BackgroundPrevious studies on serotonin and norepinephrine reuptake inhibitors (SNRIs) such as duloxetine and venlafaxine have demonstrated efficacy in treating persistent idiopathic dentoalveolar pain (PIDP). However, a third‐generation SNRI with favorable tolerability remains understudied in treating PIDP. The study aims to investigate the role of desvenlafaxine in improving PIDP.MethodsClinical data for patients diagnosed with PIDP who received desvenlafaxine treatment (50–150 mg per day) from March 2024 to January 2025 were retrospectively reviewed at our hospital. Through systematic review of electronic medical records, we extracted demographic and baseline pain characteristics, along with the effectiveness and safety of desvenlafaxine during a 3‐month follow‐up assessed by the Numeric Rating Scale‐11 (NRS‐11) scores for pain and adverse effects. Binary logistic regression was used to identify predictors of response.ResultsAmong 103 patients, pain relief was achieved in 90 patients (87.4%), as evidenced by a ≥ 50% reduction in NRS‐11 scores (p < 0.001), while the remaining 13 patients (12.6%) discontinued medications due to insufficient therapeutic efficacy. Binary logistic regression analysis identified shorter pain duration as an independent predictor of a favorable response to desvenlafaxine, with an odds ratio of 1.037 (95% CI = 1.016–1.058, p < 0.001). Adverse events were reported in 15 patients (14.6%), all mild and transient.ConclusionsThe administration of desvenlafaxine serves as an effective and safe therapeutic approach for patients with PIDP. Patients with a short history of PIDP are more likely to benefit from desvenlafaxine treatment.

Background and AimsElectroacupuncture (EA) has been reported to have a therapeutic potential for visceral hypersensitivity. Recent studies have highlighted the crucial role of the duodenum in visceral hypersensitivity, suggesting it as a potential therapeutic target. This study investigates how EA regulates visceral hypersensitivity in the duodenum.MethodWe established a visceral hypersensitivity model in rats by intragastric administration of iodoacetamide. Various parameters were evaluated, including electromyographic recordings in vivo, mesentery afferent nerve spontaneous discharge, mechanical sensitivity, and chemical sensitivity. Western blotting and immunofluorescence were employed to detect the protein expression of nociceptor transient receptor potential vanilloid 1 (TRPV1) and to assess eosinophil infiltration by labeling eosinophil major basic protein (EMBP). We examined whether the effect of EA was mediated by TRPV1, using the agonist capsaicin and the antagonist SB366791. Eosinophils were counted, and their activation and degranulation status were assessed. We explored the impact of eosinophils on the neuron fibers of the intestine.ResultsEA decreased firing of visceral afferent action potentials including spontaneous, mechanosensitive and chemosensitive mesentery afferent discharge, and attenuated visceromotor electromyographic activity. The above effects of EA were reversed by intraperitoneal injection or in vitro enteric nerve administration of TRPV1 agonist capsaicin. EA substantially reduced the area of neuron fibers and the TRPV1 expression. Furthermore, in vitro experiments using primary cell cultures indicated that eosinophils’ degranulation with different doses could stimulate neuron fibers. EA at ST36 was found to reduce both the number of duodenal eosinophil‐positive cells and the levels of their degranulation products.ConclusionThese results suggested that EA at ST36 alleviates visceral hypersensitivity by inhibiting eosinophils degranulation and TRPV1 expression in the duodenum.

