Giovanna Laura Neves Antonio Gaban, Jonas Bloch Thorlund, Kristian Kjær-Staal Petersen, Thomas Graven-Nielsen, Pia Schou, Henrik Bjarke Vægter
Background
Central modulatory pain mechanisms may influence improvements after exercise in low back pain (LBP). This observational study explored whether temporal summation of pain (TSP) and exercise-induced hypoalgesia (EIH) are associated with improvements in resting pain and movement-evoked pain, as it may improve the understanding of variation in effectiveness after an exercise program in individuals with LBP.
Methods
At baseline and after an 8-week exercise program, ratings of resting pain and movement-evoked pain on a 0–10 numerical rating scale (NRS) were assessed in 69 individuals with LBP. Cuff algometry at the lower leg (recording of the pain intensity to 10 repeated painful cuff stimulation) and pressure pain thresholds at the low back and leg immediately before and after a 6-min walking test were used to assess baseline TSP and EIH, respectively. Linear regression analyses adjusted for age and gender were used to assess the strength and direction of associations between baseline TSP and EIH with pain improvements (baseline minus Week 8).
Results
Resting-pain NRS scores were reduced by 0.9 (0.5–1.3) and movement-evoked pain by 0.9 (0.4–1.5) after 8 weeks of exercise. Higher baseline TSP was associated with improvement in resting pain (B = 0.29, p = 0.014), but not significantly with improvement in movement-evoked pain. Baseline EIH, regardless of the site point, was not significantly associated with resting or movement-evoked pain improvements.
Conclusion
This study suggests that higher TSP at baseline is weakly but significantly associated with larger improvement in resting-pain intensity after an 8-week exercise program in people with LBP but this should be confirmed in larger studies.
Significance Statement
Assessing central pain mechanisms may help identify individuals more likely to benefit from therapy, guiding personalised exercise-based treatments. Thus, this exploratory study provides preliminary evidence that higher baseline TSP is associated with greater improvements in resting pain following an exercise intervention. However, neither TSP nor EIH were associated with movement-evoked pain changes. These findings highlight the potential clinical relevance of evaluating central pain mechanisms when designing rehabilitation strategies for pain relief in LBP.
背景：中枢调节疼痛机制可能影响运动后腰痛（LBP）的改善。这项观察性研究探讨了疼痛的时间累积（TSP）和运动诱发的痛觉减退（EIH）是否与静息疼痛和运动诱发的疼痛的改善有关，因为它可以提高对LBP患者运动计划后有效性变化的理解。方法：在基线和8周运动计划后，对69名腰痛患者的静息疼痛和运动诱发疼痛进行0-10数值评定量表（NRS）评分。分别采用下肢袖带测量法（记录疼痛强度至10次重复疼痛袖带刺激）和6分钟步行试验前后腰背部和腿部的压力痛阈值来评估基线TSP和EIH。采用调整了年龄和性别的线性回归分析来评估基线TSP和EIH与疼痛改善（基线减去第8周）之间关联的强度和方向。结果：运动8周后，静息痛NRS评分降低0.9(0.5 ~ 1.3)，运动诱发痛评分降低0.9（0.4 ~ 1.5）。较高的基线TSP与静息疼痛的改善相关（B = 0.29, p = 0.014），但与运动诱发疼痛的改善无显著关系。基线EIH，无论在哪个部位，与静息或运动诱发的疼痛改善没有显著相关。结论：本研究表明，基线时较高的TSP与腰痛患者进行8周运动后静息疼痛强度的改善有微弱但显著的相关性，但这需要在更大规模的研究中得到证实。意义声明：评估中枢性疼痛机制可能有助于识别更有可能从治疗中受益的个体，指导个性化的基于运动的治疗。因此，这项探索性研究提供了初步证据，表明运动干预后，较高的基线TSP与静息疼痛的改善有关。然而，TSP和EIH均与运动引起的疼痛变化无关。这些发现强调了在设计缓解腰痛的康复策略时评估中枢性疼痛机制的潜在临床意义。
{"title":"Baseline Pain Summation Predicts Resting but Not Movement Pain Relief After Exercise in Low Back Pain","authors":"Giovanna Laura Neves Antonio Gaban, Jonas Bloch Thorlund, Kristian Kjær-Staal Petersen, Thomas Graven-Nielsen, Pia Schou, Henrik Bjarke Vægter","doi":"10.1002/ejp.70164","DOIUrl":"10.1002/ejp.70164","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Central modulatory pain mechanisms may influence improvements after exercise in low back pain (LBP). This observational study explored whether temporal summation of pain (TSP) and exercise-induced hypoalgesia (EIH) are associated with improvements in resting pain and movement-evoked pain, as it may improve the understanding of variation in effectiveness after an exercise program in individuals with LBP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>At baseline and after an 8-week exercise program, ratings of resting pain and movement-evoked pain on a 0–10 numerical rating scale (NRS) were assessed in 69 individuals with LBP. Cuff algometry at the lower leg (recording of the pain intensity to 10 repeated painful cuff stimulation) and pressure pain thresholds at the low back and leg immediately before and after a 6-min walking test were used to assess baseline TSP and EIH, respectively. Linear regression analyses adjusted for age and gender were used to assess the strength and direction of associations between baseline TSP and EIH with pain improvements (baseline minus Week 8).