BACKGROUND:The efficacy of caudal injections for patients with acute sciatica remains controversial. The DEXHIA study was designed to evaluate whether ultrasound-guided caudal injection of dexamethasone provides superior clinical outcomes compared with saline placebo. METHODS:This prospective, randomized, placebo-controlled, double-blind trial included adult patients with sciatica secondary to lumbar disc herniation of less than 3 months' duration. Participants were randomly assigned in a 1:1 ratio to receive either 16 mg of dexamethasone (4 mL) diluted with 16 mL of saline (DEXA group) or 20 mL of saline alone (PLACEBO group), administered by ultrasound-guided caudal epidural injection. The primary outcome was the change in the Oswestry Disability Index (ODI) at 3 weeks. Secondary outcomes included leg pain and low back pain assessed by visual analogue scale (VAS), health-related quality of life (SF-36), need for repeat epidural injection, and need for lumbar surgery. Clinical assessments were performed at 3 weeks, 3 months, and 6 months. RESULTS:A total of 106 patients were randomized, with 53 participants assigned to each treatment group. The primary endpoint was not met, as the improvement in ODI at 3 weeks did not differ significantly between groups (mean change: -9.5 ± 4.4 in the DEXA group versus -13.8 ± 4.4 in the PLACEBO group; p = 0.18). No significant differences were observed for any relevant secondary outcome at any follow-up time point. During the 6-month follow-up, 34 patients in the DEXA group and 30 patients in the PLACEBO group underwent a second, non-blinded injection of dexamethasone (ns). Lumbar surgery was performed in 10 patients in the DEXA group and nine patients in the PLACEBO group (ns). Injection-related adverse events were mild and transient but occurred more frequently in the DEXA group. CONCLUSIONS:Caudal injection of soluble dexamethasone conferred no clinical benefit over saline placebo in patients with acute sciatica. SIGNIFICANCE STATEMENT:Epidural injections are widely used worldwide for the treatment of resistant sciatica and have been extensively studied in multiple meta-analyses. However, their clinical value remains debated due to the limited methodological quality of most available studies. We conducted a methodologically rigorous randomized, placebo-controlled trial, which yielded negative results. These findings question the efficacy of caudal epidural injection of a non-particulate corticosteroid administered via a remote (sacrococcygeal) approach for disc-related sciatica. TRIAL REGISTRATION:The trial was registered under European Clinical Trials No. 2021-001571-17 and ClinicalTrials.gov identifier NCT05000658.
BACKGROUND:A substantial proportion of people with fibromyalgia also experience comorbid disorders of gut-brain interaction (DGBIs), which can lead to considerable personal and societal burdens. However, evidence regarding the implications of this comorbidity remains limited. The aim of this study was to investigate the occurrence of DGBIs in fibromyalgia, potential consequences for people when this happens, and a process called psychological flexibility (PF) that might help. METHODS:395 adults with fibromyalgia completed an online survey and were included in the analyses. Analyses included group comparisons, correlations, and mediation models. RESULTS:79.2% of the participants reported having at least one DGBI. Participants with multiple DGBIs reported significantly worse daily functioning compared with those without any DGBI. More severe gastrointestinal (GI) symptoms were correlated with more severe depression and worse daily functioning (r = 0.41 to 0.56, p < 0.001). PF statistically mitigated the relationship between GI symptom severity and depression and daily functioning (b = 0.05-0.13). CONCLUSIONS:While people with comorbid fibromyalgia and DGBIs report worse functioning, PF appears to modestly buffer the relationship between DGBI symptom severity and mood and daily functioning. Therefore, treatments that target PF, such as Acceptance and Commitment Therapy (ACT), may help address the challenges faced by this population. Longitudinal studies with experimental designs are needed to further explore the mediating role of PF and the utility of related treatments for this population. SIGNIFICANCE STATEMENT:This study investigates disorders of gut-brain interaction (DGBIs) in relation to psychological flexibility and functioning in people with fibromyalgia, and the prevalence of DGBIs in fibromyalgia in a large community sample. The findings show a high rate of co-occurring DGBIs and fibromyalgia. While the size of the effect was limited, psychological flexibility appears to act as a buffer in the relationship between symptom severity and functioning, suggesting that interventions targeting psychological flexibility may provide benefits for co-occurring conditions.