Toradol, a potent nonsteroidal anti-inflammatory drug, is widely used for perioperative analgesia, especially in orthopedic surgeries. Postmarketing surveillance is crucial due to its extensive clinical application. This study aimed to investigate adverse events (AEs) associated with Toradol using the FDA Adverse Event Reporting System (FAERS), analyze the association strengths of key AEs, and provide clinical references. FAERS data from 2004 Q1 to 2017 Q4 were analyzed, including reports where Toradol was the primary suspect drug. Disproportionality analyses were conducted using ROR, PRR, BCPNN, and EBGM algorithms to detect safety signals. Among 377 eligible reports, key AEs included immune system disorders (anaphylactic reaction, ROR = 16.28), renal and urinary disorders (oliguria, ROR = 25.57), and gastrointestinal disorders (erosive duodenitis, ROR = 231.08). Notably, 29.86% of reports were from consumers, with a lower proportion from healthcare professionals. Most AEs (73.10%) occurred within 7 days of administration; rare but severe events, including deafness and cardiorespiratory arrest, were also identified. Our findings, derived from hypothesis-generating signal detection analyses, provide real-world safety data on Toradol, highlighting high-risk AEs and reporting biases. Enhanced vigilance and monitoring, especially in high-risk populations, are imperative. However, these signals require confirmation through prospective, controlled studies to establish causality.

To determine the influence of sensitization-associated and neuropathic-like symptoms and clinical features in conditioned pain modulation (CPM) activity in women with episodic or chronic migraine. A cross-sectional study including 70 women with chronic migraine and 70 with episodic migraine was performed. Clinical migraine features (related disability, pain intensity, frequency, and duration) and pain processing variables (sensitization-associated or neuropathic-like symptoms) were evaluated with self-reported outcomes. Pressure pain thresholds (PPTs) at the temporalis muscle, lateral epicondyle, and tibialis anterior were bilaterally assessed. Heat (HPT) and cold (CPT) pain thresholds at the frontalis (V1 area) muscle were also assessed. Subsequently, CPM was evaluated immediately after a 1-min cold-pressor test paradigm on changes obtained in PPTs, HPT, and CPT. No significant group ∗ time interactions after controlling for migraine features, related disability (MIDAS, HIT-6), sensitization-associated (CSI), or neuropathic-like symptoms (S-LANSS) were found for PPTs at the temporalis muscle (Wilk's λ = 0.996, F[1128] = 0.500, p = 0.481, n2p = 0.004, 1 - β = 0.108), lateral epicondyle (Wilk's λ = 0.997, F[1128] = 0.369, p = 0.545, n2p = 0.003, 1 - β = 0.093), and tibialis anterior (Wilk's λ = 0.999, F[1128] = 0.070, p = 0.792, n2p = 0.001, 1 - β = 0.058) as well as CPT (Wilk's λ = 0.991, F[1128] = 1.136, p = 0.288, n2p = 0.009, 1 - β = 0.185) or HPT (Wilk's λ = 0.992, F[1128] = 0.992, p = 0.315, n2p = 0.008, 1 - β = 0.170): no significant changes in PPTs, CPTs, or HPTs were seen after the conditioned stimulus in women with either episodic or chronic migraine. No significant effect of clinical or pain processing outcomes on CPM was seen. This study showed similar CPM activation (lack of) in women with episodic and chronic migraine. Thus, clinical features and the presence of sensitization-associated or neuropathic-like symptoms did not modulate CPM activity in women with migraine.

Pain control remains a cornerstone in endodontic practice, particularly in cases of symptomatic irreversible pulpitis where achieving profound anaesthesia is often challenging. As the inferior alveolar nerve block (IANB) frequently fails to provide profound pulpal anaesthesia, optimizing pain control in such cases requires evidence-based modifications to anaesthetic techniques and the use of supplemental approaches. This narrative review aims to synthesize current evidence on clinical strategies for improving pain management in mandibular molars with symptomatic irreversible pulpitis, with particular emphasis on enhancing the efficacy of IANB and supplemental injection techniques. A narrative review methodology was employed to synthesize clinical trials and systematic reviews published between 1975 and 2025. Evidence indicates that increasing the anaesthetic volume and applying supplemental techniques, including intraligamentary, intraosseous and intrapulpal injections, significantly enhances anaesthesia success. Adjunctive measures such as cryotherapy and temperature modification of anaesthetic solutions further improve pain control. The integration of these methods provides a predictable and multimodal approach to managing endodontic pain in challenging clinical scenarios. Effective pain management in mandibular molars with symptomatic irreversible pulpitis relies on a comprehensive strategy that combines optimized anaesthetic volume and supplemental techniques. Intrapulpal anaesthesia remains essential for achieving pulpal anaesthesia when all other techniques fail. Continued clinical research is essential to refine these approaches and establish standardized protocols for achieving reliable anaesthesia in endodontic practice.

