Pain and Therapy最新文献

Introduction: Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) or its receptor represent a major advance in migraine prevention. However, standardized criteria for assessing treatment response are lacking. This study aimed to compare responder rates based on monthly migraine days (MMDs), the Migraine Disability Assessment (MIDAS), and the Headache Impact Test (HIT-6), and to evaluate whether a single outcome measure may be sufficient for therapeutic decision-making.

Methods: In this retrospective, single-center study, 417 patients with episodic or chronic migraine treated with a CGRP or CGRP receptor monoclonal antibody between January 2020 and June 2023 were analyzed. Inclusion required complete documentation of MMDs, MIDAS scores, and HIT-6 scores. Response was defined as a ≥ 50% (episodic) or ≥ 30% (chronic) MMDs reduction, a ≥ 30% MIDAS reduction (baseline > 20), and/or a ≥ 5-point HIT-6 improvement.

Results: In episodic migraine, 50.3% of patients met the MMDs response criterion, while 69.5% and 67.5% responded as per MIDAS and HIT-6, respectively. In chronic migraine, the response rates were 58.2% (MMDs), 48.2% (MIDAS), and 55.0% (HIT-6). Combining all three parameters identified treatment response in 84.8% of episodic and 77.7% of patients with chronic migraine. Only 1.5% of patients with episodic migraine would have been misclassified as non-responders if solely PROMs were used. Treatment discontinuation due to adverse events occurred in 3.3% of patients.

Conclusions: Outcome measures strongly influence responder classification. PROMs such as MIDAS and HIT-6 captured therapeutic benefits not reflected in MMDs reductions, especially in cases of preserved headache frequency but reduced burden. These tools may serve as valid surrogates for diary-based documentation, especially in episodic migraine. PROMs are a practical and patient-centered alternative or complement to headache diaries, particularly under routine care constraints. Regulatory frameworks and clinical guidelines should consider integrating these measures into standard practice.

Diabetic peripheral neuropathic pain (DPNP) is becoming increasingly prevalent as the global burden of diabetes continues to rise. DPNP manifests moderate-to-severe pain with burning, shooting, and tingling sensations, which increase clinical and economic burden and reduce the quality of life (QoL). α₂δ ligands were developed on the basis of their mechanism of action involving the modulation of voltage-gated calcium channels (VGCCs). These ligands bind to the α₂δ subunit of VGCCs, which reduces calcium influx and subsequently decreases the release of excitatory neurotransmitters. A majority of the clinical trials have demonstrated the efficacy of α₂δ ligands in providing pain relief and improvement in the QoL for patients with DPNP. Furthermore, α₂δ ligands have a tolerable safety profile, with somnolence and dizziness being the most frequently reported adverse events. Currently, most guidelines recommend calcium channel α₂δ ligands as first-line treatment for DPNP. With the development of drug research, mirogabalin, an emerging novel α₂δ ligand, was developed and validated. This review aims to summarize the latest status of α₂δ ligand development and provide a comprehensive evaluation of α₂δ ligands for the management of DPNP, emphasizing the potential mechanism of action, clinical efficacy, safety profile, and pharmacoeconomics. Further perspectives are warranted for treatment strategies to address individual patient care.A Graphical Abstract is availible for this article.

Introduction: Hip/inguinal pain is a common symptom in athletes. Ultrasound (US) examination may discriminate causes, among which the iliopsoas muscle is often neglected. In the present case series study, we describe five patients with hip/inguinal pain where an accurate US evaluation of the iliopsoas muscle showed that the origin of the pain was due to alterations of the iliopsoas muscle complex, particularly of the fascia surrounding the medial fibers of the iliacus muscle (MFIM). We describe a novel pathological entity characterized by myofascial rigidity and hip/inguinal pain with thickening of the intramuscular fascia of the iliacus muscle and its epimysium, with increased stiffness of the muscle.

Methods: We studied five athletes with hip/inguinal pain on hip flexion-extension in the absence of hip and visceral pathologies. US was performed with linear probes studying the affected hip at the inguinal level, using longitudinal and axial scans. The examination was completed with power Doppler (PD), strain elastosonography (ELS), and strain ratio (SR) evaluation of the lateral and medial belly of the iliacus muscle.

Results: In all patients, we observed a thickening of the intramuscular fascia that surrounds the medial belly of the iliacus muscle. The mean ± standard deviation thickness of the intramuscular fascia of the iliacus muscle varied significantly between the affected and non-affected sides (2.70 ± 0.41 mm vs. 1.02 ± 0.15 mm, p value 0.012). In two out of five cases, an increase in the intramuscular perifascial vascular signals at PD was detected. All cases showed stiffness of the MFIM on ELS and altered SR in MFIM compared with the lateral ones in three out of five patients.

