby pump refill procedures were conducted at the patient’s home. To enable contact with the hospital, a video connection was set-up. Tele-ultrasound was used as post-refill verification. All procedures were successfully performed with complete patient satisfaction. Ninety-five percent of the patients felt safe during the procedure, and 95% of the procedures felt safe according to the physician. All patients indicated that they preferred their next refill at home. The median time consumption for the physician/nurse at the patient’s home was 26 min and for the researcher at the hospital 15 min. In light of quality enhancement programs and personalized care, it is important to continue urgent pain management procedures in a safe way, even during a pandemic.

Patients recovered from a COVID-19 infection often report vague symptoms of fatigue or dyspnoea, comparable to the manifestations in patients with central sensitisation. The hypothesis was that central sensitisation could be the underlying common aetiology in both patient populations. This study explored the presence of symptoms of central sensitisation, and the association with functional status and health-related quality of life, in patients post COVID-19 infection. Patients who were previously infected with COVID-19 filled out the Central Sensitisation Inventory (CSI), the Post-COVID-19 Functional Status (PCFS) Scale and the EuroQol with five dimensions, through an online survey. Eventually, 567 persons completed the survey. In total, 29.73% of the persons had a score of p < 0.001). This survey indicated the presence of symptoms of central sensitisation in more than 70% of patients post COVID-19 infection, suggesting towards the need for patient education and multimodal rehabilitation, to target nociplastic pain.

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), (Failed Back Surgery Syndrome), dramatically impacts on patient quality of life, as evidenced by Health-Related Quality of Life (HRQoL) assessment tools. However, the importance of functioning, pain perception and psychological status in HRQoL can substantially vary between subjects. Our goal was to extract patient profiles based on HRQoL dimensions in a sample of PSPS-T2 patients and to identify factors associated with these profiles. Two classes were clearly identified using a mixture of mixed effect models from a clinical data set of 200 patients enrolled in “PREDIBACK”, a multicenter observational prospective study including PSPS-T2 patients with one-year follow-up. We observed that HRQoL was more impacted by functional disability for first class patients (n = 136), and by pain perception for second class patients (n = 62). Males that perceive their work as physical were more impacted by disability than pain intensity. Lower education level, lack of adaptive coping strategies and higher pain intensity were significantly associated with HRQoL being more impacted by pain perception. The identification of such classes allows for a better understanding of HRQoL dimensions and opens the gate towards optimized health-related quality of life evaluation and personalized pain management.

Persistent pain after spinal surgery can be successfully addressed by spinal cord stimulation (SCS). International guidelines strongly recommend that a lead trial be performed before any permanent implantation. Recent clinical data highlight some major limitations of this approach. First, it appears that patient outco mes, with or without lead trial, are similar. In contrast, during trialing, infection rate drops drastically within time and can compromise the therapy. Using composite pain assessment experience and previous research, we hypothesized that machine learning models could be robust screening tools and reliable predictors of long-term SCS efficacy. We developed several algorithms including logistic regression, regularized logistic regression (RLR), naive Bayes classifier, artificial neural networks, random forest and gradient-boosted trees to test this hypothesis and to perform internal and external validations, the objective being to confront model predictions with lead trial results using a 1-year composite outcome from 103 patients. While almost all models have demonstrated superiority on lead trialing, the RLR model appears to represent the best compromise between complexity and interpretability in the prediction of SCS efficacy. These results underscore the need to use AI-based predictive medicine, as a synergistic mathematical approach, aimed at helping implanters to optimize their clinical choices on daily practice.