Research highlights the potential role of physical activity (PA) in preventing chronic pain and reducing both acute and persistent pain symptoms. While increasing PA is an evidence-based intervention for chronic pain, the relationship between pain processing and PA remains unclear. This study aimed to investigate associations of both PA and fitness assessments with multiple measures of pain sensitivity, hypothesizing links with both static and dynamic pain sensitivity metrics. Sixty-four healthy adults (30 female) representing both high and low activity levels completed a series of pressure-based quantitative sensory tests (QST), including static measures (pressure pain thresholds [PPTs]) and dynamic measures (temporal summation [TS] and conditioned pain modulation [CPM]). PA was evaluated using the International Physical Activity Questionnaire (IPAQ, self-report) and accelerometry (objective). Cardiorespiratory fitness (CRF) was assessed using the YMCA step test. Correlation and regression analyses were used to evaluate these relationships. Higher PPTs were related to more self-reported moderate-to-vigorous PA, vigorous PA, and total PA; accelerometry vigorous PA; and high CRF (p ≤ 0.01). Self-reported vigorous PA was inversely correlated with TS (p = 0.01), while the other PA or CRF metrics were not significantly associated with either TS or CPM (p ≥ 0.04). CRF or vigorous PA metrics were more consistently related to static pressure QST (PPT) than to dynamic QST (TS and CPM). Our findings in a single cohort mirror the inconsistencies noted across cohorts in the literature, suggesting that PA and CRF exhibit distinct relationships with various QST measures.

To examine the effects of music therapy, inhalation aromatherapy, and their combination on pain intensity, anxiety, and fear in patients undergoing coronary angiography. This randomized controlled trial included 128 patients assigned to four groups: control, music therapy, aromatherapy, and combined music + aromatherapy. Interventions were applied 5-10 min before the procedure and continued during angiography. Visual analog scales for assessing pain (VAS-P), anxiety (VAS-A), and fear (VAS-F), and the State Anxiety Inventory (SAI) were assessed pre- and postprocedure. Data were analyzed using mixed-design ANOVA to examine time, group, and time × group effects, and effect sizes (η 2) were calculated. Significant time × group interactions were found for pain (η 2 = 0.205), fear (η 2 = 0.527), anxiety (η 2 = 0.550), and state anxiety (η 2 = 0.546) (all p < 0.001). All intervention groups showed greater reductions in pain, anxiety, and fear compared with the control group (p < 0.001). No significant differences were observed among the three intervention groups (p > 0.05), although the combined intervention yielded the largest improvements. Music therapy and inhalation aromatherapy reduce pain, anxiety, and fear in patients undergoing coronary angiography effectively and can be recommended as nonpharmacological nursing interventions. Trial Registration: ClinicalTrials.gov.: NCT05622383.

Indwelling nerve catheters are commonly used for postoperative analgesia following limb fracture surgeries. This multicenter, randomized, single-blind, active-controlled parallel trial aimed to compare the novel Tuoren catheter-over-needle assembly with the Contiplex D catheter-through-needle assembly for postoperative pain management. The trial was conducted at three centers in China. Patients undergoing elective limb fracture surgery were randomly assigned (1:1) to either the Tuoren group or the Contiplex D group for postoperative analgesia. The primary outcome was the noninferiority of the Tuoren assembly compared to that of the Contiplex D assembly in terms of the 24-h postoperative analgesia effectiveness rate. Secondary outcomes were patient and surgeon satisfaction, safety, and the time required for puncture and catheter insertion. The rate of local anesthetic leakage and the incidence of catheter kinking and dislodgement during analgesia were also evaluated. Between June 2019 and June 2021, 232 patients were randomized. The 24-h postoperative analgesia effectiveness rate was 99.1% in both groups. After adjusting for surgery types and centers, the difference was 0.06% [-2.36%, 2.49%] with a 95% CI. The lower boundary was above the noninferiority limit of -10%. The insertion time for the Tuoren assembly was significantly shorter compared to that of the Contiplex D assembly. Other outcomes did not show statistical differences. The novel Tuoren assembly was noninferior to the Contiplex D catheter-through-needle assembly in terms of analgesic effectiveness and safety. Chinese Registry of Clinical Trials: ChiCTR1900022980.

