Search Results (229)

Background/Objectives: Patients with breast cancer undergoing chemotherapy with taxanes or platin derivates often develop peripheral neuropathy (CIPN). Higher-grade CIPN generally affects the patient’s quality of life. Because the treatment options for CIPN are limited, early diagnosis is desirable to allow for timely modifications of the treatment. This may be facilitated with scoring tools that are ideally usable by the patients. A prospective study suggested that a recently developed self-assessment tool might be able to reveal the difference between the absence of CIPN and higher-grade CIPN. When CIPN has reached an advanced grade, alteration of the chemotherapy regimen may have only a limited effect. Therefore, it is important to know whether the new scoring tool can identify CIPN even when it is still mild. The current trial (NCT07604441) aims to identify the optimal cutoff point value for detecting mild CIPN. Given the limited sample size, the derived cutoff will be considered preliminary and will require validation in a larger independent cohort. Methods: The NEURO-BREAC-02 trial aims to identify the optimal cutoff point value of the new tool to distinguish between absent and mild CIPN after treatment with taxanes for breast cancer. Scores ranging between 0 and 44 points are reported via self-assessment supported by a neuropathy tracker. Secondly, the satisfaction of participants with the self-assessment tool is evaluated. Twenty-six participants (19 with mild CIPN and 7 without CIPN) are required, and 28 must be enrolled. Conclusions: The outcomes of the NEURO-BREAC-02 trial are considered crucial for the creation of a self-assessment tool to identify mild CIPN in patients with breast cancer and are a necessary addition to the preceding NEURO-BREAC study. Full article

Background: Cancer pain affects approximately 44.5% of all patients with malignancy and up to 55–65% of those with advanced or metastatic disease; a substantial proportion remain inadequately controlled with conventional pharmacological approaches alone. Peripheral nerve stimulation (PNS), a minimally invasive neuromodulatory strategy, has emerged as a potential opioid-sparing analgesic option for the perioperative management of oncologic surgical patients. Objectives: This narrative review synthesizes current evidence on the application, mechanisms, clinical efficacy, safety, and integration of temporary and permanent PNS systems in cancer patients, with specific focus on cancer-specific pain syndromes, key clinical studies, opioid-sparing immunological implications, evidence quality, and directions for future research. Methods: As a narrative review, this work was structured in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA) to ensure methodological transparency. A focused, non-systematic literature search of PubMed/MEDLINE, Embase, and the Cochrane Library was performed from database inception through March 2026, supplemented by hand-searching of reference lists and targeted retrieval of clinical practice guidelines. Sources were selected on the basis of relevance to PNS or closely analogous peripheral neurostimulation modalities in oncologic, perioperative, or chronic pain contexts. Evidence was synthesized narratively, with each cited study graded using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2011 Levels of Evidence framework to enable transparent calibration of confidence. Results: Available preliminary and largely extrapolated evidence supports PNS as a promising but not yet established useful adjunct in oncologic perioperative care; because cancer-specific data rest substantially on a single pilot study (n = 12), one retrospective review (n = 15), and extrapolation from non-cancer populations, these conclusions should be regarded as hypothesis-generating. Randomized controlled trial data from non-cancer cohorts demonstrate opioid consumption reductions of approximately 80–90% in the PAINfRE trial, while the post-amputation trial demonstrated ≥50% pain-relief responder rates and reductions in pain interference, with clinically meaningful improvements in pain and function. Oncologic-specific pilot and retrospective evidence confirms feasibility and a 58–67% success rate across diverse cancer pain subtypes. Conclusions: The opioid-sparing properties of PNS carry additional biological plausibility for preserving perioperative antitumor immune function. High-quality prospective trials specifically designed for oncologic surgical populations remain needed to establish evidence-based recommendations. Full article