BACKGROUND:Complex regional pain syndrome (CRPS) is a chronic pain disorder that usually affects the limbs after injury, surgery or wearing a cast. However, currently, there are no effective treatments or drugs. No animal model mimics these symptoms and shows stable pain-like symptoms for the evaluation of therapeutic drugs. In this study, we developed a new mouse model that showed stable CRPS-like symptoms. METHODS:Male C57BL/6 mice were used for this study. The thigh was tied with a cable tie and 4 days later, the tie was removed. Pain was assessed by measuring licking duration and using von Frey filaments. The skin surface temperatures were measured using a thermography camera. RESULTS:Binding with a cable tie in the thigh induced swelling and inflammation. Three days after the removal of the tie, swelling and inflammation subsided. The duration of licking also increased significantly. Even after the tie was removed, the licking time continued to increase significantly for at least 24 days after its removal. In addition, after removing the tie, mechanical hypersensitivity was induced. Although the skin surface temperature in the leg decreased after cable tie binding, the temperature immediately increased to the level of that of non-treated mice after removing the tie. CONCLUSIONS:Cable tie binding for 4 days induced pain-related behaviours (mechanical hypersensitivity and prolonged licking) without swelling and inflammation of the calves after removal of the tie. Therefore, it is suggested that this mouse model is useful as an animal model that exhibits CRPS-like symptoms. SIGNIFICANCE STATEMENT:Previous animal models of complex regional pain syndrome (CRPS) did not show long-term pain-like symptoms. In this study, we developed an animal model that exhibited long-term pain-like symptoms without skin symptoms by tying a cable tie to the hind thigh with a constant force. This animal model is expected to be useful not only for elucidating the mechanism of CRPS development but also for drug development.
BACKGROUND:One explanation for the hypoalgesic effects of pleasant music is that these stimuli impact pain by eliciting positive emotion. However, it is not clear how much of this effect is due to attentional bias, as pleasant music may more effectively capture attention than neutral or aversive control conditions. As pain reduction by distraction and emotion represent distinct mechanistic pathways, differentiating the role of attention from that of emotion and mood is necessary to understand how pleasant music impacts pain. METHODS:If effects are due to attention, performing a challenging cognitive task during music listening should attenuate analgesia through competition for limited cognitive resources. We investigated this possible sub-additive interaction using a within-subject factorial design. Pain-free, healthy participants received thermal stimulations as they completed easy and difficult tasks while listening to music, scrambled music, or silence. We then assessed an interaction effect between the effects of task and music condition to test whether the auditory manipulation's effect on pain varied with task difficulty. RESULTS:The type of auditory stimulation and type of task had independent effects on pain intensity and unpleasantness, where music reduced pain in comparison to scrambled music and the 2-back reduced pain compared to an easier task. Tests for a possible interaction between the two factors did not support the hypothesis that music and cognitive tasks both reduce pain by demanding attention. CONCLUSIONS:While listening to music involves attentional processes that facilitate distraction, our results suggest that the emotional impacts of music can operate independently of these processes. SIGNIFICANCE STATEMENT:What makes music hypoalgesic, is it simply the distraction it provides? This study is the first to disentangle the role of attention from other mechanisms, finding that music can reduce pain independently of where attention is directed. These results have direct implications for music therapy, supporting the centrality of other mechanisms such as emotion in therapeutic frameworks and highlight the importance of examining both attentional and emotional pathways to pain relief in future mechanistic research.
