Multidimensional Analysis of Quality of Life in Patients with Chronic Non-Cancer Pain and Short- and Long-Term Intrathecal Analgesic Therapy.

Background: Intrathecal drug delivery (IDD) is part of the fourth analgesic step. Evidence on the quality of life of patients with refractory chronic non-cancer pain (CNCP) using these devices and their long-term outcomes is scarce. This study aims to evaluate patients with IDD to assess their HRQoL. Additionally, the study seeks to understand the patients' satisfaction with the treatment and changes in pain magnitude over time. Methods: Adult patients with CNCP and intrathecal drug delivery systems (IDDS) were included. The study population was divided into two groups: less than and more than 15 years of treatment. HRQoL was analyzed using validated questionnaires. Pain reduction was assessed using the visual analog scale (VAS), and treatment satisfaction was evaluated using the Patient Global Impression of Improvement scale. Results: The results indicate a poor HRQoL in IDD patients, with better scores in the group with ≥15 years of treatment. Pain reduction was similar in both groups, and patients reported a positive satisfaction level with the treatment. Conclusions: HRQoL in CNCP patients is severely affected. Long-term IDD patients have a similar or even better HRQoL in some respects compared to those with shorter follow-ups. IDD patients experienced pain reduction, with most feeling better or much better.

The CROM-VAS Test: A novel and reliable clinical test to assess immediate pain relief following treatment for movement-evoked neck pain.

BACKGROUND: The CROM-VAS Test is a novel method to quantify immediate hypoalgesic treatment effects for neck pain by measuring the reduction in pain intensity (using a VAS) at the same (sub)maximal neck position (using a CROM device) before and after treatment. It is a novel test designed to quantify immediate pain relief following treatment, without the potentially confounding effects of simultaneous improvements in function. OBJECTIVES: (1) To describe the CROM-VAS Test, (2) To assess reliability and absolute agreement of the CROM-VAS Test, and (3) To evaluate its distinctiveness by comparing it to changes in pressure pain threshold (PPT) and baseline pain scores. DESIGN: Cross-sectional study. METHODS: The CROM-VAS Test was assessed in 58 people with non-specific neck pain treated with cervical mobilisation and cervicothoracic manipulation. Inter-rater reliability (intraclass correlation coefficient (ICC1.1)) and absolute agreement (standard error of measurement (SEM), minimal detectable change (MDC) and Bland-Altman limits of agreement (LoA)) were determined. RESULTS: Reliability was high (ICC1.1: 0.91 (95%CI: 0.85-0.95) for the CROM-VAS Test in the painful direction and 0.73 (95%CI: 0.54-0.85) in the non/least painful direction). Agreement was good (CROM-VAS Test (painful direction): SEM: 2.3 mm; MDC: 6.4 mm; LoA: 13.5 to 16.6 mm; CROM-VAS Test (non/least painful direction): SEM: 4.0 mm; MDC: 11.1 mm; LoA: 14.7 to 22.0 mm). Low or negative correlations were observed between CROM-VAS Test scores and changes in PPT and baseline neck pain scores. CONCLUSION: The CROM-VAS Test has good clinimetric properties. It measures a distinct dimension of pain relief compared to PPTs and baseline pain scores.

Twelve-month results from a randomized controlled trial comparing differential target multiplexed spinal cord stimulation and conventional spinal cord stimulation in subjects with chronic refractory axial low back pain not eligible for spine surgery.