Conclusions: We describe a novel cause of a pathological condition of the iliopsoas muscle due to the thickening of the medial belly of the iliacus muscle, easily verifiable with US. All subjects responded to physical therapy with high-energy laser and stretching of the muscle unit. Video available for this article.

Introduction: Spinal cord stimulation (SCS) is a widely accepted therapy in patients with chronic intractable neuropathic pain in the trunk and limbs. However, open-loop (OL) SCS systems, which rely on fixed stimulation parameters and subjective feedback, face limitations in delivering consistent neural activation and durable pain relief. Anatomical and physiological characteristics of the cervical spinal cord, such as decreased cerebrospinal fluid thickness and increased mobility, exacerbate these challenges. Limited evidence exists on differences in cervical and thoracic neurophysiology, and the corresponding impact on neural activation in SCS. This post hoc analysis characterizes neurophysiological differences between the cervical and thoracic regions using evoked compound action potential (ECAP)-controlled closed-loop (CL) technology to assess implications for SCS dosing and therapy optimization.

Methods: Global study and real-world chronic pain patients implanted with ECAP-controlled CL-SCS systems were included. To identify differences between cervical (n = 187) and thoracic (n = 1899) neurophysiology, the relationship between stimulation current and neural activation was analyzed. Additionally, neural activation stability was evaluated in both in-clinic and out-of-clinic settings.

Results: The cervical spinal cord demonstrated significantly lower ECAP thresholds (p < 0.001) and > 100% higher spinal cord sensitivity compared to the thoracic region (p < 0.001). Cervical therapeutic dosing range was ≥ 48% narrower (p < 0.001), increasing the risk of overstimulation with OL-SCS. CL-SCS significantly improved dose accuracy in both regions (p < 0.001) during postural changes simulating activities of daily living. These findings highlight the superior precision and consistency in neural dosing with ECAP-controlled CL systems.

Conclusions: This is the first study to objectively characterize differences in cervical and thoracic spinal neurophysiology using SCS. ECAP-controlled CL-SCS maintains consistent neural activation in both cervical and thoracic regions. Given the heightened sensitivity and narrow dosing range in the cervical region, ECAP-controlled CL-SCS may enhance therapeutic outcomes through more precise and consistent neural dosing compared to OL systems.

Introduction: Topical nonsteroidal anti-inflammatory drug (NSAID) formulations provide significant pain relief with excellent tolerability in the local treatment of soft tissue injuries. This study aimed to assess the efficacy and safety of a novel etofenamate 70 mg medicated plaster for treatment of pain in patients with acute sprains, strains and contusions (bruises).

Methods: In this randomized, placebo-controlled trial patients with acute injuries of recent onset received etofenamate or placebo plasters (2:1) applied once daily for 7 days. Regular clinical assessments were made with focus on pain on movement (POM) in millimetres on a 100-mm visual analogue scale (VAS).

Results: A total of 180 adult patients (mean age 34.5 ± 13.5 years; 49.4% female) were enrolled. Mean VAS values for POM were 70.0 ± 6.3 mm at baseline; at 72 h POM had reduced by 59.0 mm and 33.3 mm in the etofenamate and placebo groups, respectively. Least squares mean treatment difference was 25.0 mm (p value for analysis of covariance < 0.0001). Results were consistent across type of injury (sprain/strain or contusion). Clinically meaningful superiority of etofenamate versus placebo was also seen for POM at the 24-, 48-, 96- and 120-h visits (p < 0.0001). Time to reach meaningful (30%), optimal (50%) and complete (100%) reduction of POM was significantly shorter with etofenamate. A significantly greater proportion of patients using etofenamate rated their progress and/or treatment as 'good' or 'very good'. The responder rate (proportion of patients with at least 50% pain reduction at 72 h) was 98.3% for etofenamate and 38.3% for placebo, resulting in a number needed to treat of 1.7, a value consistent with high effectiveness. The plasters adhered well over the 24-h dosing period and were very well tolerated.

Conclusion: In the setting of acute sprains, strains and contusions (bruises) the etofenamate plaster has therapeutic efficacy that is comparable to that for the best available topical NSAID formulations.

Registration: 2021-003778-30 (EudraCT number).

Introduction: Chronic pain is a major public health issue affecting approximately one-fifth of children and adolescents worldwide, and it is also a common complaint among Chinese adolescents. Despite its impact on daily functioning in this population, culturally adapted tools for assessing pain-related disability are lacking. The Functional Disability Inventory (FDI) is a widely used measure for evaluating functional impairment, but its simplified Chinese version has yet to be validated. This study aimed to translate and culturally adapt the FDI into simplified Chinese to assess its reliability and validity in measuring pain-related functional disability among Chinese adolescents.