INTRODUCTION:Erythromelalgia is a rare disorder characterised by burning pain, erythema and increased skin temperature in the extremities. Its pathophysiological heterogeneity, together with variable treatment responses, complicates management in the absence of evidence-based guidelines. This systematic review appraised pain-management strategies across reported aetiological subtypes. DATABASES AND DATA TREATMENT:Following PRISMA 2020 guidelines, the review was registered in PROSPERO (CRD420251232074). PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were searched for studies published or registered between 1 January 2000 and 30 April 2026. Randomised controlled trials, non-randomised interventional studies, cohort studies and case series were eligible; non-randomised studies required at least five individuals. Risk of bias was assessed using Joanna Briggs Institute tools and certainty of evidence using GRADE. RESULTS:Of 3372 records, 25 studies reporting 591 individuals were included. Aetiological subtype was reported for 277 individuals (46.9%). Mechanistic and aetiological characterisation varied substantially across domains, with haematological data available for 72.6% and SCN9A status for 19.0% of the overall population. Moderate-certainty evidence supported aspirin in myeloproliferative neoplasm-associated erythromelalgia. Low-certainty evidence suggested benefit from mexiletine and carbamazepine in primary erythromelalgia, as well as from prostaglandin analogues, corticosteroids, selected topical therapies and sympathetic interventions in specific contexts. Evidence for selective Naᵥ1.7 inhibitors and most other interventions was of very low certainty. CONCLUSIONS:Treatment-response patterns in better-characterised populations suggest that aetiology and underlying mechanisms may be relevant to treatment selection. However, this mechanism-informed approach remains hypothesis-generating and requires prospective validation through systematic aetiological and mechanistic characterisation. SIGNIFICANCE STATEMENT:This systematic review provides a comprehensive, graded evaluation of the full spectrum of pain-management strategies in erythromelalgia, including systemic, topical, interventional and non-pharmacological approaches, across reported aetiological subtypes. Integrating risk-of-bias appraisal and GRADE certainty ratings, it identifies moderate-certainty evidence for aspirin in myeloproliferative neoplasm-associated disease and low-certainty evidence for conventional sodium-channel blockers in selected primary forms, while evidence for other interventions remains low or very low. These patterns suggest that aetiology may inform treatment selection, but require prospective validation.
BACKGROUND AND OBJECTIVE:Non-specific low back pain (LBP) frequently becomes persistent or recurrent. This systematic review and meta-analysis determined whether physical, psychophysical or psychological variables can predict persistent or recurrent non-specific LBP. DATABASE AND DATA TREATMENT:Studies investigating physical, psychophysical or psychological predictors of persistent/recurrent LBP, pain intensity or disability were included. MEDLINE, EMBASE, APA PsycINFO, PubMed, CINAHL Plus, Web of Science, Scopus, ZETOC and OpenGrey were searched until January 2025. Risk of bias of individual studies was assessed using QUIPS and the certainty of evidence using GRADE. RESULTS:Fifteen studies were included, all addressing persistent LBP, examining one physical predictor domain (trunk kinematics), one psychophysical predictor domain (pain sensitivity) and seven psychological domains (depression-distress, anxiety, fear avoidance, catastrophising, somatisation, pain coping strategy, pain self-efficacy). Depression and distress significantly predicted persistent LBP and disability (n = 15,778; β = 0.28, 95% CI: 0.04 to 0.53, p = 0.024), and fear avoidance also significantly predicted persistent LBP and disability (n = 1105; β = 0.24, 95% CI: 0.00 to 0.49, p = 0.049), albeit both with low certainty of evidence. Enhanced temporal summation of pain was not a significant predictor of pain outcomes (n = 192; β = 0.10, 95% CI: -0.37 to 0.57), with very low certainty of evidence. Physical predictors showed limited and inconclusive evidence. Overall, the certainty of evidence ranged from very low to low across all predictor domains. CONCLUSION:Psychological factors, particularly depression-distress and fear avoidance, may predict LBP persistence, although higher quality studies are needed. SIGNIFICANCE STATEMENT:Depression-distress and fear avoidance are significant predictors of persistent non-specific low back pain, while evidence for physical predictors remains limited. These findings emphasize the need for early identification of modifiable psychological risk factors. TRIAL REGISTRATION:PROSPERO (Registration number CRD42024599514).