Background: Successful treatments for intractable chronic low back pain (CLBP) in patients who are not eligible for surgical interventions are scarce. The superior efficacy of differential target multiplexed spinal cord stimulation (DTM SCS) to conventional SCS (Conv-SCS) on the treatment of CLBP in patients with persistent spinal pain syndrome (PSPS) who have failed surgical interventions (PSPS-T2) motivated the evaluation of DTM SCS versus Conv-SCS on PSPS patients who are non-surgical candidates (PSPS-T1). Methods: This is a prospective, open label, crossover, post-market randomized controlled trial in 20 centers across the United States. Eligible patients were randomized to either DTM SCS or Conv-SCS in a 1:1 ratio. Primary endpoint was CLBP responder rate (percentage of subjects with ≥50% CLBP relief) at 3-month in randomized subjects who completed trialing (modified intention-to-treat population). Patients were followed up to 12 months. Secondary endpoints included change of CLBP and leg pain, responder rates, changes in disability, quality of life, patient satisfaction and global impression of change, and safety profile. An optional crossover was available at 6-month to all patients. Results: About 121 PSPS-T1 subjects with CLBP and leg pain mostly associated with degenerative disc disease and radiculopathy and who were not eligible for spine surgery were randomized. CLBP responder rate with DTM SCS (93.5%) was superior to Conv-SCS (36.4%) at the primary endpoint. Superior CLBP responder rates (88.1%-90.5%) were obtained with DTM SCS at all other timepoints. Mean CLBP reduction with DTM SCS (6.52 cm) was superior to that with Conv-SCS (3.01 cm) at the primary endpoint. Similar CLBP reductions (6.23-6.43 cm) were obtained with DTM SCS at other timepoints. DTM SCS provided significantly better leg pain reduction and responder rate, improvement of disability and quality of life, and better patient satisfaction and global impression of change. 90.9% of Conv-SCS subjects who crossed over were CLBP responders at completion of the study. Similar safety profiles were observed between the two groups. Conclusion: DTM SCS for chronic CLBP in nonsurgical candidates is superior to Conv-SCS. Improvements were sustained and provided significant benefits on the management of these patients.

The association between conditioned pain modulation and psychological factors in people with chronic spinal pain: A systematic review.

Chronic spinal pain has negative effects on physical and mental well-being. Psychological factors can influence pain tolerance. However, whether these factors influence descending modulatory control mechanisms measured by conditioned pain modulation (CPM) in people with chronic spinal pain is unclear. This systematic review investigated the association between CPM response and psychological factors in people with chronic spinal pain. Published and unpublished literature databases were searched from inception to 23rd October 2023 included MEDLINE, EMBASE, CINAHL, and PubMed. Studies assessing the association between CPM response and psychological factors in people with chronic spinal pain were eligible. Data were pooled through meta-analysis. Methodological quality was assessed using the AXIS tool and the certainty of evidence measured through GRADE. From 2172 records, seven studies (n = 598) were eligible. Quality of included studies was moderate. There was very low certainty of evidence that depression (r = 0.01 [95% CI -0.10 to 0.12], I2 = 0%), and anxiety (r = -0.20 [95% CI -0.56 to 0.16], I2 = 84%), fear avoidance (r = -0.10 [95% CI -0.30 to 0.10], I2 = 70%) had no statistical associations with CPM responder status. Higher pain catastrophising was associated with CPM non-responder status (r = -0.19; 95% CI: -0.37 to -0.02; n = 545; I2: 76%) based on a very low certainty of evidence measured by GRADE. There is currently limited available evidence demonstrating an association between CPM response and psychological factors for people with chronic pain. Managing an individual's chronic pain symptoms irrespective of comorbid psychological distress, should continue until evidence offer insights that more targeted interventions are needed.

Comparing Conventional Medical Management to Spinal Cord Stimulation for the Treatment of Low Back Pain in a Cohort of DISTINCT RCT Patients.

