PAIN®最新文献

{"title":"Investigating the potential of minocycline in reducing brain inflammation in chronic low back pain: a randomized, placebo-controlled mechanistic clinical trial.","authors":"Mehrbod Mohammadian,Erin J Morrissey,Paulina C Knight,Ludovica Brusaferri,Minhae Kim,Nikolaos Efthimiou,Jennifer P Murphy,Zeynab Alshelh,Grace Grmek,Jack H Schnieders,Courtney A Chane,Angelica Sandström,Ciprian Catana,Jodi M Gilman,Joseph J Locascio,Robert R Edwards,Yi Zhang,Vitaly Napadow,Marco L Loggia","doi":"10.1097/j.pain.0000000000003543","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003543","url":null,"abstract":"Our group has shown that translocator protein (TSPO) levels, a putative marker of neuroinflammation, are increased in the brain and spinal cord of patients with chronic low back pain (cLBP). Whether neuroinflammation might be a therapeutic target for this condition is unknown. In this phase II double-blind, placebo-controlled, randomized clinical trial, we sought to evaluate whether the tetracycline antibiotic minocycline, which is commonly used as a glial inhibitor in preclinical models, has an effect on brain TSPO levels in adults with cLBP. Participants randomly received 100-mg minocycline or placebo, once a day for 2 weeks. The primary outcome was the change (pretreatment vs posttreatment) in thalamic TSPO levels, measured using [11C]PBR28 positron emission tomography signal (standardized uptake value ratio) and analyzed with a mixed effect model. Secondary outcome measures included the change in Brief Pain Inventory, severity subscore. Among 60 enrolled participants, 48 completed the trial. Of these, 25 received minocycline (age [years], mean ± SD: 44.6 ± 16.9; 9 female), and 23 received placebo (49 ± 17.1; 9 female). The mean thalamic positron emission tomography standard uptake value ratio was very stable across visits in both groups, with no significant group-by-time interaction (P = 0.956). Similarly, both groups demonstrated a comparable decrease over time in Brief Pain Inventory severity scores (P = 0.018) and no significant group-by-time interaction (P = 0.329). Our results suggest that minocycline, at the tested regimen, may neither reduce brain TSPO levels nor have clinically meaningful effects on clinical pain in patients with cLBP.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"312 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Somatosensory profiling to differentiate distinct painful diseases of the pancreas-a quantitative sensory testing case-control study.","authors":"Philipp Göltl, Paul Merz, Alexander Schneider, Matthias P Ebert, Michael Hirth, Walter Magerl","doi":"10.1097/j.pain.0000000000003601","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003601","url":null,"abstract":"<p><strong>Abstract: </strong>Mechanisms of pancreatic pain are insufficiently understood, and quantitative sensory testing (QST) may help to identify the underlying mechanisms. Accordingly, this study assessed comprehensive somatosensory profiles encompassing nociceptive and nonnociceptive parameters in 70 patients with distinct pancreatic diseases, namely acute (n = 23), chronic (n = 20), or autoimmune pancreatitis (n = 10) and pancreatic cancer (n = 17) and compared it with 30 healthy control subjects by standardized QST (protocol of the German research network on neuropathic pain). Patients with pancreatic diseases presented significant somatosensory deficits in all thermal and tactile detection and pain thresholds in the pancreatic viscerotome (Th10), when compared with a remote control area (dermatome C5) or reference data of matched healthy controls (P < 0.05-P < 0.0001). Unaltered vibration detection emphasizes the strictly regional character of losses. Loss of sensitivity paralleled the occurrence of paradoxical heat sensation (Th10 vs C5; P < 0.05), an indicator of thermal integration deficit. Punctate hyperalgesia or pain to light touch, the hallmark signs of spinal central sensitization were mostly absent and pain summation remained unchanged (P > 0.05). Stratification of patients revealed that somatosensory deficits were significantly more pronounced in acute compared with chronic pancreatitis (eg, cold and warm detection thresholds: -2.19 ± 1.42 vs -1.10 ± 1.23 and -1.30 ± 1.68 vs -0.11 ± 1.80 z-values; P < 0.05 each). Notably, blunt pressure hyperalgesia, the only somatosensory parameter exhibiting significant gain compared with the patients' remote C5 segment, was a frequent finding only in acute, but not in chronic pancreatitis. The somatosensory phenotype of patients with distinct pancreatic disorders was characterized by a wide array of sensory losses being most severe in acute pancreatitis.