BACKGROUND:Previous reviews report moderate reductions in clinical pain with hypnotic suggestion but provide only partial views by comparing hypnosis with inactive controls alone or including few studies or mixed control groups. This review comprehensively evaluated the efficacy of hypnosis in reducing clinical pain intensity compared with non-active and active controls. METHODS:Systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) review guidelines with comprehensive literature search and meta-analysis. A total of 106 studies met inclusion criteria; 104 effect sizes from 84 studies were pooled using random-effects models, and 22 studies were narratively synthesised. Five databases were searched from inception to October 2025 for randomised controlled trials evaluating hypnosis versus non-active or active non-pharmacological controls for clinical pain intensity. Two independent reviewers screened articles and extracted data using standardised tools. RESULTS:Meta-analysis of 57 studies (4572 participants) showed reduced post-intervention pain following hypnosis versus non-active controls (SMD -0.33). Pre-post change scores yielded a comparable but non-significant effect (SMD -0.31). Subgroup analyses showed no differences by pain type, control type or delivery mode. Hypnosis did not outperform active controls, including relaxation (14 studies, SMD -0.13), pain education (7 studies, SMD -0.17 to -0.19) or cognitive-behavioural therapy (5 studies, SMD -0.32). CONCLUSIONS:Hypnosis yields modest reductions in clinical pain comparable to other psychological interventions. SIGNIFICANCE STATEMENT:This review provides a comprehensive synthesis of randomised trials evaluating hypnosis for clinical pain intensity, distinguishing non-active from active comparators and examining delivery mode, pain type and risk of bias. Hypnosis produced only small reductions in pain and did not clearly outperform relaxation, pain education or cognitive-behavioural therapy. These findings refine expectations for hypnoanalgesia, suggesting it may provide low-risk supportive care for selected patients, but should not be presented as a reliably superior pain-reduction treatment option. TRIAL REGISTRATION:Prospero (CRD42024608722).
BACKGROUND AND OBJECTIVES:Multiple sclerosis (MS) is a neurodegenerative disorder frequently leading to neuropathic pain. Due to the neurodegenerative nature, the diagnosis of neuropathic pain remains challenging. A grading system has been developed providing an overview of diagnostic certainty (i.e., possible, probable and definite). Since no previous review has accounted for this, differences in diagnostic certainty may have affected prevalence estimates. To elucidate this issue, the current meta-analysis aimed to estimate the prevalence of possible, probable and definite neuropathic pain separately, as well as the overall prevalence of neuropathic pain in MS. DATABASES AND DATA TREATMENT:A comprehensive systematic literature review was conducted (by 14-10-2025) using PubMed, Embase and Scopus databases, adhering to the PRISMA guidelines. For the meta-analysis, we applied the Generic Inverse Variance method, using a random-effects model for proportions to compute prevalence estimates for possible, probable and definite neuropathic pain, as well as for overall prevalence. RESULTS:The literature search yielded 1638 records, of which 32 papers were considered eligible for inclusion. Disregarding diagnostic certainty, the overall prevalence of neuropathic pain in people with MS was estimated at 22.3% (95% CI: 17.3; 27.3). Following stratification by diagnostic certainty, the prevalence of possible neuropathic pain was 22.0% (95% CI: 16.0; 28.0), probable neuropathic pain was 23.7% (95% CI: 19.4; 28.0), and definite neuropathic pain was 23.4% (95% CI: 1.11; 35.8). CONCLUSIONS:Neuropathic pain in MS was estimated at an overall prevalence of 22.3%. Moreover, estimates of neuropathic pain in MS across diagnostic certainty levels yielded numerically similar results. However, these findings may not provide evidence of comparability; rather, they reflect methodological heterogeneity among the included studies. As such, in line with international recommendations, a diagnosis of possible neuropathic pain appears appropriate for epidemiological purposes as well as for initial screening in pwMS. However, probable and/or definite diagnoses should be adopted in clinical practice and in future studies investigating pain-phenotype-based effects in pwMS. SIGNIFICANCE STATEMENT:This review estimates the prevalence of neuropathic pain in multiple sclerosis across NeuPSIG diagnostic certainty levels, providing novel and valuable methodological insights into the application of the grading framework. Findings support the use of possible neuropathic pain for epidemiological and screening purposes, while emphasizing the importance of probable or definite diagnoses for clinical practice and pain-phenotype-based research. The review also highlights limitations of the framework and operationalization thereof that can inform future applications and refinements, particularly for central neuropathic pain, where diagnostic classification remains inherently challenging.