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Resting-pain NRS scores were reduced by 0.9 (0.5–1.3) and movement-evoked pain by 0.9 (0.4–1.5) after 8 weeks of exercise. Higher baseline TSP was associated with improvement in resting pain (<i>B</i> = 0.29, <i>p</i> = 0.014), but not significantly with improvement in movement-evoked pain. Baseline EIH, regardless of the site point, was not significantly associated with resting or movement-evoked pain improvements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study suggests that higher TSP at baseline is weakly but significantly associated with larger improvement in resting-pain intensity after an 8-week exercise program in people with LBP but this should be confirmed in larger studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>Assessing central pain mechanisms may help identify individuals more likely to benefit from therapy, guiding personalised exercise-based treatments. Thus, this exploratory study provides preliminary evidence that higher baseline TSP is associated with greater improvements in resting pain following an exercise intervention. However, neither TSP nor EIH were associated with movement-evoked pain changes. These findings highlight the potential clinical relevance of evaluating central pain mechanisms when designing rehabilitation strategies for pain relief in LBP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"29 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna M. Dückelmann, Roman Rolke, Katharina Möller, Walter Magerl, Sylvia Mechsner, Andreas Kopf
Background
Endometriosis is a chronic, inflammatory disease with considerable symptom load in affected female patients. Cyclic pain (associated with menstruation) dominates in most patients, but few patients suffer from persistent non-cyclic pain. This study aims to investigate whether the somatosensory profile in endometriosis differs from healthy controls or between cyclic and non-cyclic subtypes. Moreover, we aimed at potential identifiers of peripheral or central nervous sensitization underpinnings of endometriosis in the QST profile.
Methods
The standardised investigation protocol for quantitative sensory testing (QST) of the German research network of neuropathic pain was used to find possible differences compared to healthy controls or between cyclic and non-cyclic subtypes of endometriosis potentially providing hints for altered peripheral and central nociceptive processing.
Results
Endometriosis patients showed significant hyperalgesia to cold and blunt pressure in the affected body area (non-cyclic>cyclic, all p < 0.05), but not pinprick hyperalgesia, dynamic mechanical allodynia or facilitated pain summation (all p > 0.30). Exaggerated pressure hyperalgesia was most pronounced, regionally restricted and present in every patient (p << 0.0001). Higher thermal and tactile detection thresholds indicated non-nociceptive somatosensory loss, which differed only marginally between subgroups. Thermal loss and hyperalgesia to cold, heat and blunt pressure were also identified to a lesser extent in a remote test site (hand dorsum).
Conclusions
Endometriosis patients exhibited a pattern of somatosensory changes that is consistent with peripheral rather than central sensitization. Primary afferent sensitization facilitating spinal transmission of convergent input from the affected and suprapubic referred pain area is the most likely mechanism of hyperalgesia in endometriosis.