New waveforms have changed the field of Spinal Cord Stimulation (SCS) to optimize therapy outcomes, among which is High-Dose SCS (HD-SCS). Missing observations are often encountered when conducting clinical trials in this field. In this study, different approaches with varying assumptions were constructed to evaluate how conclusions may be influenced by these assumptions. The aim is to perform a tipping point sensitivity analysis to evaluate the influence of missing data on the overall conclusion regarding the effectiveness of HD-SCS on disability. Data from the Discover study were used, in which 185 patients with Failed Back Surgery Syndrome were included. Disability was evaluated before SCS and after 1, 3 and 12 months of HD-SCS. During the second, third and fourth visit, data from 130, 114 and 90 patients were available, respectively. HD-SCS resulted in a significant decrease in disability scores based on the analysis of observed data and with multiple imputations. The tipping point sensitivity analysis revealed that the shift parameter was 17. Thus, the conclusion concerning the time effect under a “missing at random” mechanism is robust when the shift parameter for the disability score is 17. From a clinical point of view, a shift of 17 points on disability is not very plausible. Therefore we tend to consider the conclusions drawn under “missing at random” as being robust.

The multidimensionality of chronic pain forces us to look beyond isolated assessment such as pain intensity, which does not consider multiple key parameters, particularly in post-operative Persistent Spinal Pain Syndrome (PSPS-T2) patients. Our ambition was to produce a novel Multi-dimensional Clinical Response Index (MCRI), including not only pain intensity but also functional capacity, anxiety-depression, quality of life and quantitative pain mapping, the objective being to achieve instantaneous assessment using machine learning techniques. Two hundred PSPS-T2 patients were enrolled in the real-life observational prospective PREDIBACK study with 12-month follow-up and received various treatments. From a multitude of questionnaires/scores, specific items were combined, as exploratory factor analyses helped to create a single composite MCRI; using pairwise correlations between measurements, it appeared to more accurately represent all pain dimensions than any previous classical score. It represented the best compromise among all existing indexes, showing the highest sensitivity/specificity related to Patient Global Impression of Change (PGIC). Novel composite indexes could help to refine pain assessment by informing the physician’s perception of patient condition on the basis of objective and holistic metrics, and also by providing new insights regarding therapy efficacy/patient outcome assessments, before ultimately being adapted to other pathologies.

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2) represents a main cause of work disruption. Beyond its societal consequences, occupational inactivity is responsible for a major decrease in physical/mental health in individuals but remains poorly analyzed. We designed a study to prospectively examine Professional Status (PS) evolution and its association with key bio-psychological markers. Data from 151 consecutively included working-age PSPS-T2 patients were analyzed to determine the proportion of professional inactivity and the relationships between PS and Social Gradient of Health (SGH), Numeric Pain Rating Scale (NPRS), EuroQol 5-Dimensional 5-Level (EQ-5D-5L), Oswestry Disability Index (ODI), Hospital Anxiety and Depression Scale (HADS), and Fear-Avoidance Belief Questionnaire work subscale (FABQ-W). Despite optimized medical management, 73.5% of PSPS-T2 patients remained inactive after 1 year of follow-up/p = 0.18. Inactive patients presented a low SGH/p = 0.002, higher NPRS/p = 0.048, lower EQ-5D-5L/p < 0.001, higher ODI/p = 0.018, higher HADS-D/p = 0.019 and higher FABQ-W/p < 0.001. No significant mediation effect of FABQ-W on SGH consequences regarding PS was observed in our structural model/p = 0.057. The link between unemployment and bio-psycho-social pain dimensions appears bidirectional and justifies intense collaboration with social workers. Optimizing therapeutical sequencing towards personalized professional plans implies restoring “Adapted Physical Function” as an initial goal, and tailoring an “Adapted Professional Activity”, matching with patient expectations and capabilities, as a final objective.

While Spinal Cord Stimulation (SCS) provides satisfaction to almost 2/3 of Persistent Spinal Pain Syndrome-Type 2 (PSPS-T2) patients implanted for refractory chronic back and/or leg pain, when not adequately addressed the back pain component, leaves patients in a therapeutic cul-de-sac. Peripheral Nerve field Stimulation (PNfS) has shown interesting results addressing back pain in the same population. Far from placing these two techniques in opposition, we suggest that these approaches could be combined to better treat PSPS-T2 patients. We designed a RCT (CUMPNS), with a 12-month follow-up, to assess the potential added value of PNfS, as a salvage therapy, in PSPS-T2 patients experiencing a “Failed SCS Syndrome” in the back pain component. Fourteen patients were included in this study and randomized into 2 groups (“SCS + PNfS” group/n = 6 vs. “SCS only” group/n = 8). The primary objective of the study was to compare the percentage of back pain surface decrease after 3 months, using a computerized interface to obtain quantitative pain mappings, combined with multi-dimensional SCS outcomes. Back pain surface decreased significantly greater for the ”SCS + PNfS” group (80.2% ± 21.3%) compared to the “SCS only” group (13.2% ± 94.8%) (p = 0.012), highlighting the clinical interest of SCS + PNfS, in cases where SCS fails to address back pain.