BACKGROUND:There is limited evidence on the physical and psychological features present during remission from non-specific neck pain, yet this may be relevant for the high incidence of neck pain recurrence. METHODS:A cross-sectional study design was conducted with 60 participants (20 per group: healthy controls, people in remission from recurrent neck pain, current chronic neck pain) who were assessed for pressure pain thresholds, conditioned pain modulation, cervical kinematics, proprioception, neck muscle strength, neck muscle activity via electromyography, force steadiness, endurance, and psychological features. RESULTS:People in remission and those with current neck pain demonstrated reduced maximal velocity (p ≤ 0.05) and smoothness of movement (p ≤ 0.05) during neck extension, rotation, and side flexion compared to controls. Shoulder shrug strength (p ≤ 0.001) was also reduced in both pain groups. Maximal angular velocity and smoothness of neck flexion movement, as well as peak neck extension strength, were reduced only in those in remission compared to controls (p ≤ 0.01). Those with current neck pain distinctively showed reduced neck flexion strength, reduced force steadiness during submaximal neck flexion and extension contractions, heightened antagonist coactivity, and less endurance for the neck flexors and extensors (p ≤ 0.05). CONCLUSION:Individuals in remission from neck pain exhibit some alterations in cervical kinematics, motor output and neuromuscular control resembling similar impairments to those with current chronic neck pain despite being pain-free. Such features may be relevant for pain recurrence, and this should be explored in future longitudinal studies. SIGNIFICANCE STATEMENT:This study identifies changes in physical function of the neck which are present in people with active chronic non-specific neck pain that are also evident during remission from pain. Such findings provide an understanding of the previously underexplored clinical presentation during neck pain remission. If determined to be relevant, specific interventions to target these changes could be provided to optimise functional capacity with the aim of minimising or preventing the recurrence of pain.
BACKGROUND:Pharmacological combinations are commonly used for treating refractory neuropathic pain, although supporting evidence is lacking. Gabapentinoid-opioid combination is one of the most studied; however, their efficacy is inconsistent across clinical trials. This trial investigated the feasibility, effectiveness and safety of adding pregabalin to buprenorphine for managing this condition. METHODS:This single-center, phase IV, double-blind, placebo-controlled trial enrolled adults with peripheral chronic neuropathic pain, refractory to tricyclic antidepressants and/or serotonin-norepinephrine reuptake inhibitors. Participants were randomized to receive transdermal buprenorphine up to 20 mcg/day, plus pregabalin up to 300 mg/day (group C) or placebo (group M). Participants underwent a 3-week tolerability-based dose titration and a 6-week maintenance phase. Primary outcome was ≥ 30% average pain reduction at week 9. RESULTS:Sixty individuals (66.7% female, 53 [45-58.5] years old) were enrolled. After titration, pregabalin dose was 100 mg/day for most group C participants (87%), and transdermal buprenorphine doses were similar between groups (p = 0.787). At week 9, ≥ 30% pain reduction was achieved by 38% in group C and 32% in group M (p = 0.942). Pain interference, mood, anxiety and quality-of-life scores did not significantly differ between groups. Baseline pain phenotype was not associated with primary outcome results. Side-effect frequencies were similar between groups, and no serious adverse events occurred. CONCLUSIONS:Adding pregabalin to transdermal buprenorphine was not found to be effective for treating neuropathic pain. However, low-to-moderate analgesic effects cannot be excluded. Although no major side effects occurred, opioid use may have led to lower pregabalin tolerability, hindering the feasibility of this combination in clinical practice. SIGNIFICANCE STATEMENT:Although pharmacological combinations are widely prescribed for neuropathic pain (NP), consistent evidence of their benefit is lacking. This phase IV, pragmatic trial does not support the effectiveness of pregabalin-buprenorphine combination for refractory NP, even across distinct pain phenotypes. Besides suggesting the poor feasibility of this combination due to poor tolerability, it adds to the mounting evidence challenging earlier reports of an opioid-sparing effect for gabapentinoids. Clinical Study Registration Number: 52145215.0.0000.0068.
BACKGROUND:Musculoskeletal pain presentations are heterogeneous, but routine intake assessment often relies on individual symptom scores rather than multidimensional psychosocial patterns. In this study, we aimed to identify self-reported psychosocial profiles among adults with chronic musculoskeletal pain attending a self-funded manual bodywork therapy service in Japan. METHODS:We analysed baseline data from consecutive adult attendees. Of 21,498 eligible participants, 20,341 had complete profiling data, and 12,235 with pain duration ≥ 3 months formed the primary analytic sample. Latent profile analysis used four standardized total-score indicators: pain intensity, Central Sensitization Inventory-9 (CSI-9), Pain Catastrophizing Scale (PCS) and Tampa Scale for Kinesiophobia-11 (TSK-11). Solutions with two to 10 profiles were evaluated using fit, classification precision, profile size, stability, parsimony and interpretability. RESULTS:A six-profile solution was retained: high pain/lower fear (1028; 8.4%), globally low burden (645; 5.3%), low-to-moderate burden (2686; 22.0%), intermediate burden (4113; 33.6%), globally elevated burden (575; 4.7%) and psychosocially elevated burden (3188; 26.1%). Catastrophizing and kinesiophobia more strongly differentiated profiles than pain intensity alone. High pain/lower fear showed high pain intensity with comparatively lower kinesiophobia, whereas psychosocially elevated burden showed prominent catastrophizing and kinesiophobia despite less extreme pain intensity and CSI-9 scores than globally elevated burden. CONCLUSIONS:Six self-reported psychosocial profiles were identified in this self-funded chronic musculoskeletal pain cohort. The findings are descriptive and hypothesis-generating and require longitudinal and external validation before prognostic or treatment-stratification use. SIGNIFICANCE STATEMENT:Using routine intake data from 12,235 adults with chronic musculoskeletal pain, this study identified six self-reported psychosocial profiles that were not reducible to pain intensity alone. The findings support future validation of brief multidimensional intake assessment for profile-informed stratified care.