Significance Statement
Pain and hyperalgesia are amongst the most burdensome features in endometriosis. This QST case–control study in endometriosis patients identifies massive pressure hyperalgesia as the most significant somatosensory alteration in the viscerotome of the lower abdomen, which is easily accessible for testing in patients. This finding highlights the role of peripheral sensitization as the dominant mechanism of endometriosis-related hyperalgesia, which
{"title":"Quantitative Sensory Testing in Endometriosis Patients With Cyclic vs. Non-Cyclic Pain—A Case–Control Study","authors":"Anna M. Dückelmann, Roman Rolke, Katharina Möller, Walter Magerl, Sylvia Mechsner, Andreas Kopf","doi":"10.1002/ejp.70163","DOIUrl":"10.1002/ejp.70163","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Endometriosis is a chronic, inflammatory disease with considerable symptom load in affected female patients. Cyclic pain (associated with menstruation) dominates in most patients, but few patients suffer from persistent non-cyclic pain. This study aims to investigate whether the somatosensory profile in endometriosis differs from healthy controls or between cyclic and non-cyclic subtypes. Moreover, we aimed at potential identifiers of peripheral or central nervous sensitization underpinnings of endometriosis in the QST profile.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The standardised investigation protocol for quantitative sensory testing (QST) of the German research network of neuropathic pain was used to find possible differences compared to healthy controls or between cyclic and non-cyclic subtypes of endometriosis potentially providing hints for altered peripheral and central nociceptive processing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Endometriosis patients showed significant hyperalgesia to cold and blunt pressure in the affected body area (non-cyclic>cyclic, all <i>p</i> < 0.05), but not pinprick hyperalgesia, dynamic mechanical allodynia or facilitated pain summation (all <i>p</i> > 0.30). Exaggerated pressure hyperalgesia was most pronounced, regionally restricted and present in every patient (<i>p</i> << 0.0001). Higher thermal and tactile detection thresholds indicated non-nociceptive somatosensory loss, which differed only marginally between subgroups. Thermal loss and hyperalgesia to cold, heat and blunt pressure were also identified to a lesser extent in a remote test site (hand dorsum).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Endometriosis patients exhibited a pattern of somatosensory changes that is consistent with peripheral rather than central sensitization. Primary afferent sensitization facilitating spinal transmission of convergent input from the affected and suprapubic referred pain area is the most likely mechanism of hyperalgesia in endometriosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>Pain and hyperalgesia are amongst the most burdensome features in endometriosis. This QST case–control study in endometriosis patients identifies massive pressure hyperalgesia as the most significant somatosensory alteration in the viscerotome of the lower abdomen, which is easily accessible for testing in patients. This finding highlights the role of peripheral sensitization as the dominant mechanism of endometriosis-related hyperalgesia, which ","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"29 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karsten L. Lassen, Kristian Hermander, Pether Jildenstål, Nanna Wagner, Annelie Augustinsson, Carina Sjöberg, Anja Geisler
Background and Objective
Virtual reality (VR) is a rapidly evolving technology that is currently utilized in hospital settings for various types of surgical procedures. The extent to which VR is evident in improving patient outcomes is unknown. This systematic review assesses the impact of VR on adult patients undergoing elective surgical procedures.
Databases and Data Treatment
The following databases were sought: CENTRAL, MEDLINE, EMBASE, and CINAHL. All studies published after 2017 were included. The risk of bias was assessed using the ROB2 and ROBINS-I. Meta-analyses and Trial Sequential Analyses were performed, and the quality of evidence was evaluated using the GRADE approach for the randomised controlled trials.
Results
A total of 37 full-text studies (n = 3152) were included. VR significantly reduced anxiety measured by the Numeric Rating Scale (p < 0.0001) and the State–Trait Anxiety Inventory (p = 0.008). Furthermore, Numeric Rating Scale pain was significantly reduced (p < 0.00005), with a significantly shorter recovery time and a non-significant improvement in patient satisfaction. Adverse events were infrequent and mild, with no serious adverse events reported. The risk of bias was primarily “some concerns”, and the certainty of evidence ranged from moderate to low.
Conclusions
VR appears effective in reducing pain and anxiety in adult patients in an in-hospital setting. It offers a relatively safe adjunct to standard care with minimal side effects. However, heterogeneity in outcomes and the risk of bias suggest a need for more standardised, high-quality trials.
Significance Statement
This systematic review with meta-analysis and trial sequential analysis provides updated evidence that virtual reality can significantly reduce anxiety and pain in patients undergoing surgical procedures. Through combining recent RCTs and cohort studies with robust methodological approaches, this review strengthens the evidence for VR as an effective non-pharmacological intervention. With minimal adverse events and significant improvements in recovery time, VR represents a scalable tool that can strengthen multimodal strategies and promote safer and more comfortable patient experiences.