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ribosome profiling reveals that post-transcriptional control of Nalf1 by heterogeneous nuclear ribonucleoprotein L is required for paclitaxel-induced neuropathic pain.","authors":"June Bryan de la Peña, Guadalupe García, Zachary T Campbell","doi":"10.1097/j.pain.0000000000003577","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003577","url":null,"abstract":"<p><strong>Abstract: </strong>Sensory neurons are integral to the genesis and maintenance of neuropathic pain. The molecular mechanisms that mediate long-lived changes in their excitability are unclear. Here, we leverage functional genomics approaches to survey changes in RNA abundance and translation in dorsal root ganglion neurons from a mouse model of paclitaxel-induced neuropathic pain. We focus specifically on females as paclitaxel is a first-line therapy for breast cancer. The sequencing data indicate that substantially more changes occur at the level of translation (n = 404) than transcription and decay (n = 109). We discovered that a core subunit of the sodium leak channel (NALCN) channel, auxiliary factor 1 (NALF1), is preferentially translated in response to paclitaxel. This effect is mediated by the RNA-binding protein heterogeneous nuclear ribonucleoprotein L (HNRNP L). Heterogeneous nuclear ribonucleoprotein L binds a 14 base CA-rich element (CARE) in the Nalf1 3' untranslated region (3'UTR). Genetic elimination of either HNRNP L, the Nalf1 CARE motif, or the pore-forming subunit of the nonselective NALCN diminishes pain amplification in vivo. Collectively, these results illustrate that an element situated in a 3'UTR is required for neuropathic pain in female mice.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"I feel your pain: higher empathy is associated with higher posterior default mode network activity.","authors":"Valeria Oliva, Gabriel Riegner, Jon Dean, Lora A Khatib, Alessandro Allen, Daniel Barrows, Conan Chen, Richard Fuentes, Aaron Jacobson, Carolina Lopez, Dwayne Mosbey, Mikaila Reyes, Jacob Ross, Alexandra Uvarova, Thomas Liu, William Mobley, Fadel Zeidan","doi":"10.1097/j.pain.0000000000003434","DOIUrl":"10.1097/j.pain.0000000000003434","url":null,"abstract":"<p><strong>Abstract: </strong>Empathy is characterized as the ability to share one's experience and is associated with altruism. Previous work using blood oxygen level-dependent (BOLD) functional MRI (fMRI) has found that empathy is associated with greater activation in brain mechanisms supporting mentalizing (temporoparietal junction), salience (anterior cingulate cortex; insula), and self-reference (medial prefrontal cortex; precuneus). However, BOLD fMRI has some limitations that may not reliably capture the tonic experience of empathy. To address this, the present study used a perfusion-based arterial spin labeling fMRI approach that provides direct a quantifiable measurement of cerebral blood flow (1 mL/100 g tissue/min) and is less susceptible to low-frequency fluctuations and empathy-based \"carry-over\" effects that may be introduced by BOLD fMRI-based block designs. Twenty-nine healthy females (mean age = 29 years) were administered noxious heat (48°C; left forearm) during arterial spin labeling fMRI. In the next 2 fMRI scans, female volunteers viewed a stranger (laboratory technician) and their romantic partner, respectively, receive pain-evoking heat (48°C; left forearm) in real-time and positioned proximal to the scanner during fMRI acquisition. Visual analog scale (0 = \"not unpleasant\"; 10 = \"most unpleasant sensation imaginable\") empathy ratings were collected after each condition. There was significantly ( P = 0.01) higher empathy while viewing a romantic partner in pain and greater cerebral blood flow in the right temporoparietal junction, amygdala, anterior insula, orbitofrontal cortex, and precuneus when compared with the stranger. Higher empathy was associated with greater precuneus and primary visual cortical activation. The present findings indicate that brain mechanisms supporting the embodiment of another's experience is associated with higher empathy.