BACKGROUND:Chronic postsurgical pain (CPSP) after video-assisted thoracoscopic surgery (VATS) is common, yet clinicians lack tools to identify high-risk patients at routine follow-up. We hypothesized that pain with neuropathic characteristics at 2 weeks, signifying central sensitization, could stratify risk and guide precision analgesia. METHODS:This prospective cohort study enrolled 500 adults undergoing VATS lung resection. Two logistic models were developed: one using variables on postoperative day 1 (POD1), and another adding neuropathic pain features on POD14. The primary outcome was CPSP at 3 months, defined as a Numerical Rating Scale [NRS] score ≥ 1 for pain in the surgical region that was not present preoperatively and was not attributable to malignancy or infection; sensitivity analysis was conducted using NRS ≥ 3. Discrimination (area under the curve [AUC]), calibration and decision curve analysis quantified predictive performance and potential clinical applicability. RESULTS:Of 483 patients analysed, 247 (51.1%) developed CPSP and 184 (38.1%) had 3-mon NRS ≥ 3. The POD14 model (sex, surgery type, chest tube duration, pain intensity, pain with neuropathic characteristics) was superior (AUC 0.904, 95% CI: 0.872-0.936) to the POD1 model (AUC 0.865, 95% CI: 0.827-0.903). Neuropathic pain at 2 weeks was the strongest predictor (odds ratio 13.98, 95% CI: 2.90-67.38). Temporal validation confirmed discrimination with good calibration. Sensitivity analysis showed an AUC of 0.786 (95% CI: 0.737-0.835) for the POD14 model; pain with neuropathic characteristics retained strong predictive value. CONCLUSIONS:This 5-item tool with neuropathic pain features at 2-week visit identifies patients at high risk for CPSP after VATS. SIGNIFICANCE STATEMENT:Translating central sensitization from a theoretical mechanism to an actionable bedside tool, this study demonstrates that neuropathic pain features captured at routine two-week follow-up stratify risk for CPSP after VATS. This 5-item model is a first step toward individualized CPSP risk stratification after VATS and requires external validation before clinical implementation.
BACKGROUND:Chronic spinal pain is a major public health challenge, but its management seldom considers the environmental impact of healthcare practices. This study aimed to identify consensus-based recommendations for integrating environmental sustainability into chronic spinal pain care. METHODS:Clinical practice guidelines on chronic spinal pain and literature on sustainable practices were reviewed to develop an initial set of statements. Following the ACCORD reporting guideline, a modified three-round Delphi study was conducted to obtain international consensus on the statements' agreement and importance. Physiotherapists from clinical, educational, and research backgrounds participated. The initial domains included environmental advocacy and policies, education, research and innovation, community engagement, sustainable clinical practices. Consensus was defined as an interquartile range (IQR) ≤ 1 for both dimensions. RESULTS:The preparatory review of clinical guidelines and sustainability literature identified five domains and informed the development of 47 statements and seven questions. Of the 150 experts invited, 49 participated (44 in Round 1, 35 in Round 2, 30 in Round 3), representing diverse clinical, educational, and research backgrounds from multiple world regions. By the end of the three rounds, 49 statements were classified as consensus recommendations; items with a median of 3 were reported separately as uncertain statements. CONCLUSIONS:This international Delphi study achieved broad consensus on integrating sustainable physiotherapy practices for chronic spinal pain management. The findings contribute to a framework that can inform future guidelines and orient research, education, and policy toward more sustainable care. SIGNIFICANCE STATEMENT:Chronic spinal pain management is increasingly promoted within conservative care models, yet its environmental sustainability remains largely unexplored in pain research. This international modified Delphi study establishes expert consensus on integrating sustainability considerations into physiotherapy for chronic spinal pain. By providing a structured framework, the findings inform future research agendas, guideline development, and professional education, contributing to more sustainable and responsible pain management aligned with planetary health challenges.