{"title":"Virtual Reality Is Safe and Can Reduce In-Hospital Anxiety and Pain: A Systematic Review With Meta-Analyses and Trial Sequence Analyses","authors":"Karsten L. Lassen, Kristian Hermander, Pether Jildenstål, Nanna Wagner, Annelie Augustinsson, Carina Sjöberg, Anja Geisler","doi":"10.1002/ejp.70165","DOIUrl":"10.1002/ejp.70165","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objective</h3>\u0000 \u0000 <p>Virtual reality (VR) is a rapidly evolving technology that is currently utilized in hospital settings for various types of surgical procedures. The extent to which VR is evident in improving patient outcomes is unknown. This systematic review assesses the impact of VR on adult patients undergoing elective surgical procedures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Databases and Data Treatment</h3>\u0000 \u0000 <p>The following databases were sought: CENTRAL, MEDLINE, EMBASE, and CINAHL. All studies published after 2017 were included. The risk of bias was assessed using the ROB2 and ROBINS-I. Meta-analyses and Trial Sequential Analyses were performed, and the quality of evidence was evaluated using the GRADE approach for the randomised controlled trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 37 full-text studies (<i>n</i> = 3152) were included. VR significantly reduced anxiety measured by the Numeric Rating Scale (<i>p</i> < 0.0001) and the State–Trait Anxiety Inventory (<i>p</i> = 0.008). Furthermore, Numeric Rating Scale pain was significantly reduced (<i>p</i> < 0.00005), with a significantly shorter recovery time and a non-significant improvement in patient satisfaction. Adverse events were infrequent and mild, with no serious adverse events reported. The risk of bias was primarily “some concerns”, and the certainty of evidence ranged from moderate to low.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>VR appears effective in reducing pain and anxiety in adult patients in an in-hospital setting. It offers a relatively safe adjunct to standard care with minimal side effects. However, heterogeneity in outcomes and the risk of bias suggest a need for more standardised, high-quality trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>This systematic review with meta-analysis and trial sequential analysis provides updated evidence that virtual reality can significantly reduce anxiety and pain in patients undergoing surgical procedures. Through combining recent RCTs and cohort studies with robust methodological approaches, this review strengthens the evidence for VR as an effective non-pharmacological intervention. With minimal adverse events and significant improvements in recovery time, VR represents a scalable tool that can strengthen multimodal strategies and promote safer and more comfortable patient experiences.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"29 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ejp.70165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div> <section> <h3> Background</h3> <p>Chronic pain (CP) in older adults was associated with depression in numerous cross-sectional studies. However, the longitudinal link between CP characteristics and depressive symptoms in this population remains unsettled. We aimed to assess the prospective link between CP intensity and long-term depressive symptoms in a population-based cohort of older participants, considering numerous potential confounders.</p> </section> <section> <h3> Methods</h3> <p>The study sample was gathered from the PAQUID study, a prospective cohort study of community-dwellers above 65. Information regarding CP characteristics was collected at the 3-year follow-up visit. The sample included the 742 participants who fulfilled this CP questionnaire. Three CP groups were distinguished: no (<i>n</i> = 504), mild (<i>n</i> = 101), and intense (<i>n</i> = 137) CP. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression scale (CES-D) every 2–3 years during 12 years (6 waves). The association between CP and the 12-year CES-D course (12 years after the 3-year visit) was investigated using a multivariate latent process mixed model for curvilinear data.</p> </section> <section> <h3> Results</h3> <p>Compared with the participants without CP, those with moderate and intense CP had significantly higher CES-D levels at baseline with a dose–response relationship as a function of pain intensity (<i>β</i> = 0.366, <i>p</i> = 0.0308; 0.607, <i>p</i> < 0.0001, respectively). However, the time course was comparable in the three groups (<i>β</i> = −0.003, <i>p</i> = 0.8351; −0.003, <i>p</i> = 0.8516, for mild and intense CP, respectively).</p> </section> <section> <h3> Conclusion</h3> <p>CP intensity is associated with higher levels of depressive symptoms persisting throughout the long period of follow-up. This finding reinforces the importance of early treatment of CP in older adults to prevent its sustainable psychological consequences.</p> </section> <section> <h3> Significance Statement</h3> <p>Depression and chronic pain (CP) have been frequently associated in older adults. The longitudinal relationship between CP characteristics and the long-term course of depressive symptoms in this population has yet to be specified. The present results showed that CP intensity is associated with higher levels of depressive symptoms persisting throughout a 15-year follow-up period, with a dose–response relationship. This finding reinforces the importance of early treatment of CP in the older population, in order to prevent its last
