Journal of Pain Research最新文献

Background: Electrical detection threshold (EDT) and electrical pain threshold (EPT) measured via PainVision^® offer a non-invasive method to objectively assess sensory function, directly targeting specific nerve fibers. This study aimed to evaluate the reliability and preliminary validity of EDT and EPT across different anatomical sites in healthy young adults.

Patients and methods: Forty-six participants underwent EDT and EPT assessments at four sites across two sessions separated by 2-3 days. Pain intensity at the medial forearm was recorded using the visual analogue scale (VAS) following 30-second electrical stimulation. Intraclass correlation coefficients (ICC) and minimal detectable changes (MDC) were calculated, and correlations between EPT and VAS were analyzed.

Results: EDT and EPT showed good to excellent reliability (ICC 0.75-0.95 and 0.83-0.99, respectively). MDC ranged from 1.26-1.81 for EDT and 1.18-1.99 for EPT. EPT was negatively correlated with VAS scores (r = -0.746, 95% CI [-0.852, -0.582]).

Conclusion: EDT and EPT measurements using PainVision^® demonstrated robust reliability and preliminary validity in healthy young adults, highlighting their potential as a standardized, non-invasive tool for assessing electrical sensory thresholds. This study provides baseline data for future research in clinical populations.

Background: Pulsed radiofrequency (PRF) is used for refractory neuropathic pain, yet its mechanisms remain incompletely defined. The dorsal root ganglion (DRG) and peripheral nerves (eg, sciatic nerve) are common targets and key nodes in nociceptive transmission and neuro-immune crosstalk. Compared with implantable electrical neuromodulation (SCS/PNS), PRF provides non-invasive, percutaneous neuromodulation. Epigenetic regulation after PRF is plausible because chronic pain causes transcriptional modifications and electrical neuromodulation may influence chromatin-based gene control.

Objective: To summarize preclinical evidence on epigenetic and molecular changes after PRF applied to the DRG or peripheral nerves.

Methods: PubMed, Embase, and Scopus were searched (PRISMA-S); synthesis followed SWiM. Studies assessed direct epigenetic modifications and/or gene/protein expression changes after PRF at DRG or peripheral nerve targets. Risk of bias was evaluated using the JBI checklist for animal studies.

Results: Seventeen rodent studies were included. One study reported a direct epigenetic modification, showing that PRF reversed complete Freund's adjuvant (CFA)-induced histone H3/H4 hypoacetylation at the Kcc2 locus, restoring KCC2 expression. Other studies linked PRF to attenuation of microglial/MAPK signaling, modulation of neurotrophic mediators, downregulation of pro-inflammatory cytokines, and normalization of sensory neuron excitability markers across DRG, sciatic nerve, and spinal dorsal horn tissue. Target-specific trends emerged: DRG PRF more consistently attenuated spinal microglial/MAPK signaling, whereas sciatic PRF emphasized normalization of DRG channels/neuropeptides. No human studies and no circulating epigenetic biomarkers were identified.

Conclusion: Preclinical data support a non-destructive PRF mechanism involving dampening of neuro-immune signaling and restoration of inhibitory tone. Direct epigenetic evidence remains limited (single study) and absent in humans. Priorities include standardized PRF parameter reporting, time-course and multi-omic profiling beyond Kcc2, and prospective clinical studies incorporating molecular endpoints and circulating epigenetic readouts.

Object: Previous studies have found that circulating inflammatory proteins may play an essential role in the occurrence and development of neuropathic pain. However, the majority of existing evidence is derived from observational studies, which are prone to confounding factors and reverse causality, and the inflammatory profiles associated with different types of neuropathic pain remain poorly understood. Consequently, more robust methodologies are urgently required to elucidate the causal relationships between these variables. Therefore, a bidirectional Mendelian randomization analysis was performed to assess the causal relationship between inflammatory proteins and neuropathic pain, specifically focusing on neuralgia and neuritis, including glossopharyngeal neuralgia, phantom limb syndrome with pain,small fiber neuropathy, and unspecified neuralgia.

Methods: Instrumental variables were obtained from publicly available genome-wide association study datasets. Five different models were used for MR Analysis, including the inverse variance weighted model, weighted median estimation model, weighted model-based method, MR-Egger regression model and simple mode. Heterogeneity in the results was assessed using the Cochrane Q test. Horizontal pleiotropy was evaluated through the MR-Egger intercept test and the MR pleiotropy residual sum and outliers test. Sensitivity analysis was conducted through leave-one-out analysis.