Methods: First, the FDI was translated into simplified Chinese according to international guidelines. Subsequently, 1569 adolescents (aged 10-18) completed six scales: FDI, the Pain Catastrophizing Scale (PCS), the Depression Anxiety Stress Scales (DASS-21), the Tampa Scale for Kinesiophobia (TSK), the Children's Somatization Inventory (CSI), and the Wong-Baker Faces Pain Scale (WBS). After that, psychometric properties were evaluated, including internal consistency reliability (Cronbach's α and McDonald's ω), test-retest reliability (intraclass correlation coefficient and Pearson correlation coefficient), convergent validity (correlations with the other scales). In addition, the sample of 224 pediatric patients with functional abdominal pain (aged 8-18) was drawn to analyze the clinical validity by performing receiver operating characteristic (ROC) analysis.

Results: The Chinese FDI demonstrated strong internal consistency (α = 0.86; ω = 0.86) and acceptable test-retest reliability (ICC = 0.63; Pearson correlation coefficient was 0.64). Convergent validity was supported by significantly moderate correlations with all the other scales, coefficients ranging from r = 0.30 to r = 0.50 (p < 0.01). ROC analysis revealed excellent clinical validity, with an optimal cutoff score of ≥ 15 [area under the curve (AUC) = 0.90, sensitivity = 0.78, specificity = 0.92] for distinguishing adolescents with chronic pain from healthy peers.

Conclusions: The simplified Chinese FDI is a reliable and valid tool for assessing pain-related functional disability in Chinese adolescents. Its psychometric properties align with global versions while accounting for cultural differences, making it suitable for clinical and research use.

Introduction: Opioids are commonly used for postoperative pain management but are associated with adverse effects and risk of dependence, potentially hindering recovery. This systematic review evaluates the impact of opioid-sparing analgesic strategies on postoperative pain and functional recovery to provide evidence-based guidance for clinical practice and future research.

Methods: A comprehensive systematic review and meta-analysis was conducted by searching PubMed, Embase, Web of Science, and the Cochrane Library for randomized controlled trials on adult surgical patients from the inception of each database to July 10, 2024. The primary outcome was the total morphine consumption within 24 h postoperatively. Secondary outcomes included postoperative pain scores at 24 h, patient satisfaction, length of stay, quality of recovery, and opioid-related adverse effects, such as postoperative nausea and vomiting (PONV), sedation, dizziness, drowsiness, pruritus, urinary retention, and hypotension.

Results: A total of 58 studies (5614 patients) were included. The total morphine consumption was reduced, with a mean difference (MD) of -9.47, 95% confidence interval (95% CI) [-13, -5.95]. The postoperative pain score at 24 h was lower than in the control group, with an MD of -0.72 (95% CI [-0.97, -0.47]). Patient satisfaction was higher than in the control group, with an MD of 0.88 (95% CI [0.36, 1.40]). There were no significant differences in length of stay or recovery quality compared to the control group (P = 0.7, P = 0.48). The incidence of PONV was lower than the control group, with an odds ratio (OR) of 0.73 (95% CI [0.59, 0.90]), and the incidence of pruritus was also lower than in the control group, with an OR of 0.64 (95% CI [0.41, 0.98]). There were no differences in other adverse reactions compared to the control group.

Conclusion: The results of this meta-analysis indicate that, compared to opioid-based analgesia, opioid-sparing analgesia is associated with reduced morphine consumption within 24 h postoperatively, lower pain scores, and a decreased incidence of PONV and pruritus. Patient satisfaction was also improved. The findings will help clinicians make evidence-based decisions for postoperative pain management.

Trial registration: The protocol for this meta-analysis: PROSPERO CRD42024579882.

Introduction: Patient-reported outcomes (PROs), such as peri- and postoperative pain scores, capture patient perspectives in regional anesthesia trials. However, whether these outcomes are reported according to established guidelines remains unclear. The CONSORT statement and its PRO extension (CONSORT-PRO) aim to enhance transparency in reporting PROs, yet no study has investigated adherence in peripheral nerve block (PNB) trials. Our meta-epidemiological investigation evaluated how well PNB randomized controlled trials (RCTs) adhere with CONSORT-PRO and explored whether trial characteristics affect reporting quality.

Methods: We performed a cross-sectional, meta-epidemiological study to determine adherence to CONSORT-PRO reporting guidelines in RCTs. We searched Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and MEDLINE for RCT publications investigating PNBs between 2006 and 2020. RCTs investigating PNBs that incorporated PROs as a primary or secondary outcome were included. All other studies, reviews, or publications without a PRO were excluded.

