Search Results (52)

Background/Objectives: Chemotherapy-induced neuropathic pain (CINP) represents a critical challenge in oncology, emerging as a common and debilitating side effect of widely used chemotherapeutic agents, such as paclitaxel (PTX). Current therapeutic interventions and preventive strategies for CINP are largely insufficient, as they fail to address the underlying peripheral nerve damage, highlighting an urgent need for the development of new drugs. This study aimed to investigate the dual-function effects on normal cell protection and tumor suppression of BMX-001, a redox-active manganese metalloporphyrin that has demonstrated antioxidant and anti-inflammatory properties, which offers potential in protecting central nervous system tissues and treating CINP. Methods: This study assessed BMX-001’s different roles in protecting normal cells while acting as a pro-oxidant and pro-inflammatory molecule in cancer cells in vitro. We also evaluated its neuroprotective effect in preclinical PTX-induced CINP models in vivo. Results: Our results showed significant reductions in mechanical and cold allodynia, decreased pro-inflammatory cytokine levels, and restored antioxidant capacity in peripheral nerves and dorsal root ganglia (DRGs) following BMX-001 treatment. Conclusions: Overall, our study highlights the therapeutic potential of BMX-001 to mitigate CINP and enhance anticancer efficiency. Its dual-selective mechanism supports the future clinical investigation of BMX-001 as a novel adjunct to chemotherapeutic regimens. Full article

Background and Clinical Significance: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and limiting complication of oncological treatment, particularly in patients receiving oxaliplatin. Its onset can significantly affect the quality of life and compromise the continuity of the antineoplastic therapy. Due to the limited efficacy of available pharmacological therapies, percutaneous electrical nerve stimulation (PENS) has been proposed as a non-invasive alternative for symptom management. Case presentation: We report the case of a 75-year-old woman with colorectal adenocarcinoma who developed CIPN following oxaliplatin administration. She underwent a 12-week course of PENS targeting the median nerve, with weekly sessions conducted without interruption of chemotherapy and without adverse effects. The patient showed progressive improvement in neurosensory symptoms, as measured by the EORTC QLQ-CIPN20 questionnaire. Quantitative sensory testing revealed normalization of thermal and vibratory sensitivity and improved mechanical detection thresholds. The cumulative oxaliplatin dose was maintained throughout treatment. Conclusions: PENS may offer an effective and safe therapeutic option for managing CIPN, enabling symptom control without compromising oncological treatment. This case supports the need for controlled clinical trials to confirm efficacy and establish standardized protocols. Full article

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy. CIPN can lead to a dose reduction and/or the interruption of chemotherapy, limiting its effectiveness, while chronic CIPN decreases patients’ quality of life. Improvements in cancer treatment and patients’ survival have increased the number of patients living with CIPN. The only evidence-based treatment for CIPN-related pain, duloxetine, provides only modest clinical benefit, and there is no effective clinical management option for numbness and tingling. Several experimental studies and clinical reports suggest that adjuvant ozone treatment may be beneficial in managing CIPN. Methods: This narrative review aims to provide an overview of current knowledge regarding CIPN and ozone therapy. Specifically, it summarizes experimental studies (18) and clinical reports (27) published between 1995 and 2025 that offer preliminary evidence supporting the potential role of ozone treatment in managing CIPN, highlighting the need for ongoing randomized clinical trials to establish its efficacy. Additionally, this review highlights existing gaps in the literature and proposes directions for future research. Results: The hypothesized mechanisms of action and experimental findings suggest that ozone therapy may be a valuable intervention for CIPN, a concept supported by preliminary clinical observations. Conclusions: Clinically relevant approaches for established CIPN are currently unavailable. While preliminary data suggest a potential role of ozone therapy, clinical evidence remains limited. Further high-quality randomized controlled trials are needed to confirm its efficacy and safety in this context; several trials are currently ongoing. Full article