{"title":"Baseline Chronic Pain Intensity and Long-Term Depressive Symptoms in French Older Community-Dwelling Adults: A 12-Year Prospective Cohort Study","authors":"Isabelle Rouch, Michèle Koleck, Arlette Edjolo, Karine Peres, Bernard Laurent, Jean-Michel Dorey, Jean-François Dartigues, Hélène Amieva","doi":"10.1002/ejp.70159","DOIUrl":"10.1002/ejp.70159","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic pain (CP) in older adults was associated with depression in numerous cross-sectional studies. However, the longitudinal link between CP characteristics and depressive symptoms in this population remains unsettled. We aimed to assess the prospective link between CP intensity and long-term depressive symptoms in a population-based cohort of older participants, considering numerous potential confounders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study sample was gathered from the PAQUID study, a prospective cohort study of community-dwellers above 65. Information regarding CP characteristics was collected at the 3-year follow-up visit. The sample included the 742 participants who fulfilled this CP questionnaire. Three CP groups were distinguished: no (<i>n</i> = 504), mild (<i>n</i> = 101), and intense (<i>n</i> = 137) CP. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression scale (CES-D) every 2–3 years during 12 years (6 waves). The association between CP and the 12-year CES-D course (12 years after the 3-year visit) was investigated using a multivariate latent process mixed model for curvilinear data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with the participants without CP, those with moderate and intense CP had significantly higher CES-D levels at baseline with a dose–response relationship as a function of pain intensity (<i>β</i> = 0.366, <i>p</i> = 0.0308; 0.607, <i>p</i> < 0.0001, respectively). However, the time course was comparable in the three groups (<i>β</i> = −0.003, <i>p</i> = 0.8351; −0.003, <i>p</i> = 0.8516, for mild and intense CP, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CP intensity is associated with higher levels of depressive symptoms persisting throughout the long period of follow-up. This finding reinforces the importance of early treatment of CP in older adults to prevent its sustainable psychological consequences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>Depression and chronic pain (CP) have been frequently associated in older adults. The longitudinal relationship between CP characteristics and the long-term course of depressive symptoms in this population has yet to be specified. The present results showed that CP intensity is associated with higher levels of depressive symptoms persisting throughout a 15-year follow-up period, with a dose–response relationship. This finding reinforces the importance of early treatment of CP in the older population, in order to prevent its last","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"29 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kaare Meier, Bettina Wulff Risør, Dennis Møgeltoft Poulsen, Jens Christian Hedemann Sørensen, Nasrin Tayyari
Background
Spinal cord stimulation (SCS) constitutes a treatment option for patients with severe chronic pain responding insufficiently to pharmacological treatment. High device costs and expenses associated with surgical procedures and follow-up constitute a barrier to adoption. However, CNP patients also constitute a significant burden on public finances, with high public costs relating to health care utilisation, medicine, and lost work capacity.
Methods
We investigated the costs of SCS therapy from a healthcare perspective (primary and secondary healthcare and medicine costs) 3 years before and 3 years after initiation of the SCS therapy in a large, mixed, well-characterised patient cohort derived from a dedicated neuromodulation registry, including patients with different diagnoses and characteristics from three of the four Danish SCS centers. We additionally compared costs of productivity loss for patients under the age of retirement. Data on societal costs were retrieved from public Danish registries.
Results
Three hundred and eight-four patients were included. Total healthcare costs 3 years after SCS were significantly higher than 3 years before SCS, with an increase of €29,835. The expenses associated with establishing SCS therapy are reflected in a sharp increase in in-patient secondary health care cost in year one after SCS. Primary health care, secondary out-patient health care and medicine costs all decrease after SCS but not enough to compensate for the cost of establishing treatment. Costs due to productivity loss remain stable throughout the period.
Conclusions
Our findings highlight evaluating high-cost interventions within a broader cost framework to inform more efficient resource allocation in chronic pain management.