Despite the well-known clinical effects of spinal cord stimulation (SCS), the mechanisms of action have not yet been fully unraveled. The primary aim of this study was to measure whether electrochemical skin conductance, as a measure of peripheral sympathetic autonomic function, is altered by SCS. A second aim was to compare skin conductance levels of patients with failed back surgery syndrome (FBSS) with age- and sex-matched healthy controls. Twenty-three patients with FBSS treated with SCS participated in this study. Sudomotor function was measured with the SudoscanTM instrument on the hands and feet during SCS on and off states. Difference scores in skin conductance between patients and age- and sex-matched healthy controls were calculated. Normal sudomotor function at the painful lower limb was revealed for 61% of the patients when SCS was activated. Skin conductance levels were not altered between on and off states of SCS. Differences in scores between patients and healthy controls were significantly different from zero. This study showed that SCS does not influencing the sympathetic nervous system in patients with FBSS, as measured by skin conductance levels. Moreover, it suggested that there is no normalization of the functioning of the sympathetic nervous system, despite the effectiveness of SCS to reduce pain intensity.

Despite the established efficacy and effectiveness of Spinal Cord Stimulation (SCS), there is still no consensus on the supraspinal mechanisms of action of this therapy. The purpose of this study was to systematically review previously raised hypotheses concerning supraspinal mechanisms of action of SCS based on human, animal and computational studies. Searches were conducted using four electronic databases (PubMed, EMBASE, SCOPUS and Web of Science), backward reference searching and consultation with experts. The study protocol was registered prior to initiation of the review process (PROSPERO CRD42020161531). A total of 54 publications were included, 21 of which were animal studies, and 33 were human studies. The supraspinal hypotheses (n = 69) identified from the included studies could be categorized into six groups concerning the proposed supraspinal hypothesis, namely descending pathways (n = 24); ascending medial pathway (n = 13); ascending lateral pathway (n = 10); affective/motivational influences (n = 8); spinal–cerebral (thalamic)-loop (n = 3) and miscellaneous (n = 11). Scientific support is provided for the hypotheses identified. Modulation of the descending nociceptive inhibitory pathways, medial and lateral pathways were the most frequently reported hypotheses about the supraspinal mechanisms of action of SCS. These hypotheses were mainly supported by studies with a high or moderate confidence in the body of evidence.

The Social Gradient of Health (SGH), or position in the social hierarchy, is one of the major determinants of health. It influences the development and evolution of many chronic diseases. Chronic pain dramatically affects individual and social condition. Its medico-economic impact is significant and worldwide. Failed Back Surgery Syndrome or Persistent Spinal Pain Syndrome type 2 (PSPS-T2) represents one of its most fascinating and disabling conditions. However, the influence of SGH on PSPS-T2 has been poorly explored. We designed a prospective multicentric study (PREDIBACK study) to assess the SGH prevalence, and to examine its association with medical and psychological variables, in PSPS-T2 patients. This study included 200 patients to determine the SGH association with pain (NPRS), Quality of life (EQ-5D-5L), kinesiophobia (FABQ-Work), catastrophism (CSQ), and functional capacity (ODI). Around 85.3% of PSPS-T2 patients in our study had low SGH. Low SGH patients had a higher FABQ-Work and CSQ-Catastrophizing score than high SGH patients (p < 0.05). High SGH patients have a higher ODI score than low SGH patients (p < 0.10). Our results suggest that SGH is a relevant factor to guide prevention, research, and ultimately intervention in PSPS-T2 patients and could be more widely transposed to chronic pain.