BACKGROUND:Although a key factor in understanding intergenerational transmission, family history of chronic pain deserves greater attention, particularly about its role as a potential mediating factor on current psychophysical status, together with other underestimated parameters (e.g., psychiatric comorbidity). The aims of this cross-sectional study were to explore the role of family history of chronic pain in the severity of current clinical status and to examine its association with current psychiatric comorbidity in a sample of adults with chronic pain during their first consultation at a specialist pain service in Italy. METHODS:174 patients were consecutively recruited within the 'Pain Therapy Service' at the Parma University Hospital. They completed the Brief Pain Inventory (BPI) and the Structured Clinical Interview for DSM-5 mental disorders (SCID-5). Inter-group comparisons were explored using the Chi-Square or the Mann-Whitney U test. Associations between family history of chronic pain and a wide range of other relevant clinical/sociodemographic parameters were analysed with binary logistic or multiple linear regression analyses. RESULTS:72 (41.4%) participants had a family history of chronic pain, with high concordance (68.1%) in the prevalence of the location of pain. Family history of chronic pain was found to predict higher levels of current unemployment and was significantly associated with greater current pain intensity and more frequent non-analgesic use of psychotropic drugs. CONCLUSIONS:A significant proportion of patients with chronic pain have a family history of chronic pain. Although a distal predisposing factor, family history of chronic pain negatively impacts current employment opportunities and contributes to increased individual pain-related suffering. SIGNIFICANCE STATEMENT:Regarding existing knowledge, the results of this research highlighted that participants with a family history of chronic pain represent a non-negligible proportion (40%) of chronic pain patients, who also show a high concordance (65%) in pain location with their family members. Further studies on the importance of individual (e.g., genetic vulnerability) and psychosocial (e.g., parental communication style and dysfunctional attachment) variables within the biopsychosocial paradigm are needed to better understand the causal interplay between contextual and internal factors. Anyway, psychosocial intervention can be very helpful in clinical practice to reduce the current impact of distal dysfunctional psychological elements. Furthermore, another interesting finding that emerged from this research is that although distal, this intergenerational relationship was found to predict higher levels of current unemployment and was associated with greater current pain intensity, contributing to negative clinical and functional outcomes in adulthood. Therefore, clinical monitoring of offspring is necessary to promote prevention/early intervention for chronic pain.
BACKGROUND:For decades, clinicians and researchers have struggled to classify pain conditions that do not fit neatly into the nociceptive, neuropathic or nociplastic frameworks. Many common disorders-from chronic low back pain to cancer pain and osteoarthritis-exhibit overlapping mechanisms and have long fallen into the 'grey zone' of mixed pain. This area has intrigued researchers yet frustrated clinicians due to the absence of a clear, unified definition. METHODS:Through an international consensus process led by global leading experts, mixed pain has now been defined as pain that is associated with a lesion, disease or disorder resulting in an overlap of at least two mechanistic pain descriptors (nociceptive, neuropathic or nociplastic). CONCLUSIONS:This new definition may help provide the context needed to align research, refine diagnosis and design mechanism-based therapies for patients with mixed pain. It marks an important step towards conceptual clarification-from confusion to consensus, from overlap to action-transforming mixed pain from an ambiguous concept into a potential framework of modern pain taxonomy. SIGNIFICANCE STATEMENT:This work provides an internationally unified consensus definition of mixed pain, addressing inconsistency in pain terminology and mechanistic classification. By defining mixed pain as the overlap of at least two mechanistic pain descriptors (nociceptive, neuropathic or nociplastic), the framework clarifies conceptual ambiguity while stressing the importance of identifying the underlying pain descriptors, supports a mechanism-based assessment and may facilitate more individualized treatment approaches in complex pain conditions while providing a practical foundation for future research, validation and clinical application.