Significance
This study analyzes the real-world socioeconomic impact of spinal cord stimulation (SCS) in Denmark. By using data from public Danish registries, we find a sharp increase in in-hospital expenses at the year of implantation, only partially offset by a subsequent reduction in other health care expenses and medicine costs. These findings give unique insights into the financial aspects of SCS, offering a perspective for healthcare providers, policymakers, and patients when evaluating the long-term budgetary implications of this treatment.
{"title":"Societal Cost Analysis of Spinal Cord Stimulation in Chronic Pain Patients: A Danish Register-Based Study With 3 Years Follow-Up","authors":"Kaare Meier, Bettina Wulff Risør, Dennis Møgeltoft Poulsen, Jens Christian Hedemann Sørensen, Nasrin Tayyari","doi":"10.1002/ejp.70160","DOIUrl":"10.1002/ejp.70160","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spinal cord stimulation (SCS) constitutes a treatment option for patients with severe chronic pain responding insufficiently to pharmacological treatment. High device costs and expenses associated with surgical procedures and follow-up constitute a barrier to adoption. However, CNP patients also constitute a significant burden on public finances, with high public costs relating to health care utilisation, medicine, and lost work capacity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We investigated the costs of SCS therapy from a healthcare perspective (primary and secondary healthcare and medicine costs) 3 years before and 3 years after initiation of the SCS therapy in a large, mixed, well-characterised patient cohort derived from a dedicated neuromodulation registry, including patients with different diagnoses and characteristics from three of the four Danish SCS centers. We additionally compared costs of productivity loss for patients under the age of retirement. Data on societal costs were retrieved from public Danish registries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Three hundred and eight-four patients were included. Total healthcare costs 3 years after SCS were significantly higher than 3 years before SCS, with an increase of €29,835. The expenses associated with establishing SCS therapy are reflected in a sharp increase in in-patient secondary health care cost in year one after SCS. Primary health care, secondary out-patient health care and medicine costs all decrease after SCS but not enough to compensate for the cost of establishing treatment. Costs due to productivity loss remain stable throughout the period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings highlight evaluating high-cost interventions within a broader cost framework to inform more efficient resource allocation in chronic pain management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This study analyzes the real-world socioeconomic impact of spinal cord stimulation (SCS) in Denmark. By using data from public Danish registries, we find a sharp increase in in-hospital expenses at the year of implantation, only partially offset by a subsequent reduction in other health care expenses and medicine costs. These findings give unique insights into the financial aspects of SCS, offering a perspective for healthcare providers, policymakers, and patients when evaluating the long-term budgetary implications of this treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"29 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Posters in Viewing Sessions","authors":"","doi":"10.1002/ejp.70133","DOIUrl":"https://doi.org/10.1002/ejp.70133","url":null,"abstract":"","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"29 S1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tessa Schillemans, Ann-Sofie Rönnegård, Themistocles L. Assimes, Magnus Peterson, Per Wändell, Lars Lind, Johan Ärnlöv
Background
Joint pain and chronic back pain are highly prevalent in the aging population and have a large impact on life quality. As the underlying mechanisms are not fully understood, this exploratory cross-sectional study aimed to discover proteins and pathways associated with these two pain conditions in Swedish 70-year-old men.
Methods
Plasma proteins (n = 720) were measured in participants from the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 931) using Olink target panels. Participants self-reported current joint pain or continuous back pain during the past year. We used logistic regression with multiple testing adjustments and RIDGE regression (selecting ~10% highest-ranking proteins) to identify proteins associated with either joint or chronic back pain, which were then investigated for clusters and pathway enrichments.
Results
Out of 931 subjects with protein data, 131 reported joint pain and 31 reported chronic back pain. We identified 19 (significant after multiple testing adjustment) and 25 (nominally significant) highest-ranking proteins associated with joint and chronic back pain, respectively. Enriched pathways included immune responses, inflammation, lipid, coagulation and rheumatoid arthritis pathways. Similar pathways were found for both joint and chronic back pain, even though only two proteins were associated with both these pain conditions.
Conclusions
This exploratory proteomics study provides support for systemic inflammation as a common underlying mechanism for joint and chronic back pain. Although similar pathways were found for both pain conditions, the selected proteins differed. Nevertheless, caution is advised due to low sample size and validation in larger studies including both women and men is needed.