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, disabling toxicity with no validated biomarkers. MRI-based functional neuroimaging could offer insight into central pain processing and may reveal reproducible brain signatures of CIPN. Methods: Following PRISMA 2020 (PROSPERO: CRD420251132102), we systematically reviewed whole-brain MRI studies in adult cancer patients with CIPN. Eligible MRI techniques included task-based fMRI, resting-state fMRI, perfusion MRI, and structural MRI. Data were synthesized through voxelwise activation likelihood estimation (ALE), systems-level region-of-interest (ROI) mapping, and proportion meta-analysis of regional involvement. Results: Of 2488 screened records, five observational studies were included. The voxelwise ALE analysis did not identify clusters surviving correction, but dispersed foci appeared within the default mode network (DMN), prefrontal executive cortex, and primary sensorimotor regions, suggesting the engagement of these pain-processing networks. ROI synthesis confirmed consistent alterations in the DMN and executive prefrontal and sensorimotor cortices in CIPN patients compared with controls, while the brainstem/periaqueductal gray and cerebellum were rarely implicated. Proportion meta-analysis further quantified these differences: CIPN patients showed altered involvement in 30% (95% CI 0.16–0.48) of contrasts, with the highest frequencies in the DMN (50%), sensorimotor (33%), and executive prefrontal regions (33%). By contrast, control-higher contrasts were less frequent (10%, 95% CI 0.03–0.27), highlighting CIPN-related increases particularly in self-referential and somatosensory networks. Conclusions: Across analytic approaches, CIPN is characterized by reproducible alterations in the DMN and executive prefrontal and sensorimotor networks. These central pain signatures represent promising MRI-based biomarkers for identifying and monitoring CIPN in oncology. Full article

Peripheral nerve ischemia–reperfusion injury is considered to contribute to sensory disturbances that impair quality of life in patients with diabetic neuropathy and chemotherapy-induced neuropathy. However, the spinal mechanisms underlying these disturbances remain unclear, partly due to the lack of established animal models and evaluation systems. In the present study, we used a rat hindlimb ischemia–reperfusion model and in vivo extracellular recording to examine bidirectional changes in neuronal activity in the spinal dorsal horn. Ischemia was induced by tightly binding the rat ankle with a rubber band, followed by reperfusion. Behavioral analysis showed a significant increase in hindlimb licking behavior after reperfusion, indicating the development of sensory disturbance-like responses. Extracellular recordings from superficial dorsal horn neurons showed diverse patterns of spontaneous firing and responses to mechanical stimulation, with both hypersensitive and desensitized responses. Furthermore, mRNA expression levels of immediate early genes (Egr1, Egr3, and Fos) were upregulated in the spinal cord after reperfusion. These results suggest that this ischemia–reperfusion model reproduces complex neuronal responses relevant to peripheral neuropathy and provides a useful evaluation system for evaluating both increased and decreased neural activity. This approach may contribute to elucidating the mechanisms of sensory disturbances and to the development of new treatments for neuropathic conditions. Full article

As stem cell therapy in regenerative medicine becomes more socially accepted, human perinatal tissue is attracting attention as a source because it can be harvested non-invasively. Human placental extracts (HPEs), which are prepared using acid hydrolysis and autoclaving, have been approved for treating menopausal disorders and liver dysfunction. This study investigated a new HPE formulation prepared under milder conditions by omitting acid hydrolysis and autoclaving to improve its effectiveness. The new HPE contains relatively high-molecular-weight proteins, including high levels of thioredoxin-1, as well as primarily extracellular matrix proteins such as thrombospondin-1. These proteins appear to be intact or partially fragmented, but they can still potentially maintain their domain structure. The HPE showed both antioxidant and neurite outgrowth activities in a neuronal cell line SH-SY5Y. In a mouse model of hair graying caused by X-ray irradiation, multiple administration of the HPE significantly reduced it. Additionally, the HPE, but not heat-inactivated HPE, alleviated the mechanical allodynia in a mouse model with chemotherapy-induced peripheral neuropathy. Due to the fact that HPE can be produced non-invasively in large quantities in a short time without the need for culturing, the new HPE may have the potential to be an effective and feasible therapy via multiple mechanisms. Full article