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating side effect of cancer treatment. Characterized by symptoms like pain, numbness, and muscle weakness, CIPN significantly impacts patients’ quality of life. Current management strategies vary, with limited consensus on effective treatments. This scoping review aims to explore comprehensive rehabilitation interventions for CIPN, focusing on enhancing patient well-being and functional abilities. Methods: A scoping review, guided by Arksey and O’Malley’s framework and Levac et al.’s refinements, was conducted to assess rehabilitation programs for CIPN. Searches across six databases were performed, with inclusion and exclusion criteria focusing on studies with physical rehabilitation interventions. Data were charted, detailing interventions, demographics, and outcomes. Results were synthesized descriptively and presented narratively with tables. Results: The review included 24 studies covering diverse cancer types and treatments, involving a total of 1167 participants. Various interventions for CIPN were assessed, and results were thematically categorized according to exercise category. Physical modalities like ultrasound and exercise showed promise in symptom relief for colorectal and breast cancer patients. No distinct advantage was found in the timing of exercise interventions. Complementary therapies such as acupuncture and yoga demonstrated effectiveness in managing CIPN symptoms. Conclusions: This review highlights the effectiveness of diverse physical and complementary interventions in managing CIPN, advocating for their integration into standard protocols. It emphasizes the need for holistic, patient-centered approaches that combine exercises, physical therapy, and complementary therapies to improve patient outcomes. These findings set a direction for future research and clinical practices focused on comprehensive and personalized CIPN management strategies. Full article

Background and Aim: Neuropathic pain leads to a significant deterioration in health-related quality of life (HRQOL). Treating neuromusculoskeletal pain is especially important to prevent and improve physical frailty and the locomotive syndrome. Varied pharmacotherapies could be applicable for neuropathic pain patients, but evidence has been limited for a wide range of neuropathic pain conditions with different etiologies. The aim of this review was to highlight mirogabalin, a novel calcium channel α2δ ligand which was first approved in Japan, and which is effective for various types of neuropathic pain diseases. Methods: We conducted a narrative review of the recent evidence that mirogabalin has significant analgesic potency for varied types of neuropathic pain conditions. Futher, this review highlighted specific advantages over other calcium channel ligands. Results: Analgesic potency of mirogabalin could cover peripheral neuropathic pain conditions including post-herpetic neuralgia, diabetic peripheral neuropathy, cauda equina syndrome caused by lumbar spinal stenosis, radiculopathy caused by cervical spondylosis, and also central neuropathic pain conditions like spinal cord injury. Mirogabalin consistently demonstrated daytime sleepiness and dizziness as adverse effects, but most of these were mild. Conclusions: Mirogabalin is recommended as the first-line drug against most molecular mechanisms that cause neuropathic pain regardless of whether they have a peripheral or central origin. Mirogabalin demonstrates relatively less daytime sleepiness, making it age-friendly in the current global situation where population aging is accelerated. Considering the epidemic of ‘opiophobia’ in Japan and other countries, pharmacotherapy using mirogabalin could treat neuropathic pain associated with cancer and its treatment (e.g., chemotherapy-induced peripheral neuropathy), as well as non-cancer etiologies worldwide. Full article

This study investigates the role of p38 mitogen-activated protein kinase (MAPK) activation in dorsal root ganglion (DRG) neurons in the development and progression of chemotherapy-induced peripheral neuropathy (CIPN). This research evaluates whether inhibiting activation of p38 MAPK could reduce neuropathic outcomes in a transgenic breast cancer mouse model (C3TAg) and wild-type mice (FVB/N) treated with cisplatin. Cisplatin treatment stimulated p38 MAPK phosphorylation and nuclear translocation in DRG neurons. Neflamapimod, a specific inhibitor of p38 MAPK alpha (p38α), proven to be safe in clinical trials, inhibited neuronal cisplatin-induced p38 MAPK phosphorylation in vitro and in vivo. Neflamapimod also reduced cisplatin-induced oxidative stress, mitochondrial dysfunction, and cleaved caspase-3 expression in DRG neurons in vitro, protecting neuronal integrity and preventing axonal damage. Functionally, neflamapimod improved mechanical and musculoskeletal hyperalgesia, and cold sensitivity in cisplatin-treated mice, reversing neuropathic pain and neurotoxicity. This study identifies p38 MAPK activation as a critical driver of CIPN and highlights its potential as a therapeutic target for CIPN. Targeting p38 MAPK activation with neflamapimod offers a promising strategy to mitigate neurotoxicity and hyperalgesia without exacerbating cancer progression, positioning it as a novel intervention for CIPN. Full article