Significance Statement
Logistic and RIDGE regression analyses indicated that joint pain and chronic back pain were associated with different proteins, which were enriched for similar inflammatory pathways.
背景关节痛和慢性背痛在老年人群中非常普遍，对生活质量有很大影响。由于潜在的机制尚不完全清楚，这项探索性横断面研究旨在发现与瑞典70岁男性这两种疼痛状况相关的蛋白质和途径。方法使用Olink靶板对乌普萨拉成年男性纵向研究（ULSAM; n = 931）参与者的血浆蛋白（n = 720）进行测量。参与者在过去一年中自我报告当前的关节疼痛或持续的背部疼痛。我们使用多重测试调整的逻辑回归和RIDGE回归（选择~10%的最高排名的蛋白质）来确定与关节或慢性背痛相关的蛋白质，然后研究这些蛋白质的簇和通路富集。结果在931名有蛋白质数据的受试者中，131名报告关节疼痛，31名报告慢性背痛。我们分别确定了19个（在多次测试调整后显著）和25个（名义上显著）与关节和慢性背痛相关的最高级蛋白。富集的途径包括免疫反应、炎症、脂质、凝血和类风湿性关节炎途径。在关节痛和慢性背痛中发现了类似的途径，尽管只有两种蛋白质与这两种疼痛有关。这项探索性蛋白质组学研究为全身性炎症作为关节和慢性背痛的共同潜在机制提供了支持。虽然在两种疼痛条件下发现了相似的途径，但选择的蛋白质不同。然而，由于样本量小，需要在包括女性和男性的大型研究中进行验证，因此建议谨慎。Logistic和RIDGE回归分析表明，关节痛和慢性背痛与不同的蛋白质相关，这些蛋白质富集于相似的炎症途径。
{"title":"An Exploratory Study for Proteomic-Based Markers of Joint Pain and Chronic Back Pain","authors":"Tessa Schillemans, Ann-Sofie Rönnegård, Themistocles L. Assimes, Magnus Peterson, Per Wändell, Lars Lind, Johan Ärnlöv","doi":"10.1002/ejp.70158","DOIUrl":"https://doi.org/10.1002/ejp.70158","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Joint pain and chronic back pain are highly prevalent in the aging population and have a large impact on life quality. As the underlying mechanisms are not fully understood, this exploratory cross-sectional study aimed to discover proteins and pathways associated with these two pain conditions in Swedish 70-year-old men.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Plasma proteins (<i>n</i> = 720) were measured in participants from the Uppsala Longitudinal Study of Adult Men (ULSAM; <i>n</i> = 931) using Olink target panels. Participants self-reported current joint pain or continuous back pain during the past year. We used logistic regression with multiple testing adjustments and RIDGE regression (selecting ~10% highest-ranking proteins) to identify proteins associated with either joint or chronic back pain, which were then investigated for clusters and pathway enrichments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Out of 931 subjects with protein data, 131 reported joint pain and 31 reported chronic back pain. We identified 19 (significant after multiple testing adjustment) and 25 (nominally significant) highest-ranking proteins associated with joint and chronic back pain, respectively. Enriched pathways included immune responses, inflammation, lipid, coagulation and rheumatoid arthritis pathways. Similar pathways were found for both joint and chronic back pain, even though only two proteins were associated with both these pain conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This exploratory proteomics study provides support for systemic inflammation as a common underlying mechanism for joint and chronic back pain. Although similar pathways were found for both pain conditions, the selected proteins differed. Nevertheless, caution is advised due to low sample size and validation in larger studies including both women and men is needed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>Logistic and RIDGE regression analyses indicated that joint pain and chronic back pain were associated with different proteins, which were enriched for similar inflammatory pathways.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"29 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ejp.70158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145407343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemotherapy-induced peripheral neuropathy (CIPN), characterised by a stocking-glove distribution of numbness and pain, is a severe clinical challenge. Our previous study showed that overexpression of neuronal G protein-coupled receptor kinase (GRK2) in the spinal dorsal horn (SDH) prevented cisplatin-induced CIPN in mice. The underlying mechanism, however, remains unclear. This study aimed to explore the role of insulin-like growth factor 1 (IGF1) in preventing CIPN through neuronal GRK2 in the SDH of mice.