The increased awareness of discrepancies between self-reporting outcome measurements and objective outcome measurements within the field of neuromodulation has accelerated the search towards more objective measurements. The aim of this study was to evaluate whether an electronic nose can differentiate between chronic pain patients in whom Spinal Cord Stimulation (SCS) was activated versus deactivated. Twenty-seven patients with Failed Back Surgery Syndrome (FBSS) participated in this prospective pilot study. Volatile organic compounds in exhaled breath were measured with electronic nose technology (Aeonose™) during SCS on and off states. Random forest was used with a leave-10%-out cross-validation method to determine accuracy of discriminating between SCS on and off states. Our random forest showed an accuracy of 0.56, with an area under the curve of 0.62, a sensitivity of 62% (95% CI: 41–79%) and a specificity of 50% (95% CI: 30–70%). Pain intensity scores were significantly different between both SCS states. Our findings indicate that we cannot discriminate between SCS off and on states based on exhaled breath with the Aeonose™ in patients with FBSS. In clinical practice, these findings imply that with a noninvasive electronic nose, exhaled breath cannot be used as an additional marker of the effect of neuromodulation.

BACKGROUND:Building on the recent finding that chronic pain patients with impaired functioning of the descending nociceptive inhibitory system (DNIS) present lower resting heart rate variability (HRV), this study aims to investigate the impact of Spinal Cord Stimulation (SCS) on HRV in patients with Failed Back Surgery Syndrome (FBSS). More precisely, we hypothesize that SCS influences the DNIS, with increased parasympathetic tone as a consequence, as measurable by HRV analysis. METHODS:Twenty-two patients diagnosed with FBSS and treated with SCS participated in this study. HRV was measured with a 2-lead ECG registration tool during on and off states of SCS. HRV analysis for time, frequency, time-frequency and nonlinear domain parameters was based on a 5-minute recording segment. RESULTS:The mean heart rate and low frequency power were significantly lower when SCS was activated. HRV, absolute and normalized high frequency power significantly increased during SCS compared to without SCS. The ratio of low frequency/high frequency ratios, as parameter for global sympathetic-parasympathetic equilibrium, significantly decreased when SCS was activated. CONCLUSIONS:When SCS is switched off, patients with FBSS present relatively stronger sympathetic tone and weaker parasympathetic activity. Activation of the SCS, possibly via stimulation of the DNIS, restores this disbalance of autonomic activity.

Despite the proven clinical value of spinal cord stimulation (SCS) for patients with failed back surgery syndrome (FBSS), factors related to a successful SCS outcome are not yet clearly understood. This study aimed to predict responders for high frequency SCS at 10 kHz (HF-10). Data before implantation and the last available data was extracted for 119 FBSS patients treated with HF-10 SCS. Correlations, logistic regression, linear discriminant analysis, classification and regression trees, random forest, bagging, and boosting were applied. Based on feature selection, trial pain relief, predominant pain location, and the number of previous surgeries were relevant factors for predicting pain relief. To predict responders with 50% pain relief, 58.33% accuracy was obtained with boosting, random forest and bagging. For predicting responders with 30% pain relief, 70.83% accuracy was obtained using logistic regression, linear discriminant analysis, boosting, and classification trees. For predicting pain medication decrease, accuracies above 80% were obtained using logistic regression and linear discriminant analysis. Several machine learning techniques were able to predict responders to HF-10 SCS with an acceptable accuracy. However, none of the techniques revealed a high accuracy. The inconsistent results regarding predictive factors in literature, combined with acceptable accuracy of the currently obtained models, might suggest that routinely collected baseline parameters from clinical practice are not sufficient to consistently predict the SCS response with a high accuracy in the long-term.