Results: The results suggest a genetically predicted potential association between fractalkine levels (CX3CL1) (OR=0.182; 95CI=0.048-0.691; p=0.012), signaling lymphocytic activation molecule levels (SLAMF1) (OR=0.295; 95CI=0.099-0.879; p=0.028), tumor necrosis factor levels (TNF) (OR=0.281; 95CI=0.085-0.931; p=0.038), matrix metalloproteinase-1 (MMP-1) (OR=3.399; 95CI=1.140-10.133; p=0.028), and tumor necrosis factor receptor superfamily member 9 levels (TNFRSF9) (OR=0.281; 95CI=0.085-0.931; p=0.038) with the risk of glossopharyngeal nerve disease. In addition, we identified FGF5, FGF21, FGF23, Osteoprotegerin, CD40LG, IL-12B, IL-20RA, IL-24, CCL8, CCL28, CD244, CCL3, OSM, and SIRT2 as associated with the occurrence of the other three types of neuropathic pain.The sensitivity analysis revealed no heterogeneity or levels of pleiotropy.

Conclusion: Our Mendelian randomization analysis revealed several genetically predicted associations between circulating inflammatory proteins and the risk of neuropathic pain subtypes. These findings indicate that immune- and inflammation-related pathways may be implicated in the pathogenesis of neuropathic pain, although further functional and clinical investigations are required to validate these associations and elucidate the underlying mechanisms.

Background: Endometriosis (EMS) is characterized by pain symptoms that seriously affect patients' quality of life. Gut microbiome-related metabolites (GMRM) play an important role in the process of EMS. However, the role of GMRM in endometrial stem cells and EMS-related pain remains unclear.

Methods: An untargeted metabolomics approach was employed to analyze the fecal samples of 10 healthy individuals (heal), 11 EMS patients without dysmenorrhea (pless), and 14 EMS patients with dysmenorrhea (pain). The impact of potential key metabolite sakuranin on EMS-related pain was further investigated in vitro and in vivo.

Results: We identified 33 metabolites that were commonly changed in the painful group compared to the health and pless groups, and these metabolites were associated with differential microorganisms. Among them, sakuranin was downregulated in the painful group and exhibited a notably inverse correlation with the degree of pain. ROC curve revealed that sakuranin had a relatively high predictive value for EMS-related pain (AUC=0.8027). Functionally, sakuranin inhibited differentiation, migration, and inflammatory cytokine production, and decreased the expression of VEGF and ALCAM in SUSD2-positive primary endometrial cells. In EMS mice, sakuranin suppressed ectopic lesion growth, reduced inflammation, modulated angiogenesis and proliferation markers (VEGF, ALCAM, Ki-67), and regulated sympathetic and sensory nerve markers, resulting in alleviated pain behaviors.

Conclusion: We delineated the metabolic landscape related to EMS-related pain and uncovered that sakuranin has the potential to inhibit the growth of EMS and alleviate EMS-related pain. This finding offers therapeutic strategies of sakuranin in alleviating the pain symptoms associated with EMS.

Background: Radiofrequency ablation (RFA) is widely used as an interventional treatment for chronic low back pain; however, its clinical effectiveness across different pain generators remains uncertain, particularly when evaluated in rigorously controlled trials.

Objective: To systematically review randomized controlled trials assessing the effectiveness of RFA for chronic low back pain, stratified by pain generator and radiofrequency technique.

Methods: A systematic search of PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov was conducted to identify randomized controlled trials evaluating RFA for chronic low back pain. Trials employing sham or active comparator interventions were included. Study selection, data extraction, and risk of bias assessment were performed independently by two reviewers.

Results: Six randomized controlled trials involving different pain generators were included. For discogenic low back pain, RFA of the ramus communicans did not demonstrate superiority over sham treatment, with pain reduction observed over time in both groups. Similarly, for facet joint pain, medial branch RFA was not superior to sham procedures within the studied follow-up period. For sacroiliac joint pain, results were heterogeneous. Sham-controlled trials evaluating conventional lateral branch RFA did not demonstrate a specific treatment effect, whereas studies employing alternative techniques, including strip-lesion, capsular, or cooled RFA, were associated with greater and more sustained pain reduction, with statistically significant between-group differences reported at up to 12 months in selected trials.