Aim: Low Back Pain (LBP) is a prevalent condition. Spinal cord stimulation (SCS) has emerged as a more effective, long-term treatment compared to conventional medical management (CMM). The DISTINCT study enrolled and randomized chronic LBP patients with no indication of traditional spine surgery. This analysis focuses comparing study outcomes on patients initially randomized to receive CMM treatment and subsequently crossed over to SCS after 6 months. Purpose: To compare the therapeutic effectiveness and cost-efficiency of passive recharge burst SCS to CMM. Patients and Methods: A total of 269 patients were enrolled with 162 randomly assigned to SCS and 107 to CMM. The DISTINCT study design allowed a crossover to the alternative treatment arm after 6 months. Patients underwent a trial and received a permanent implant if they reported ≥50% pain reduction. Outcome analysis included pain (NRS), disability (ODI), catastrophizing (PCS), quality of life (PROMIS-29) and health care utilization. Results: Seventy out of eighty-one patients opted to cross over to trial SCS at 6M with 94% (66/70) undergoing a trial. Among those, 88% (58/66) reported a ≥50% or more pain relief and 55 received a permanent implant. At 12M visit, 71.4% reported a ≥50% pain improvement sustained at the 18M visit, with 24.5% (12/49) indicating a ≥80% improvement. Disability reductions (79% meeting the minimally important difference of a 13-point decrease), decreased catastrophizing, and significant improvements in all PROMIS-29 domains were noted. Furthermore, 42% of the patients reported decreased or discontinued opioid usage. Clinical benefits at the 12M visit were sustained through the 18M visit accompanied by a significant reduction in healthcare utilization and a $1214 cost savings. Conclusion: SCS demonstrates superior, long-term performance and safety outcomes compared to CMM therapy in LBP patients who received both CMM and SCS therapy. Additionally, SCS patients experienced reduced healthcare resource utilization and lower costs compared to those receiving CMM.

Spinal Cord Stimulator Inequities Within the US Military Health System.

OBJECTIVES: Although studies have described inequities in spinal cord stimulation (SCS) receipt, there is a lack of information to inform system-level changes to support health care equity. This study evaluated whether Black patients exhaust more treatment options than do White patients, before receiving SCS. MATERIALS AND METHODS: This retrospective cohort study included claims data of Black and non-Latinx White patients who were active-duty service members or military retirees who received a persistent spinal pain syndrome (PSPS) diagnosis associated with back surgery within the US Military Health System, January 2017 to January 2020 (N = 8753). A generalized linear model examined predictors of SCS receipt within two years of diagnosis, including the interaction between race and number of pain-treatment types received. RESULTS: In the generalized linear model, Black patients (10.3% [8.7%, 12.0%]) were less likely to receive SCS than were White patients (13.6% [12.7%, 14.6%]) The interaction term was significant; White patients who received zero to three different types of treatments were more likely to receive SCS than were Black patients who received zero to three treatments, whereas Black and White patients who received >three treatments had similar likelihoods of receiving a SCS. CONCLUSIONS: In a health care system with intended universal access, White patients diagnosed with PSPS tried fewer treatment types before receiving SCS, whereas the number of treatment types tried was not significantly related to SCS receipt in Black patients. Overall, Black patients received SCS less often than did White patients. Findings indicate the need for structured referral pathways, provider evaluation on equity metrics, and top-down support.

Preoperative Counseling in Spinal Cord Stimulation: A Designated Driver in Implantable Pulse Generator-Related Inconveniences?

BACKGROUND: Spinal cord stimulation (SCS) has been reported to cause substantial pain relief and improved quality of life (QoL) in patients with persistent spinal pain syndrome (PSPS). Despite implantable pulse generator (IPG)-related inconveniences such as pain, shame, and discomfort affecting QoL and patient satisfaction, these are often neglected. Hence, the current study aims to determine the associations between patient satisfaction, IPG-related inconveniences, and preoperative counseling in a homogeneous group of patients with PSPS receiving SCS with IPG implantation in the gluteal or abdominal area. MATERIALS AND METHODS: Retrospective data on sample characteristics were gathered from the EPIC (electronic health record software) digital patient data base. Prospective data on patient satisfaction were obtained with a questionnaire that covered various topics such as shame, pain, disturbances in daily/intense activities, night rest and/or sleep, discomfort caused by clothing, and preoperative counseling. The exact location of the IPG and its scar were determined with photo analysis. Thereafter, the site of IPG placement was classified into separate quadrants within the gluteal and abdominal area. Patient satisfaction was defined as accepting the current location of the IPG without having the wish to undergo revision surgery. RESULTS: In total, 81 participants (50.9 ± 10 years) were included in this analysis, with patient satisfaction observed in 61 patients (75.3%). Among satisfied patients, more extensive preoperative counseling concerning IPG pain and discomfort was reported compared with patients who were not satisfied (p < 0.001). When comparing the two groups, significant differences were found in shame (8/81, 9.9%), IPG site pain (21/81, 25.9%), disturbance of activities (42/81, 51.9%), and clothing-related discomfort (42/81, 51.9%). CONCLUSIONS: On the basis of the current results, shared decision-making and comprehensive preoperative provision of information are recommended to optimize patient satisfaction regarding IPG pain, discomfort, and inconveniences. Although many patients experience these disadvantages despite successful SCS for pain related to PSPS, most of them accept this if they have received adequate preoperative information about expectations.