Methods
CIPN model was established by intraperitoneally injecting cisplatin (23 mg/kg) in mice. Neuronal IGF1R or GRK2 in SDH was downregulated by intraspinally injecting an AAV vector delivering IGF1R or GRK2 shRNA with hSyn promoter. Mechanical allodynia and sensory deficits were assessed by von Frey test and adhesive removal test. The expression of IGF1, IGF1R and Iba1 was assessed by immunostaining. Neuroinflammation was assessed by real-time PCR. The IGF1R and GRK2 levels were assessed by Western blot.
Results
Cisplatin chemotherapy induced a decrease of IGF1 and p-IGF1R in SDH; intrathecal (i.t) injection of recombinant IGF1 (rIGF1) significantly prevented cisplatin-induced mechanical allodynia, sensory deficit, and microglia activation and neuroinflammation in SDH. IGF1R was primarily localised within neurons (~81%). Downregulation of neuronal IGF1R (AAV-shIGF1R) inhibited the preventive effect of i.t. rIGF1 on CIPN, and on the upregulation of GRK2 in SDH. Furthermore, downregulation of neuronal GRK2 in SDH inhibited the preventive effect of i.t. rIGF1 on CIPN.
Conclusions
I.t. injection of rIGF1 regulates neuronal GRK2 through neuronal IGF1R in SDH, alleviates microglial activation and neuroinflammation, thereby preventing cisplatin-induced CIPN.
Significance Statement
This work elucidates the role of neuronal IGF1/IGF1R in the process of CIPN prevention and provides new animal-based evidence for CIPN prevention by targeting neuronal IGF1/IGF1R in SDH.
{"title":"Targeting Upregulation of Neuronal IGF1/IGF1R Signalling in the Spinal Cord Prevents Cisplatin-Induced Peripheral Neuropathy in Mice","authors":"Chieh-Ru Fu, Jia-Hao Chen, Ya-Chen Yang, Hui Chen, Ruo-Fan Zhang, Yu-Xia Chu, Yan-Qing Wang, Qi-Liang Mao-Ying","doi":"10.1002/ejp.70161","DOIUrl":"https://doi.org/10.1002/ejp.70161","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chemotherapy-induced peripheral neuropathy (CIPN), characterised by a stocking-glove distribution of numbness and pain, is a severe clinical challenge. Our previous study showed that overexpression of neuronal G protein-coupled receptor kinase (GRK2) in the spinal dorsal horn (SDH) prevented cisplatin-induced CIPN in mice. The underlying mechanism, however, remains unclear. This study aimed to explore the role of insulin-like growth factor 1 (IGF1) in preventing CIPN through neuronal GRK2 in the SDH of mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CIPN model was established by intraperitoneally injecting cisplatin (23 mg/kg) in mice. Neuronal IGF1R or GRK2 in SDH was downregulated by intraspinally injecting an AAV vector delivering IGF1R or GRK2 shRNA with hSyn promoter. Mechanical allodynia and sensory deficits were assessed by von Frey test and adhesive removal test. The expression of IGF1, IGF1R and Iba1 was assessed by immunostaining. Neuroinflammation was assessed by real-time PCR. The IGF1R and GRK2 levels were assessed by Western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Cisplatin chemotherapy induced a decrease of IGF1 and p-IGF1R in SDH; intrathecal (i.t) injection of recombinant IGF1 (rIGF1) significantly prevented cisplatin-induced mechanical allodynia, sensory deficit, and microglia activation and neuroinflammation in SDH. IGF1R was primarily localised within neurons (~81%). Downregulation of neuronal IGF1R (AAV-shIGF1R) inhibited the preventive effect of i.t. rIGF1 on CIPN, and on the upregulation of GRK2 in SDH. Furthermore, downregulation of neuronal GRK2 in SDH inhibited the preventive effect of i.t. rIGF1 on CIPN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>I.t. injection of rIGF1 regulates neuronal GRK2 through neuronal IGF1R in SDH, alleviates microglial activation and neuroinflammation, thereby preventing cisplatin-induced CIPN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>This work elucidates the role of neuronal IGF1/IGF1R in the process of CIPN prevention and provides new animal-based evidence for CIPN prevention by targeting neuronal IGF1/IGF1R in SDH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"29 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145407425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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