Pain assessment disparities across demographic groups pose a significant healthcare challenge, with women, elderly patients, and racial minorities frequently experiencing inadequate treatment. Current pain evaluation relies predominantly on subjective self-reporting scales, which lack objective physiological biomarkers and can be influenced by communication barriers and provider bias, limiting their effectiveness for equitable and precise pain measurement. This study investigates the development and validation of ECG-derived biomarkers for objective pain assessment through machine learning enhanced with explainable artificial intelligence (XAI), establishing a foundation for precision pain management that addresses existing healthcare disparities. We implemented a dual-model machine learning architecture incorporating SHapley Additive exPlanations (SHAP) for transparent pain assessment using ECG biomarkers. The system employs a Random Forest Classifier for binary pain detection (CoVAS = 0 vs. CoVAS > 0) and a Random Forest Regressor for continuous pain intensity estimation (0-100 scale). Comprehensive feature extraction from ECG signals captured time-domain, frequency-domain, and heart rate variability parameters as candidate pain biomarkers. The classification model achieved 85.2% accuracy in distinguishing pain presence from pain-free states. Key validated biomarkers included ECG root mean square (RMS), peak-to-peak amplitude, and heart rate variability metrics. SHAP analysis provided transparent, interpretable insights into biomarker contributions, revealing complex interactions among cardiac parameters that reflect underlying pain physiology and establishing the explainability necessary for clinical trust and adoption. ECG-derived biomarkers analyzed through explainable machine learning offer a pathway toward objective, transparent pain assessment capable of addressing disparities in pain management. This approach identifies reliable physiological pain indicators from routinely collected cardiac signals, potentially enabling precision pain management in clinical settings where comprehensive multimodal monitoring systems are unavailable, thereby supporting more equitable healthcare delivery.

Background: Dezocine is a leading analgesic in China used for relieving moderate to severe pain. Previous studies have characterized its pharmacological properties, demonstrating its role as a partial agonist at both the κ-opioid receptor (KOR) and the μ-opioid receptor (MOR), thereby producing potent antinociceptive effects in acute pain models. However, its efficacy and mechanisms in chronic pain management remained unclear. Methods: Chronic pain models, including chronic neuropathic pain and cancer pain, were employed using chronic constriction injury (CCI) of the sciatic nerve and bone cancer pain (BCP) methodologies, respectively. The assessment of the mechanical allodynia was conducted using a von Frey filament. Results: Dezocine, administered via the intraperitoneal route, alleviated both neuropathic pain and cancer pain in a dose-dependent manner, with ED50 of 1.3 mg/kg and 1.6 mg/kg, respectively. In the CCI model, the analgesic effect of dezocine was significantly inhibited by pretreating with KOR antagonist nor-BNI, MOR antagonist β-FNA, α2-adrenoceptor antagonist yohimbine, and 5-HT2A receptor antagonist altanserin. In the BCP model, dezocine-induced analgesia was markedly suppressed by nor-BNI, β-FNA, and yohimbine but not altanserin. Conclusion: These results suggest that, in neuropathic pain, the analgesic effects of dezocine are mediated through KOR and MOR activation, together with norepinephrine reuptake inhibition (NRI) and serotonin reuptake inhibition. In contrast, in cancer pain, KOR and MOR activation and NRI are involved in mediating the analgesic effect of dezocine. This study, along with previous data, enhances our understanding of the potential clinical utility of dezocine and elucidates its mechanisms of action in chronic pain management.