Background/Objectives. Decades of research have failed to uncover effective approaches to prevent chemotherapy-induced peripheral neuropathy (CIPN), a common side effect of neurotoxic chemotherapy. Increased interest in placebo response as a potentially under-recognized confounder in CIPN trials was recently sparked by the results of a multisite NCI-funded phase II-III CIPN prevention study of duloxetine, a promising serotonin–norepinephrine reuptake inhibitor that enhances pain-inhibitory mechanisms within the central nervous system. Study findings revealed high and nearly equivalent response rates in three randomized treatment groups—little to no CIPN was reported by 65.2%, 66.0%, and 68.0% of study participants who received duloxetine 30 mg, 60 mg, or placebo treatment, respectively. Methods. We performed a meta-analysis of placebo response rates from seven randomized, double-blinded, placebo-controlled trials conducted over the past 20 years and comprising 191 placebo participants that were specifically testing interventions for oxaliplatin- and paclitaxel-induced peripheral neuropathy and that serially collected patient responses on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Chemotherapy-Induced Neuropathy questionnaire. Additionally, we sought to identify trial- and patient-specific factors that predicted higher placebo response rates from a participant-level pooled analysis. Results. The placebo response rate was 10.0% [95% CI: 5.8%, 16.6%] when response was defined more conservatively as patients reporting no neuropathy at all. When the placebo response was defined more broadly based on patients reporting no or a little neuropathy, the placebo response rate was higher (39.6% [95% CI: 27.4%, 53.2%]). Male participants, receipt of oxaliplatin, and a 2:1 randomization ratio favoring the intervention arm were individually associated with a higher placebo response. Conclusions. High placebo response rates can threaten scientific progress toward identifying effective treatments for cancer treatment-associated side effects, like CIPN. Careful attention to study design factors, participant eligibility, and patient and research staff expectations may help to minimize placebo response rates in future CIPN intervention studies. Full article

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of neurotoxic chemotherapy that can affect functioning and quality of life. Currently, duloxetine is the only recommended agent to treat painful CIPN; however, no effective pharmacological treatments have been approved for the prevention or cure of CIPN, highlighting the need to understand non-pharmacological strategies such as exercise. Given significant heterogeneity in the CIPN outcome measures chosen across studies, this scoping review aimed to identify the outcome measures used to evaluate the effectiveness of exercise interventions as a potential countermeasure for CIPN. Following the Arksey and O’Malley framework refined by Levac and colleagues, and the PRISMA-ScR guidelines, four databases were searched, and 20 studies were included in the review. Data were abstracted on study characteristics, cancer and chemotherapy factors, exercise prescription, outcome measures, and CIPN-related findings. Outcome measures varied widely across studies, encompassing various patient-reported, clinical, and functional measures. The most common patient-reported, clinical, and functional measures were the EORTC QLQ-CIPN20, vibration sensation, and maximal isometric strength, respectively. No study satisfied the components of the core outcome measure set proposed by Park and colleagues, limiting cross-study comparisons. These findings underscore the need for standardized CIPN outcome measures in future exercise studies to strengthen evidence synthesis and inform clinical practice. Full article

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity affecting 30–40% of patients treated with neurotoxic chemotherapy. Sensory symptoms arise from injury to dorsal root ganglion (DRG) neurons and their axons; yet, the underlying mechanisms remain incompletely understood. While human induced pluripotent stem cell (iPSC)-derived sensory neuron (iSN) monolayers have provided mechanistic insight, they lack the three-dimensional architecture and cellular heterogeneity of native DRG tissue. Here, we generated human iPSC-derived DRG organoids (iDRGOs) containing mixed neuronal and peripheral glial populations and established a quantitative neurite outgrowth assay to model chemotherapy-induced neurotoxicity in a 3D context. iDRGOs from three healthy donors were exposed to bortezomib, vincristine, or paclitaxel. All three drugs caused dose-dependent neurite outgrowth impairment without significant short-term changes in organoid size, consistent with early axonal injury. Vincristine reduced MAP2 levels when normalized to total protein, whereas bortezomib and paclitaxel showed divergent microtubule-associated responses compared to monolayer cultures. The developmental stage significantly influenced the baseline neurite outgrowth, highlighting the need for age standardization. These results establish iDRGOs as a physiologically relevant human platform that complements monolayer models for mechanistic studies and therapeutic screening in CIPN. Full article

Botulinum neurotoxin injections are used off-label to treat chronic pain, but their efficacy is limited and paralytic effects restrict clinical utility in these applications. Here, we investigated whether combining the light chain and translocation domains of botulinum neurotoxin A (BoNT/A) with the GM1-binding B subunit of cholera toxin would be beneficial in silencing pain-associated sensory neurons. Chimeric ChoBot was assembled via a coiled-coil linking technology and was shown to retain the enzymatic activity of BoNT/A in vitro and in vivo. In cultured dorsal root ganglion neurons, ChoBot cleaved SNAP25 in a calcitonin gene-related peptide (CGRP)-rich subpopulation of sensory neurons, resulting in marked inhibition of CGRP release. ChoBot had a lesser effect on the compound muscle action potentials of the rat gastrocnemius muscle than BoNT/A following subcutaneous injections. In rat models of pain, including chemotherapy-induced peripheral neuropathy, intraplantar administration of ChoBot significantly attenuated mechanical allodynia. Immunohistochemical analysis confirmed SNAP25 cleavage in NF200- and CGRP-expressing sensory fibres in the epidermis following a single injection. ChoBot also mediated SNAP25 cleavage in human neuroblastoma cells in culture. Together, these findings indicate that ChoBot enables a silencing of pain-associated sensory pathways, providing a new strategy for the development of new long-lasting analgesics for chronic pain. Full article