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"e60-e67"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Care trajectories for musculoskeletal disorders following a new episode of low back pain.","authors":"Pierre Dagenais, Mireille Courteau, Josiane Courteau, Gilles Martel, Alain Vanasse","doi":"10.1097/j.pain.0000000000003409","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003409","url":null,"abstract":"<p><strong>Abstract: </strong>This study explored diverse care trajectories (CTs) for low back pain (LBP) and other musculoskeletal disorders (MSDs), over a 5-year period following a first episode of LBP. Based on Quebec's administrative health data from 2007 to 2011, this longitudinal cohort study involved 12,608 adults seeking health care for LBP. Using a new multidimensional state sequence analysis, we identified 6 distinct types of CTs. The most prevalent types 1, 2, and 3 (comprising 79.2%, 18.0%, and 21.7% of the cohort, respectively) exhibit rapid recovery and similar patterns of healthcare use over 5 years but differing in initial diagnoses: nonspecific LBP in type 1, trauma-related LBP in type 2 (mostly younger men and highest initial emergency consultation), and specific LBP in type 3. Types 4 to 6, representing smaller groups, show high healthcare utilization with comparable mixed LBP diagnoses at entry but distinctive subsequent care use patterns. Patients in types 4 and 6 (mainly older age groups and women) sought care for other MSDs from general practitioners or specialists, while middle-aged patients in type 5 experienced persistent nonspecific LBP with frequent general practitioner consultations over 5 years. The CTs typology revealed several key areas for improvement in nonpharmacological interventions, including the need to address possible inappropriate medical imaging and invasive interventions for older women with MSDs and the lack of ambulatory care access for younger patients with trauma-related LBP. Finally, results clearly highlighted poor access to rehabilitation physicians and rehabilitation services for all patients suffering from LBP and MSDs.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"166 4","pages":"835-846"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights on naproxen's role in sciatica: a discussion on efficacy and risk factors.","authors":"Yu-Pin Huang, Cheng-Wei Lu","doi":"10.1097/j.pain.0000000000003501","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003501","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"166 4","pages":"957-958"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Huang and Lu.","authors":"Lars Grøvle, Eivind Hasvik, René Holst, Anders Sætre, Jens Ivar Brox, Ståle Mathiassen, Kjersti Myhre, Thor Einar Holmgard, Anne Julsrud Haugen","doi":"10.1097/j.pain.0000000000003502","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003502","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"166 4","pages":"958-960"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Na V 1.8/Na V 1.9 double deletion mildly affects acute pain responses in mice.","authors":"Marta Alves-Simões, Laura Teege, Cecilia Tomni, Martha Lürkens, Annika Schmidt, Federico Iseppon, Queensta Millet, Samuel Kühs, Istvan Katona, Joachim Weis, Stefan H Heinemann, Christian A Hübner, John Wood, Enrico Leipold, Ingo Kurth, Natja Haag","doi":"10.1097/j.pain.0000000000003411","DOIUrl":"10.1097/j.pain.0000000000003411","url":null,"abstract":"<p><strong>Abstract: </strong>The 2 tetrodotoxin-resistant (TTXr) voltage-gated sodium channel subtypes Na V 1.8 and Na V 1.9 are important for peripheral pain signaling. As determinants of sensory neuron excitability, they are essential for the initial transduction of sensory stimuli, the electrogenesis of the action potential, and the release of neurotransmitters from sensory neuron terminals. Na V 1.8 and Na V 1.9, which are encoded by SCN10A and SCN11A , respectively, are predominantly expressed in pain-sensitive (nociceptive) neurons localized in the dorsal root ganglia (DRG) along the spinal cord and in the trigeminal ganglia. Mutations in these genes cause various pain disorders in humans. Gain-of-function missense variants in SCN10A result in small fiber neuropathy, while distinct SCN11A mutations cause, i. a., congenital insensitivity to pain, episodic pain, painful neuropathy, and cold-induced pain. To determine the impact of loss-of-function of both channels, we generated Na V 1.8/Na V 1.9 double knockout (DKO) mice using clustered regularly interspaced short palindromic repeats/Cas-mediated gene editing to achieve simultaneous gene disruption. Successful knockout of both channels was verified by whole-cell recordings demonstrating the absence of Na V 1.8- and Na V 1.9-mediated Na + currents in Na V 1.8/Na V 1.9 DKO DRG neurons. Global RNA sequencing identified significant deregulation of C-LTMR marker genes as well as of pain-modulating neuropeptides in Na V 1.8/Na V 1.9 DKO DRG neurons, which fits to the overall only moderately impaired acute pain behavior observed in DKO mice. Besides addressing the function of both sodium channels in pain perception, we further demonstrate that the null-background is a very valuable tool for investigations on the functional properties of individual human disease-causing variants in Na V 1.8 or Na V 1.9 in their native physiological environment.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"773-792"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in the clinical presentation of chronic whiplash-associated disorders and nontraumatic neck pain: a systematic review and meta-analysis.","authors":"Junze Chen, Scott F Farrell, Wanyun Irene Huang, Barbara Cagnie, Carlos Murillo, Michele Sterling","doi":"10.1097/j.pain.0000000000003554","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003554","url":null,"abstract":"<p><strong>Abstract: </strong>Health outcomes may be worse for individuals with whiplash-associated disorders (WAD) compared to nontraumatic neck pain (NTNP), and clinical characteristics may differ. This systematic review examined evidence comparing WAD and NTNP in terms of pain, disability, psychological status, quality of life, measures of nociceptive processing, movement, sensorimotor, and muscle function. Studies were identified through electronic database searches and included after screening against predefined eligibility criteria. Standardized mean differences (SMD) or mean differences (MD) and 95% confidence intervals (CI) were calculated. Associations between MDs with demographics and study characteristics were explored using meta-regression. Certainty of evidence was assessed using Grades of Recommendation, Assessment, Development, and Evaluation. Sixty-one studies were eligible with 45 included in meta-analysis. Individuals with WAD reported clinically relevant higher disability (100-point Neck Disability Index MD [95% CI] 11.15 [8.63, 13.68]), greater remote cold sensitivity (SMD 0.89 [0.57, 1.21]), lower quality of life (SMD -0.96 [-1.77, -0.16]), greater depression (SMD 0.60 [0.27, 0.93]), greater local (SMD -0.56 [-1.00, -0.13]) and remote (SMD -0.50 [-0.81, -0.19]) pressure sensitivity, less cervical flexion (MD -5.30° [-7.44, -3.16]) and extension (MD -5.43° [-9.31, -1.55]), higher pain intensity (100-point numerical rating scale: MD 8.15 [5.80, 10.50]), and greater kinesiophobia (SMD 0.35 [0.11, 0.59]). No between-group differences were found for dizziness symptoms, stress, anxiety, balance, and local cold sensitivity. Meta-regression indicated that disability differences were negatively associated with age (R2 = 29.6%, P = 0.006). Certainty of evidence was mostly moderate. Individuals with chronic WAD have a worse clinical presentation compared to those with chronic NTNP, which has implications for patient assessment and management.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPV1 is the burner.","authors":"Annekathrin Alpes, Sofia Malek, Ralf Baron","doi":"10.1097/j.pain.0000000000003542","DOIUrl":"10.1097/j.pain.0000000000003542","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"717-718"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}