Exploring the Real-Time Variability and Complexity of Sitting Patterns in Office Workers with Non-Specific Chronic Spinal Pain and Pain-Free Individuals.

Chronic spinal pain (CSP) is a prevalent condition, and prolonged sitting at work can contribute to it. Ergonomic factors like this can cause changes in motor variability. Variability analysis is a useful method to measure changes in motor performance over time. When performing the same task multiple times, different performance patterns can be observed. This variability is intrinsic to all biological systems and is noticeable in human movement. This study aims to examine whether changes in movement variability and complexity during real-time office work are influenced by CSP. The hypothesis is that individuals with and without pain will have different responses to office work tasks. Six office workers without pain and ten with CSP participated in this study. Participant's trunk movements were recorded during work for an entire week. Linear and nonlinear measures of trunk kinematic displacement were used to assess movement variability and complexity. A mixed ANOVA was utilized to compare changes in movement variability and complexity between the two groups. The effects indicate that pain-free participants showed more complex and less predictable trunk movements with a lower degree of structure and variability when compared to the participants suffering from CSP. The differences were particularly noticeable in fine movements.

Clinical Impact of Thermotherapy and Spinal Twisting Massage on Chronic Non-Specific Spinal Pain.

As the prevalence of chronic non-specific spinal pain rises, the utilization of diverse massage devices for therapeutic intervention increases rapidly. However, research on their mechanisms, particularly those involving spinal twisting, is limited. This study was designed to evaluate the impact of heat application and spinal twisting massage techniques on individuals suffering from chronic non-specific spinal pain. A total of 36 individuals were divided into two groups: a control group (18 participants) and an experimental group (18 participants). The experimental group received heat treatment plus spinal twisting massage twice a week for four weeks, while the control group received heat therapy plus traditional vibration massage techniques. Effectiveness was measured using the Visual Analog Scale (VAS), the Pressure Pain Threshold (PPT), the Korean Western Ontario and McMaster Universities (K-WOMAC) Index, spine tilt, and Cobb angle. VAS, K-WOMAC, and PPT significantly improved in both groups at all three time points. VAS notably decreased in the experimental group compared to the control group (p-value: 0.0369). Despite improvements in K-WOMAC and PPT scores within the experimental group, statistical significance remained elusive. Furthermore, spine tilt and Cobb angle showed no significant differences from baseline to the 6th week. In conclusion, the application of thermotherapy coupled with twisting massage demonstrates significant efficacy in mitigating chronic non-specific spinal pain, surpassing the pain-relief outcomes achieved through heat therapy in combination with standard vibration massage techniques.

Exercise as an anti-inflammatory Therapy in Axial Spondyloarthritis Therapeutic Intervention (EXTASI) study: a randomized controlled trial.

Objectives: Axial SpA (axSpA) is a chronic inflammatory disease, yet despite known anti-inflammatory effects of exercise, the effect of exercise on inflammatory immune cell populations and associated inflammatory profiles in axSpA is unknown. This randomized controlled trial investigated the effect of 12 weeks of walking on symptom severity, cardiometabolic health, inflammatory biomarkers and immune cell populations. Methods: Twenty people (60% male) living with axSpA who were on a stable dose of NSAIDs participated. Participants were randomly assigned to control or exercise (30 min of walking five times per week). Participants were invited back every 4 weeks for assessment. Results: There was a 0% dropout rate and no adverse events in the exercise group, showing walking exercise was well tolerated. Home-based walking for 12 weeks lowered the proportion of pro-inflammatory monocytes, whereas they increased in the control group. Changes were associated with lower IL-6 and CRP concentrations, lower spinal pain and lower systolic blood pressure in the exercise group, whereas these markers increased in the control group. Reductions in IL-6 and pro-inflammatory monocytes with exercise were independent of lower body fat percentage. Conclusions: Supplementing NSAID therapy with walking exercise can improve inflammatory immune profiles in people with axSpA, coinciding with reductions in spinal pain. Importantly, the exercise was well tolerated, suggesting walking exercise can be used as an adjuvant anti-inflammatory therapy for NSAID treatments. This should now be explored in people living with axSpA who have had high enough disease activity to necessitate the prescription of biologic or synthetic DMARD treatments. Trial registration: ClinicalTrials.gov (http://clinicaltrials.gov), NCT04368494.