Conclusion: Based on a limited number of randomized controlled trials, RFA does not consistently demonstrate superiority over sham treatment for discogenic or facet joint-related chronic low back pain. For sacroiliac joint pain, selected RFA techniques may offer benefit in appropriately selected patients; however, conclusions remain constrained by heterogeneity and small sample sizes. Further high-quality, sham-controlled trials are required before definitive clinical recommendations can be made.

Purpose: Knee osteoarthritis (KOA) is a chronic degenerative joint disease causing pain, stiffness, and dysfunction. Acupuncture is widely used in the management of KOA, but its metabolic mechanisms remain unclear. In this study, we evaluated the clinical efficacy of acupuncture in KOA and explored its potential mechanisms via serum lipidomics.

Patients and methods: Fifty-eight KOA patients received standardized acupuncture at Dubi (ST35), Neixiyan (EX-LE4), Zusanli (ST36), Yanglingquan (GB34), Xuehai (SP10), Liangqiu (ST34), contralateral Quchi (LI11), Taixi (KI3), and Sanyinjiao (SP6), six sessions per week for four consecutive weeks; 22 healthy subjects served as controls. We assessed clinical efficacy using WOMAC and VAS scores, analyzed serum lipid profiles before and after treatment with LC-MS/MS and performed KEGG pathway enrichment.

Results: After treatment, WOMAC and VAS scores significantly decreased (P < 0.05). Lipidomics identified 538 differential metabolites between KOA patients and controls, primarily involved autophagy and glycerolipid metabolism. 218 metabolites changed after acupuncture, including PE (20:1_18:1), LPC (16:0/0:0), and LPE (0:0/18:0), related to neuroactive ligand-receptor interaction and glycerophospholipid metabolism. 68 lipids showed reversed trends post-treatment.

Conclusion: Acupuncture significantly improved pain and function in KOA and modulated serum lipid metabolism. Regulation of phosphatidylethanolamine (PE), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), and triglycerides (TG), together with enrichment of related pathways, suggests that acupuncture restores lipid homeostasis and alleviates inflammation, supporting its metabolic therapeutic role in KOA.

Objective: This study aimed to investigate the effects of different lung ventilation strategies on cerebral oxygen saturation (rSO₂) during one-lung ventilation (OLV) in neonates.

Methods: A total of 50 neonates scheduled for elective OLV between October 2022 and April 2024 were enrolled and randomly assigned to either the control group (Group C) or the study group (Group S). In Group S, the respiratory rate was adjusted to maintain end-tidal carbon dioxide (PETCO₂) levels between 45-55 mmHg at 30 minutes of OLV (T3) and subsequently restored to normal levels (35-45 mmHg) at 45 minutes of OLV (T4). Lung recruitment maneuvers were applied. In Group C, PETCO₂ was maintained within the normal range throughout the procedure. Oxygen saturation (SpO₂) and rSO₂, along with additional physiological parameters, were recorded at five time points: before OLV (T1), 15 minutes after OLV initiation (T2), T3, T4, and 60 minutes after OLV initiation (T5). Arterial blood samples were collected for blood gas analysis.

Results: In both groups, rSO₂ levels significantly decreased during OLV compared to baseline (T1) (p < 0.05). However, at T3, rSO₂ was significantly higher in Group S compared to Group C. Comparisons within the group indicated that rSO₂ in Group S at T3 was significantly higher than at T5. Lung compliance was superior in Group S compared to Group C at T5. Furthermore, lung compliance in both groups decreased at T2 when compared to T1 (p < 0.05).

Conclusion: Despite maintaining SpO₂ within the normal range, rSO₂ declined during OLV in neonates. The application of permissive hypercapnia during OLV improved rSO₂ within a certain range. Routine perioperative monitoring of rSO₂ in neonates undergoing OLV may facilitate early detection of cerebral oxygenation changes, contributing to neuroprotection.

Introduction: Herpes zoster (HZ) can adversely influence patients' quality of life and sometimes it can develop postherpetic neuralgia (PHN). To date, it remains challenging manage well using currently available therapies. Tender point infiltration (TPI) might have the potential to be an analgesic therapy for acute and subacute HZ pain. However, current evidence remains insufficient. Therefore, the purpose of this protocol is to design a study to: 1) evaluate the analgesia efficacy and safety of TPI for acute and subacute HZ; 2) to explore the positive predictors of TPI for prevention of PHN.