Background: Chemotherapy-induced peripheral neuropathy (CIPN) affects 20–85% of individuals exposed to neurotoxic chemotherapeutic agents. Perineural electrical dry needling (PEDN) and neural mobilization (NM) interventions may be beneficial in the management of chronic neurogenic pain; however, there is a paucity of research on the efficacy of both interventions for CIPN. Methods: Three patients were referred to an outpatient physical therapy clinic with chronic neuropathic pain associated with CIPN. Each underwent PEDN and NM twice weekly until goals were met or progress stalled. The primary outcome measure was the Numeric Pain Rating Scale (NPRS). Secondary outcomes included the Global Rating of Change (GROC) and the Lower Extremity Functional Scale (LEFS). All outcome measures were assessed at evaluation and discharge. Results: At discharge, patients A and B exceeded the minimum clinically important difference (MCID) for the primary and secondary outcome measures, indicating decreased neuropathic pain and improved lower extremity function. Patient C improved in all outcome measures but only experienced clinically meaningful changes in the NPRS and LEFS, not the GROC. Conclusions: Following 4–8 sessions of PEDN and NM, three patients with CIPN demonstrated clinically meaningful improvements in chronic lower extremity neuropathic pain and function. PEDN and NM may be beneficial in the management of patients presenting with chronic neuropathic pain secondary to CIPN. Full article

Neuropathic pain (NP) is a common complication associated with some types of childhood cancer, mainly due to nerve compression, chronic post-surgical pain, chemotherapy, and radiotherapy. NP is usually less responsive to traditional analgesics, and there is generally a lack of evidence on its management in cancer patients, leading to recommendations often based on clinical trials conducted on other forms of non-malignant NP. In pediatric oncology, managing NP is still very challenging for physicians. Different factors contribute to increasing the risk of undertreatment: (a) children may be unable to describe the quality of pain; therefore, the risk for NP to be underestimated or remain unrecognized; (b) specific tools to diagnose NP have not been validated in children; (c) there is a lack of randomized clinical trials involving children, with most evidence being based on case series and case reports; (d) most drugs used for adult patients are not approved for childhood cancers, and drug regulation varies among different countries; (e) recommendations for pediatric pain treatment are still not available. In this paper, a multidisciplinary team will review the current literature regarding children with cancer-related NP to define the best possible diagnostic strategies (e.g., clinical and instrumental tests) and propose a therapeutic care pathway, including both non-pharmacological and pharmacological approaches, which could help pediatricians, oncologists, neurologists, and pain therapists in designing the most effective multidisciplinary approach. Full article

Chemotherapy-induced peripheral neuropathy and the accompanying affective disorders are serious side effects, and their resolution is not guaranteed. Oxidative stress and elevated levels of Nod-like receptor protein 3 (NLRP3) have been detected in the peripheral and central nervous systems of animals with neuropathic pain provoked by several antineoplastic drugs, such as paclitaxel (PTX). Several studies have further indicated that NLRP3 inflammasome inhibition could be an approach for treating chronic pain, but its impact on the anxiodepressive-like behaviors and memory deficits related to PTX-provoked neuropathy has not yet been investigated. MCC950 is a potent and specific inhibitor of the NLRP3 pathway that acts through inhibiting NLRP3 activation and inflammasome formation. We hypothesized that the administration of MCC950 could alleviate the affective and cognitive disorders accompanying PTX-provoked neuropathy. Using male C57BL/6 mice, we assessed the effects of MCC950 on the mechanical and thermal allodynia, anxiodepressive-like behavior, and memory deficits incited by this taxane. The results indicated that the intraperitoneal administration of 10 mg/kg of MCC950 twice daily for three consecutive days fully reversed the PTX-induced mechanical and thermal allodynia. This treatment also completely attenuated the anxiolytic (p < 0.004) and depressive-like behaviors (p < 0.022) and memory deficits (novel object recognition test; p < 0.0018) incited by PTX. These actions were mainly achieved through blocking NLRP3 inflammasome activation in the sciatic nerve, amygdala, and hippocampus, and oxidative stress in the amygdala and hippocampus. MCC950 also normalized the p-ERK 1/2 overexpression in the sciatic nerve and apoptotic responses in the sciatic nerve and the amygdala. This study suggests that MCC950 might be a promising treatment for PTX-induced mental illnesses and neuropathy. Full article