Rapid and Sustained Effect of Ixekizumab on Patient Global, Spinal Pain, Stiffness, and Fatigue in Chinese Patients with Radiographic Axial Spondyloarthritis.

INTRODUCTION: Ixekizumab, an interleukin 17A (IL-17A) inhibitor, has demonstrated rapid and sustained improvement in the signs and symptoms in patients with active radiographic axial spondyloarthritis (r-axSpA) in global and Chinese populations. We studied the effect of ixekizumab on patient-reported outcomes (PROs) (including patient global, spinal pain, stiffness, and fatigue) and overall health-related quality of life (HRQoL) of ixekizumab in the phase 3 study in China. METHODS: In this Chinese phase 3, randomized, double-blind, placebo-controlled study, patients with r-axSpA were randomized (1:1) to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg) or placebo for 16 weeks. At week 16, patients receiving placebo were switched to IXEQ4W, and those receiving IXEQ4W continued, until week 52. Data for patient global, spinal pain, spinal pain at night, stiffness, and fatigue were collected through week 52. Minimally clinical important differences (MCIDs) were determined for spinal pain and spinal pain at night. The subgroup analyses by baseline disease duration since diagnosis and baseline C-reactive protein (CRP) level were conducted post hoc. RESULTS: Compared with placebo, patients treated with IXEQ4W reported significantly greater improvement with a rapid onset in changes from baseline of PROs (patient global, spinal pain, spinal pain at night, stiffness, and fatigue) through week 16. Improvements were maintained through week 52. A similar trend of improvement was also observed in MCID response in spinal pain and spinal pain at night. The improvement in overall HRQoL was supported by EQ-5D-5L assessment. Subgroup analyses demonstrated that IXEQ4W provided significantly greater efficacy at week 16 compared with placebo, irrespective of baseline disease duration or baseline CRP level. CONCLUSION: IXEQ4W provided rapid and sustained improvement in clinically relevant PROs and overall HRQoL through 1-year treatment in Chinese patients with r-axSpA. Regardless of the baseline disease duration or baseline CRP level, consistent efficacy was observed. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04285229.

Synergistic neuromodulation therapy for persistent spinal pain: a proof-of-concept trial on the use of spinal cord and dorsal root ganglion stimulation.

PURPOSE: Persistent Spinal Pain Syndrome type 2 (PSPS-T2) poses a significant clinical challenge, demanding innovative therapeutic interventions. The integration of Spinal Cord Stimulation (SCS) and Dorsal Root Ganglion Stimulation (DRG-S) is emerging as a potent synergistic strategy for comprehensive pain management. This single patient-blind proof of concept (POC) trial explores the efficacy and synergistic potential of combined SCS and DRG-S in a patient with refractory PSPS-T2. METHODS: A 45-year-old male with intractable PSPS-T2 underwent a unique, methodically structured study, involving three treatment phases: Phase A with SCS alone, Phase B with DRG-S alone, and Phase C The patient, blinded to the treatment modalities, provided pain assessments using the Visual Analogue Scale (VAS) and Douleur Neuropathique 4 Questions (DN4) conducted by clinical investigators at each phase. Baseline pain scores were ten and nine, respectively. RESULTS: Distinct responses were noted across the phases. Phase A demonstrated moderate pain relief, while Phase B offered further pain intensity reduction. However, Phase C, combining both strategies, yielded the most significant improvement, remarkably enhancing the patient's quality of life and functional capacity. CONCLUSION: This POC trial underscores the synergistic potential of SCS and DRG-S in managing complex cases of PSPS-T2, suggesting a paradigm shift towards integrated neuromodulation strategies for enhanced pain control. The development of dual intent implantable pulse generators (IPGs) capable of offering combination therapy simultaneously might be effective for pain management in select cases. The significant pain reduction and functional improvement observed advocate for further research in dual neuromodulation therapies. TRIAL REGISTRATION NUMBER: IRB 20190536.