The Medication Quantification Scale III (MQS) is a tool to represent the negative impact of medication. A reduction in medication can serve as an indicator to evaluate treatment success. However, no cut-off value has yet been determined to evaluate whether a decrease in medication is clinically relevant. Therefore, the objective is to estimate the thresholds for the MQS and morphine milligram equivalents (MMEs) that best identify a clinically relevant important improvement for patients. Data from the Discover registry, in which patients with failed back surgery syndrome were treated with high-dose spinal cord stimulation, were used. Patient satisfaction was utilized to evaluate a clinically important outcome 12 months after stimulation. Anchor-based and distribution-based methods were applied to determine the minimal clinical important difference (MCID). Distribution-based methods revealed a value of 4.28 for the MQS and 33.61 for the MME as MCID. Anchor-based methods indicated a percentage change score of 41.2% for the MQS and 28.2% for the MME or an absolute change score of 4.72 for the MQS and 22.65 for the MME. For assessing a treatment outcome, we recommend using the percentage change score, which better reflects a clinically important outcome and is not severely influenced by high medication intake at baseline.

Patients with Failed Back Surgery Syndrome (FBSS) report a considerably lower health- related quality of life (HRQoL), compared to the general population. Spinal cord stimulation (SCS) is an effective treatment to offer pain relief in those patients. Despite initial treatment success of SCS, its effect sometimes wears off over time. This study investigates the added value of high dose SCS (HD-SCS) in patients with unsatisfactory conventional SCS, from a quality of life perspective. Seventy-eight FBSS patients who were treated with conventional SCS that failed to provide pain relief, were recruited in 15 centers. HRQoL was assessed before converting to HD-SCS (baseline) and three times after converting to HD-SCS using the EuroQol-5D-3L. Quality adjusted life years (QALY) were calculated and compared with conventional SCS. An overall significant increase over time was seen in utility values of the EQ5D-3L, as the mean value at baseline 0.283 (±0.21) increased to 0.452 (±0.29) at 12 months of HD-SCS. This average increase in utility coincides with an average increase of 0.153 (±0.24) QALY’s in comparison to continued conventional SCS. Besides the potential of HD-SCS to salvage patients with failed responses to conventional SCS, this treatment seems to be a more efficient treatment than conventional SCS.

Pain conditions are among the leading causes of global disability, impacting on global healthcare utilization (HCU). Health seeking behavior might be influenced by cognitive and emotional factors (CEF), which can be tackled by specific therapies. The purpose of this study was to systematically review the evidence concerning associations between CEF and HCU in people experiencing pain. Three databases were consulted: PubMed, Web of Science and EconLit. Risk of bias was assessed using the Downs and Black Checklist (modified). A total of 90 publications (total sample n = 59,719) was included after double-blind screening. In people experiencing pain, positive associations between general anxiety symptoms, depressive symptoms and catastrophizing and pain medication use were found. Additionally, there appears to be a relationship between general anxiety and depressive symptoms and opioid use. Symptom-related anxiety and psychological distress were found to be positively related with consulting behavior. Last, a positive association between use of complementary and alternative medicine and level of perceived symptom control was confirmed in people with pain. For other relationships no evidence or inconsistent findings were found, or they were insufficiently studied to draw firm conclusions, indicating that more research on this topic is needed.

Background: Patients with chronic fatigue syndrome (CFS) and chronic whiplash associated disorders (cWAD) present a reduced ability to activate central descending nociceptive inhibition after exercise, compared to measurements before exercise. It was hypothesised that a dysfunctional motor-induced inhibition of nociception partly explains this dysfunctional exercise-induced hypoalgesia. This study investigates if engagement of the motor system during movement preparation inhibits nociception-evoked brain responses in these patients as compared to healthy controls (HC). Methods: The experiment used laser-evoked potentials (LEPs) during three conditions (no task, mental task, movement preparation) while recording brain activity with a 32-channel electroencephalogram in 21 patients with cWAD, 20 patients with CFS and 18 HC. Two-factor mixed design Analysis of variance were used to evaluate differences in LEP amplitudes and latencies. Results: No differences in N1, N2, N2P2, and P2 LEP amplitudes were found between the HC, CFS, and cWAD groups. After nociceptive stimulation, N1, N2 (only at hand location), N2P2, and P2 LEP amplitudes significantly decreased during movement preparation compared to no task (within group differences). Conclusion: Movement preparation induces a similar attenuation of LEPs in patients with CFS, patients with cWAD and HC. These findings do not support reduced motor-induced nociceptive inhibition in these patients.