Background/Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a painful, debilitating condition that significantly impairs patient quality of life and often necessitates dose modification or discontinuation of chemotherapy, which can adversely impact patient outcomes and overall survival. This study aims to explore the experiences of cancer patients affected by CIPN and identify the challenges encountered in managing this condition. Methods: Data were collected through qualitative semi-structured interviews with 20 cancer patients with confirmed CIPN. The semi-structured interviews were held between April and June 2025 at a cancer center in the Qassim Region, Saudi Arabia, and were audio-recorded, transcribed, and analyzed using thematic analysis following Braun and Clarke. Results: Patients reported experiencing a considerable burden of CIPN symptoms, particularly during the early phases of chemotherapy, with some reporting gradual changes over time. Symptom unpredictability was reported across different types of cancer and regimens, regardless of age or gender. Sensory disruptions and functional impairments were prominent among many participants. Patients with higher levels of education, including those with family members in healthcare, demonstrated a stronger understanding of their condition and treatment explanations. Across cancer groups, patients expressed dissatisfaction with the prescribed therapies’ side effects. A subset of patients expressed a strong willingness to participate in clinical trials. Conclusions: The findings highlight the need for improved patient education, early symptom recognition, and comprehensive supportive care strategies. Healthcare providers should proactively address CIPN in treatment discussions and offer tailored interventions that go beyond physical symptoms. Additionally, further research is needed to identify and prevent CIPN across diverse populations. Full article

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity affecting many patients treated with neurotoxic agents, leading to persistent pain and impaired quality of life. Methods: In our trial, Trial ID: NCT06091553, 160 patients met the eligibility criteria and were randomized into three groups. First, Arm D (duloxetine). Second, Arm (D + A): duloxetine is augmented with amitriptyline. Third, Arm (D + G): duloxetine is augmented with gabapentin. The primary outcome is the difference in Pain Inventory—Short Form (BPI-SF) measured during the final follow-up week (Week 4 and Week 8) between the treatments. Results: All groups showed significant within-group reductions in pain scores from baseline to Weeks 4 and 8. Meanwhile, all groups exhibited numerical improvements for the average pain by Week 8. No statistically significant differences were found between groups at either Week 4 (p = 0.161) or Week 8 (p = 0.868). Similarly, the proportion of responders was comparable across treatment arms at both time points, with 74.5–82.8% achieving a clinically meaningful reduction in pain by Week 8 (p = 0.566). Conclusions: These findings support duloxetine as an evidence-based first-line therapy for painful CIPN, while combination regimens may be reserved for individualized use in patients with inadequate response, pending confirmation in larger multicenter trials. Full article

Chemotherapy-induced peripheral (CIPN) neuropathy is a common dose-limiting side effect affecting roughly 30–40% patients. Dorsal root ganglia (DRG) neurons are one of the main targets of CIPN as chemotherapy drugs may accumulate in DRG neurons. Chemotherapy drugs may induce direct damages on DRG neurons while also activating immune pathways, which results in the releasing of pro-inflammatory cytokines. This cascade may also damage neurons and amplify pain signaling. Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine with prominent immunomodulatory roles. Here, we report that TGF-β1 can promote axonal regeneration on DRG neurons injured by cisplatin via a suppressor of mothers against decapentaplegic (Smad) signaling pathway. To confirm the involvement of canonical TGF-β signaling, we applied the selective TGF-β type I receptor antagonist SB-431542 and performed a gene knockdown of Smad3 and Smad4, assessing their impacts on TGF-β1’s effects. Our results demonstrate that TGF-β1 could significantly enhance axonal regeneration in DRG, largely through a Smad4-dependent pathway, and we propose TGF-β1/Smad4 as a promising molecular target for treating CIPN. Full article