Differences between the healthcare systems of Quebec and France for the treatment of pain due to spinal disorders.

In Quebec, Canada, the public healthcare system offers free medical services. However, patients with spinal pain often encounter long waiting times for specialist appointments and limited physiotherapy coverage. In contrast, private clinics provide expedited care but are relatively scarce and entail out-of-pocket expenses. Once a patient with pain caused by a spinal disorder meets a pain medicine specialist, spinal intervention is quickly performed when indicated, and patients are provided lifestyle advice. Transforaminal epidural steroid injections are frequently administered to patients with radicular pain, and steroid injections are administered on a facet joint to control low back or neck pain. Additionally, medial branch blocks are performed prior to thermocoagulation. France's universal healthcare system ensures accessibility at controlled costs. It emphasizes physical activity and provides free physical therapy services. However, certain interventions, such as transforaminal and interlaminar epidural injections, are not routinely used in France owing to limited therapeutic efficacy and safety concerns. This underutilization may be a potential cause of chronic pain for many patients. By examining the differences, strengths, and weaknesses of these two systems, valuable insights can be gained for the enhancement of global spinal pain management strategies, ultimately leading to improved patient outcomes and satisfaction.

Genetically predicted causal effects of gut microbiota on spinal pain: a two-sample Mendelian randomization analysis.

Background: Observational studies have hinted at a correlation between the gut microbiota and spinal pain (SP). However, the impact of the gut microbiota on SP remains inconclusive. Methods: In this study, we employed a two-sample Mendelian randomization (MR) analysis to explore the causal relationship between the gut microbiota and SP, encompassing neck pain (NP), thoracic spine pain (TSP), low back pain (LBP), and back pain (BP). The compiled gut microbiota data originated from a genome-wide association study (GWAS) conducted by the MiBioGen consortium (n = 18,340). Summary data for NP were sourced from the UK Biobank, TSP from the FinnGen Biobank, and LBP from both the UK Biobank and FinnGen Biobank. Summary data for BP were obtained from the UK Biobank. The primary analytical approach for assessing causal relationships was the Inverse Variance Weighted (IVW) method, supplemented by various sensitivity analyses to ensure result robustness. Results: The IVW analysis unveiled 37 bacterial genera with a potential causal relationship to SP. After Benjamini-Hochberg corrected test, four bacterial genera emerged with a strong causal relationship to SP. Specifically, Oxalobacter (OR: 1.143, 95% CI 1.061-1.232, P = 0.0004) and Tyzzerella 3 (OR: 1.145, 95% CI 1.059-1.238, P = 0.0007) were identified as risk factors for LBP, while Ruminococcaceae UCG011 (OR: 0.859, 95% CI 0.791-0.932, P = 0.0003) was marked as a protective factor for LBP, and Olsenella (OR: 0.893, 95% CI 0.839-0.951, P = 0.0004) was recognized as a protective factor for low back pain or/and sciatica. No significant heterogeneity or horizontal pleiotropy was observed through alternative testing methods. Conclusion: This study establishes a causal relationship between the gut microbiota and SP, shedding light on the "gut-spine" axis. These findings offer novel perspectives for understanding the etiology of SP and provide a theoretical foundation for potential interventions targeting the gut microbiota to prevent and treat SP.

Clinical Patient-Relevant Outcome Domains for Persistent Spinal Pain Syndrome-A Scoping Review and Expert Panels.