Results: In total, 65 RCTs met the inclusion criteria. Mean CONSORT-PRO adherence was 46.80 ± 17.36%, and trials that designated a PRO as the primary endpoint were more adherent than those in which the PRO was secondary (49.27 ± 16.58% versus 38.57 ± 17.92%; P = 0.035). Trials with ≥ 6-month follow-up were 16.24% more adherent than those with ≤ 3-month follow-up (P = 0.006). Studies that used a visual analog scale (VAS) or numeric rating scale (NRS) in combination with other PRO instruments were significantly more adherent than trials using VAS alone (P = 0.028).

Conclusions: Our meta-epidemiological review reveals substantial nonadherence to CONSORT-PRO guidelines in PNB trials. Although PROs are crucial for capturing patient-centered outcomes, they remain under-reported, especially when treated as secondary endpoints. Using diverse, validated measures beyond VAS/NRS and consistently applying CONSORT-PRO can enhance the quality, transparency, and clinical relevance of future trials. Targeted education for authors, editors, and clinicians-and expanded research on neuraxial techniques-will further strengthen reporting standards and the interpretability of anesthesia evidence.

Introduction: Chronic pelvic pain syndrome (CPPS) is a diagnosis of exclusion in the absence of pathological findings. We aimed to test the hypothesis that cervical motion tenderness (or parametropathy) may serve as a diagnostic tool for CPPS.

Methods: We examined the prevalence of parametropathy in patients with and without chronic pelvic pain by analyzing consecutive vaginal examinations in 155 women ≥ 18 years. Patients with malignant pelvic tumors, acute inflammatory disease, abnormal bleeding, genital atrophy, or pregnancy were excluded. Results from repeat examinations were also excluded. Parametropathy was defined as tenderness at three different points (left, middle, and right vaginal fornix) on bimanual examination, expressed by the patient on a three-digit scale: Pain index 0, absent; 1, slight tenderness; 2, remarkable tenderness. A pain index (PI) of 2 at one or more sites was considered positive.

Results: We included 155 first examinations, 125 for preventive screening (control group), and 30 examinations from patients with lower abdominal pain for ≥ 6 months. Parametropathy with a PI ≥ 2 in ≥ 1 site was found in 96.7% of the pain group, and in 7.2% of the control group (p < 0.001). The diagnostic value of parametropathy for chronic pelvic pain was 96.7% sensitivity and 92.8% specificity. Vaginal ultrasound probe pressure revealed a similar tenderness rate (agreement kappa 0.94-1.00), but with a lower sensitivity of 86.7% and specificity of 92.0%. The prevalence of parametropathy in both groups was higher on the left side (p = 0.03).

Conclusions: Parametropathy, defined as cervical motion tenderness, is a positive sign of chronic pelvic pain syndrome. The cervical motion test to detect parametropathy can be used both as a screening tool and to confirm suspected chronic pelvic pain syndrome. We suggest including this easy-to-perform clinical test in every gynecological examination. By doing so, chronic pelvic pain syndrome will no longer be a diagnosis of exclusion.

Introduction: Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) has been shown to reduce the symptoms of patients with fibromyalgia syndrome (FMS). We tested whether rTMS of the left DLPFC can reduce the main symptoms in FMS and whether TMS induces changes in brain functional and structural connectivity, cortical gray matter volume, and the metabolites/neurotransmitters GABA and combined glutamate/glutamine (Glx).

Methods: Twenty-seven women diagnosed with FMS according to the 2010 ACR criteria were included in a randomized controlled trial. They received either ten sessions of active or sham 10-Hz stimulation over 2 weeks embedded in a longitudinal neuroimaging setup, including one pre-treatment (T1), one post-treatment (T2), and one follow-up (T3) 3 T MRI scan. Pain and pain catastrophizing, depression, daily life/quality of life, and anxiety were assessed using standard questionnaires.

Results: Linear mixed-model analysis of clinical data showed a significant main effect of the main factor time but did not reveal group differences or group-time interactions, indicating a large placebo effect with symptom reduction in both groups. Fractional anisotropy (FA) values of the pontine crossing tract, the sagittal stratum, and the right cingulum in the active rTMS group increased between pre-TMS and the follow-up time points. Subgroup analysis of responders of the treatment group revealed higher functional connectivity between the left DLPFC and the right cerebellum. We did not find evidence for changes in the treatment group in the gray matter of the left DLPFC and for the concentrations of GABA and Glx, but a trend towards decreasing Glx levels for the factor time in all patients could be detected.

Conclusions: While these results may be due to small sample size and short treatment duration, the findings of increased FA after active rTMS and higher functional connectivity between DLPFC and cerebellum in responders should be further explored.

Trial registration: Auswirkungen der nicht-invasiven Neuromodulation auf das Gehirn bei Fibromyalgiepatienten.

Drks-id: DRKS00019051.