Background/Objectives: Many breast cancer patients treated with taxanes experience chemotherapy-induced peripheral neuropathy (CIPN). The early detection of CIPN may be facilitated by scoring systems. The existing Utah Early Neuropathy Scale (UENS) requires the presence of medical staff members. A self-assessment tool usable by patients is desired. Such an instrument was recently developed but had not yet been evaluated for the detection of CIPN. This prospective study aimed to identify the optimal cut-off score for the identification of moderate-to-severe CIPN in breast cancer survivors. Methods: Twenty-six breast cancer survivors (patients) who previously received taxane-based chemotherapy were included. Eighteen patients presenting with moderate-to-severe CIPN and eight patients without CIPN used the new scoring system (0–44 points). For each cut-off score, sensitivity, specificity, Youden index, and positive (PPV) and negative (NPV) predictive values were calculated. Patients rated their satisfaction with the tool. Dissatisfaction rates of >20% and >40%, respectively, would mean that it needed optimization or could not be used. Afterwards, the UENS (0–42 points) was applied by medical staff members. Results: For the new tool, a cut-off score of 9 points was found to be optimal for identifying moderate-to-severe CIPN. The sensitivity, specificity, Youden index, and PPV and NPV were 100% in each case. The dissatisfaction rate was 7.7%. When applying the UENS, the sensitivity, specificity, Youden index, and PPV and NPV were each 100% for a cut-off score of 6 points. Conclusions: The new self-assessment scoring system was highly accurate regarding the identification of moderate-to-severe CIPN. Patient satisfaction was high. When considering the limitations of this trial, the new instrument may be used in future studies. Full article

Background/Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of taxanes and platinum-based agents, impairing quality of life. Duloxetine is the only drug with proven efficacy, but is often limited by tolerability. AT-04 is a portable alternating magnetic field device that activates descending pain modulatory systems and has shown safety in other pain settings. This investigator-initiated trial evaluated the efficacy and safety of AT-04 for persistent CIPN. Methods: We conducted a randomized, double-blind, sham-controlled, multicenter phase II study. Patients with CIPN lasting ≥12 weeks after chemotherapy and pain NRS ≥ 4 were enrolled. Participants used AT-04 or sham devices twice daily for 12 weeks. The primary endpoint was the change in pain NRS on day 85. Secondary endpoints included tingling NRS, numbness NRS, CIPN20 subscales, and safety. Results: Twenty-eight patients were randomized (14 per arm). No significant difference was observed in pain NRS on day 85 {AT-04: −1.74 ± 0.6 vs. sham device: −1.45 ± 0.6; one-sided p = 0.36, effect size (ES) = 0.48}. CIPN20 motor scores improved with AT-04 on days 29 (−9.82 ± 13.8 vs. 0.74 ± 8.7, respectively; p = 0.035, ES = 0.92) and 57 (−11.81 ± 10.6 vs. −0.54 ± 6.7, respectively; p < 0.01, ES = 1.26). Among patients whose last chemotherapy had ended >1 year earlier (n = 16), motor scores improved from days 29 (−12.43 ± 10.3 vs. 2.38 ± 8.9, respectively; p < 0.01, ES = 1.55) to 85 (−11.76 ± 10.1 vs. −0.07 ± 11.5, respectively; p = 0.049, ES = 1.08), while sensory/autonomic scales showed trends. No treatment-related adverse events occurred in the AT-04 group. Conclusions: AT-04 did not significantly reduce pain NRS but improved motor function in CIPN patients, especially in those >1 year after chemotherapy. AT-04 may be a promising non-pharmacological option; larger confirmatory trials are required. Full article

Oxaliplatin-triggered chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cancer treatment that limits the efficacy of chemotherapy and negatively impacts patients’ quality of life dramatically. To better understand the mechanisms of CIPN and to screen for potential therapeutic targets, it is critical to have reliable in vitro assays that effectively mirror the neuropathy in vivo. In this study, we established a dorsal root ganglia (DRG) explant model. This model displayed dose-dependent inhibition of neurite outgrowth in response to oxaliplatin, while oxalic acid exhibited no significant impact on the regrowth of DRG. The robustness of this assay was further demonstrated by the inhibition of OCT2 transporter, which facilitates oxaliplatin accumulation in neurons, largely restoring the neurite regrowth capacity. Using this model, we revealed that oxaliplatin triggered a substantial increase of oxidative stress in DRG. Notably, inhibition of TXNIP with verapamil reduced oxidative stress levels. Our results demonstrated the use of DRG explants as an efficient model to study the mechanisms of CIPN and screen for potential treatments. Full article