Large variation exists in the monitoring of clinical outcome domains in patients with persistent spinal pain syndrome (PSPS). Furthermore, it is unclear which outcome domains are important from the PSPS patient's perspective. The study objectives were to identify patient-relevant outcome domains for PSPS and to establish a PSPS outcomes framework. PubMed, CINAHL, Cochrane, and EMBASE were searched to identify studies reporting views or preferences of PSPS patients on outcome domains. The Arksey and O'Malley framework was followed to identify outcome domains. An expert panel rated the domains based on the importance for PSPS patients they have treated. A framework of relevant outcome domains was established using the selected outcome domains by the expert panel. No studies were found for PSPS type 1. Five studies with 77 PSPS type 2 patients were included for further analysis. Fourteen outcome domains were identified. An expert panel, including 27 clinical experts, reached consensus on the domains pain, daily activities, perspective of life, social participation, mobility, mood, self-reliance, and sleep. Eleven domains were included in the PSPS type 2 outcomes framework. This framework is illustrative of a more holistic perspective and should be used to improve the evaluation of care for PSPS type 2 patients. Further research is needed on the prioritization of relevant outcome domains.

Distinct Functional Connectivity Patterns for Intermittent Vs Constant Neuropathic Pain Phenotypes in Persistent Spinal Pain Syndrome Type 2 Patients.

Background: Chronic low back pain (cLBP) has been associated with alterations in brain functional connectivity (FC) but based upon heterogeneous populations and single network analyses. Our goal is to study a more homogeneous cLBP population and focus on multiple cross-network (CN) connectivity analysis. We hypothesize that within this population: 1) altered CN FC, involving emotion and reward/aversion functions are related to their pain levels and 2) altered relationships are dependent upon pain phenotype (constant neuropathic vs intermittent pain). Methods: In this case series, resting state fcMRI scans were obtained over a study duration of 60 months from 23 patients (13 constant neuropathic and 10 intermittent pain) with Persistent Spinal Pain Syndrome (PSPS Type 2) being considered for spinal cord stimulation (SCS) therapy at a single academic center. Images were acquired using a Discovery MR750 GE scanner. During the resting state acquisitions, they were asked to close their eyes and relax. The CN analysis was performed on 7 brain networks and compared to age-matched controls. Linear regression was used to test the correlation between CN connectivity and pain scores. Results: CN FC involving emotion networks (STM: striatum network index) was significantly lower than controls in all patients, regardless of pain phenotype (P < 0.003). Pain levels were positively correlated with emotional FC for intermittent pain but negatively correlated for constant pain. Conclusion: This is the first report of 1) altered CN FC involving emotion/reward brain circuitry in 2) a homogeneous population of cLBP patients with 3) two different pain phenotypes (constant vs intermittent) in PSPS Type 2 patients being considered for SCS. FC patterns were altered in cLBP patients as compared to controls and were characteristic for each pain phenotype. These data support fcMRI as a potential and objective tool in assessing pain levels in cLBP patients with different pain phenotypes.

Emotion Regulation and Psychological Dependence on Pain Medication among Hospital Outpatients with Chronic Spinal Pain: The Influence of Rumination about Pain and Alexithymia.

Objective: To examine the extent to which pain acceptance, pain catastrophising and alexithymia moderate associations between pain intensity and psychological pain medication dependence. Methods: Participants (106 hospital outpatients with chronic spinal pain) completed the Leeds Dependence Questionnaire (LDQ) to measure psychological dependence on pain medication, and the Chronic Pain Acceptance Questionnaire-8 (CPAQ-8), the Pain Catastrophising Scale (PCS) and the Toronto Alexithymia Scale-20 (TAS-20), plus the Depression, Anxiety and Stress Scale-21 (DASS-21). Results: Multiple linear regression showed that degree of psychological dependence (measured dimensionally across the range of LDQ scores) was associated with TAS subscale difficulty identifying feelings (DIF) (ß = 0.249, p = <0.002) and PCS subscale rumination (ß = 0.193, p = 0.030), independently of pain intensity and risk behaviors for medication misuse. The effect of pain intensity was moderated by rumination, with pain intensity more strongly associated with dependence when rumination was high (interaction ß = 0.192, p = 0.004). Logistic regression showed that the effect of pain intensity on severe dependence (measured categorically as LDQ score ≥ 20) was moderated by alexithymia, so that severe dependence was independently associated with the combination of intense pain and high alexithymia (interaction odds ratio = 7.26, 95% CIs = 1.63-32.42, p = 0.009). Conclusions: Rumination and alexithymia moderated the associations between pain intensity and psychological pain medication dependence, consistent with emotion regulation theory. This raises the possibility that specifically targeting rumination about pain and symptoms of alexithymia could potentially improve the effectiveness of psychological interventions for chronic pain and help people to avoid or reduce their psychological dependence on pain medication.