Methods and analysis: This study is designed as a randomized, prospective, multicenter, blinded endpoint, open-label controlled trial including a 12-month follow-up period. 176 qualified participants will be randomly split into the standard group or TPI group in a ratio of 1:1. Primary outcome will be the presence of PHN 12 months posttreatment. Secondary outcomes include the presence of PHN at month 3 and month 6 posttreatment. Visual Analogue Scales (VAS) for assessment of pain, consumption of oral analgesia drugs, patient satisfaction scores on the 5-point Likert scale, patients' quality of life scored on the WHOQOL-BREF at day 1, week 2, month 1, month 3, month 6 and month 12, proportion of patients receiving repeated TPIs and block points each time for TPI group. Multivariable logistic analyses will be performed to identify predictive factors for the prevention of PHN at month 12 after treatment. Safety evaluation will be determined by adverse events during the trial.

Purpose: Currently, there are limited effective treatment strategies available for refractory chemotherapy-induced peripheral neuropathy (CIPN). Lumbar sympathicolysis is a minimally invasive therapy and may offer an option for CIPN. This single-center, prospective, observational study aimed to evaluate the efficacy and safety of CT-guided lumbar sympathicolysis in alleviating multiple symptoms of refractory CIPN in the lower extremities.

Methods: This single-arm study conducted at Henan Cancer Hospital from September 2022 to July 2024,twenty-five patients with refractory CIPN in both lower extremities received CT-guided lumbar sympathicolysis. The effectiveness of the treatment for pain, numbness, cold sensation, and dyskinesia was evaluated using a Numerical Rating Scale (NRS) at day 3, one month, and three months following treatment. Treatment response was defined as an NRS score reduction of ≥30%. Changes in NRS scores over time were analyzed using generalized estimating equations. Any adverse effects related to the treatment were recorded.

Results: Postoperative NRS scores for pain, numbness, cold sensation, and dyskinesia at 3 days, 1 month, and 3 months were significantly lower than these assessed before the treatment. The pain improvement assessed with NRS scores was reported to be 61.1% at 3 days, 55.5% at 1 month, and 55.5% at 3 months by patients (n=18). The numbness improvement was 24.0% at day 3, 16.0% at 1 month, and 16.0% at 3 months (n=25). Cold sensation improvement (n=21) was 71.4%, 57.1%, and 52.4% at day 3, 1 month, and 3 months (n=21), respectively. The decreased dyskinesia sensation was reported by 50.0% at day 3 and 1 month, and 57.1% at 3 months (n=14). Overall, all symptoms were decreased by 68% at day 3, 64% at 1 month, and 60% at 3 months.

Conclusion: The CT-guided lumbar sympathicolysis may offer substantial symptom relief for CIPN in the lower extremities without clinically significant adverse effects. These preliminary findings warrant further validation in larger, controlled studies.

Background: Acupotomy is a minimally invasive procedure integrating traditional Chinese medicine principles with modern anatomy. While effective for low back pain in lumbar disc herniation (LDH), its efficacy for radicular symptoms from nerve root compression remains limited. A novel technique, intraspinal acupotomy decompression, targets the meningovertebral ligaments (MVL) to alleviate neural compression. This study aims to evaluate and compare the clinical efficacy of intraspinal decompression, extraspinal decompression, and their combination for LDH.

Methods: This is a three-arm, randomized, single-center, single-blind (assessor-blinded) controlled trial. Due to the nature of the interventions, participants and practitioners cannot be blinded. The planned sample size is 210 eligible LDH patients aged 20-85, who will be randomly allocated to one of three groups (n=70 each): the extraspinal acupotomy group, the intraspinal acupotomy group, or the combined group. All groups will receive one treatment session per week for four weeks. The primary outcomes are pain intensity (Visual Analogue Scale, VAS) and lumbar function (Japanese Orthopaedic Association Score, JOA), assessed at baseline, 4 weeks (post-treatment), and 8 weeks (primary endpoint). The secondary outcomes include quality of life (36-Item Short Form Health Survey, SF-36) and adverse events, assessed at 8 weeks.

Conclusion: This study will provide high-quality evidence on the efficacy of a novel intraspinal acupotomy technique. The findings will help determine the optimal acupotomy decompression strategy for LDH, potentially offering a more effective minimally invasive option for patients with radicular symptoms.

Trial registration: International Traditional Medicine Clinical Trial Registry (ITMCTR2025001872). Registered on 25 September 2025.