Catheter Tip-Associated Mass With Continuous Infusion of Sufentanil for Persistent Spinal Pain Syndrome Type 2: A Case Report Including Histopathologic Examination and Review of the Associated Basic and Clinical Research.

OBJECTIVES: Intrathecal opioids delivered by implanted pumps are used to treat malignant or nonmalignant chronic pain. In this study, we 1) review a case in which intrathecal infusions of sufentanil along with other adjuvants were used and after an extended period led to an intrathecal mass and 2) compared and contrasted the potential mechanisms for these phenomena. MATERIALS AND METHODS: A woman aged 66 years with a history of scoliosis and multiple spine surgeries was treated with an implantable drug delivery system for treating persistent pain after laminectomy. The patient received intrathecal medication comprising sufentanil, bupivacaine, and clonidine. RESULTS: Intrathecal therapy over approximately ten years served to reduce pain and improve function over the treatment period. After the extended treatment interval, the patient developed an intrathecal mass that was associated with impairment. The mass was surgically removed. Systematic histopathology revealed the space-occupying mass to largely comprise fibroblasts and some inflammatory cells embedded in a collagen mass located proximally to the catheter tip. CONCLUSIONS: To our knowledge, this is the first published case report of sufentanil causing this complication. The science and mechanism of intrathecal catheter tip-associated mass formation and associated clinical research correlates are reviewed in detail, and explanations for this phenomenon are proposed based on histochemical analysis of the patient's pathology findings.

Virtual Reality Therapy for the Management of Chronic Spinal Pain: Systematic Review and Meta-Analysis.

BACKGROUND: The effectiveness of virtual reality (VR) therapy in adults with chronic spinal pain (CSP) is unclear. OBJECTIVE: This study was conducted to compare the effectiveness of VR therapy and other therapies in adults with CSP, especially patients with inflammation-related pain. METHODS: PubMed, Web of Science, Cochrane Library, Embase, and CINAHL databases were searched up to November 11, 2023. Randomized controlled trials (RCTs) comparing adults with CSP receiving VR therapy with those receiving other therapies were included. The trial registration platform as well as the reference lists of included studies and previous systematic reviews and meta-analyses were manually searched. Two independent reviewers performed study selection, data extraction, risk-of-bias assessment, and evaluation of the quality of the evidence. The weighted mean difference (WMD) was used as the effect size used to synthesize the outcome measure. RESULTS: In total, 16 RCTs involving 800 participants were included in this meta-analysis. The pooled data from 15 (94%) RCTs including 776 (97%) participants showed that VR therapy was superior in improving pain intensity (WMD=-1.63, 95% CI -2.11 to -1.16, P<.001, I2=90%) and reducing inflammatory markers, including C-reactive protein (WMD=-0.89, 95% CI -1.07 to -0.70, P<.001, I2=0%), tumor necrosis factor-alpha (WMD=-6.60, 95% CI -8.56 to -4.64, P<.001, I2=98%), and interleukin-6 (WMD=-2.76, 95% CI -2.98 to -2.53, P<.001, I2=0%). However, no significant differences were found in terms of the spinal range of motion (ROM), disability level, or fear of movement. In addition, 10 (63%) of the included RCTs had a high risk of bias. CONCLUSIONS: VR therapy may be an effective and safe intervention for reducing symptoms in patients with CSP, as it is shown to exert significant analgesic effects and beneficial improvements in inflammatory factor levels. However, this approach may not have significant effects on the spinal ROM, disability level, or fear of movement. Notably, the quality of the evidence from the RCTs included in this study ranged from moderate to low. Therefore, we recommend that readers interpret the results of this study with caution. TRIAL REGISTRATION: PROSPERO CRD42022382331; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=382331.