Objectives: The aim of this study was to evaluate the effects of spinal cord stimulation (SCS) on pain, neuropathic symptoms, and other health-related metrics in patients with chronic painful peripheral neuropathy (PN) from multiple etiologies. Methods: A prospective single center observational longitudinal cohort study assessed SCS efficacy from April 2023 to May 2024, with follow-ups at 2, 4, 6, and 12 months in 19 patients suffering from the painful polyneuropathy of diverse etiologies: diabetic (DPN), idiopathic (CIAP), chemotherapy-induced (CIPN), and others. Patients were implanted with a neurostimulator (WaveWriter Alpha^TM, Boston Scientific Corporation, Valencia, CA, USA) and percutaneous leads targeting the lower limbs (T10–T11) and, if necessary, the upper limbs (C4–C7). Stimulation programming was individualized based on patient preference and best response. Assessments were performed before and after implantation and included pain intensity (VAS and DN4), neuropathic pain symptoms (NPSI and SF-MPQ-2), autonomic symptoms (SFN-SIQ and SAS), sensory and small fiber nerve injury (UENS), functionality (GAF), sleep (CPSI), global impression of change (CGI and PGI), and quality of life (EQ-VAS and EQ-5D). Intra-epidermal nerve fiber density (IENFD) via skin biopsy was also performed at baseline (diagnostic) and after 12 months to assess potential small fiber re-growth. Statistical analyses were conducted to determine the evolution of treatment success. Results: To date, 19 patients have undergone implantation and completed follow-up. SCS produced a significant consistent and sustained improvement in pain intensity by 49% in DN4 and 76% in VAS, in neuropathic pain symptoms by 73%, in autonomic symptoms by 26–30%, in the sensorimotor physical exam by 8%, in functionality by 44%, in sleep by 74%, and in quality of life (69% for EQ-VAS and 134% EQ-5D). Both clinicians and patients had a meaningful global impression of change, at 1.1 and 1.3, respectively. Distal intra-epidermal nerve fiber density improved by 22% at 12 months while proximal intra-epidermal nerve fiber density decreased by 18%. Conclusions: SCS is an effective therapy for managing various types of PN. Full article

Vincristine, a vinca alkaloid, is used in chemotherapy protocols for cancers such as acute leukemia, Hodgkin’s disease, neuroblastoma, cervical carcinoma, lymphomas, breast cancer, and melanoma. Among the common adverse effects of vincristine is peripheral neuropathy, with most patients receiving a cumulative dose over 4 mg/m² who develop varying degrees of sensory neuropathy. The onset of vincristine-induced peripheral neuropathy can greatly affect patients’ quality of life, often requiring dose adjustments or the discontinuation of treatment. Moreover, managing vincristine-induced peripheral neuropathy is challenging, with few effective therapeutic strategies available. In the past decade, preclinical studies have explored diverse substances aimed at preventing or alleviating VIPN. Our review consolidates these findings, focusing on the analgesic efficacy and potential mechanisms of various agents, including pharmaceutical drugs, natural compounds, and antioxidants, that show promise in reducing neuropathic pain and protecting neural integrity in preclinical models. Key novel therapeutic options, such as metabolic agents (liraglutide), enzyme inhibitors (ulinastatin), antipsychotics (aripiprazole), interleukin-1 receptor antagonists (anakinra), hormones (oxytocin), and antioxidants (thioctic acid), are highlighted for their neuroprotective, anti-inflammatory, and antioxidant effects. Through this synthesis, we aim to enhance the current understanding of VIPN management by identifying pharmacological strategies that target critical molecular pathways, laying the groundwork for future clinical studies. By clarifying these novel pharmacological approaches and elucidating their mechanisms of action, this review provides a foundation for developing more effective VIPN treatment strategies to ultimately improve patient outcomes. Full article

Cancer, one of the leading causes of death worldwide, is on the rise. The high toxicity of conventional chemotherapy, often applied as drug cocktails, and the development of resistance limit the use of antineoplastic drugs and reduce the quality of life. With easier access, a growing number of patients are using cannabis (cannabinoids) for alleviation of their symptoms, and in the hope of improving survival. This article summarizes results observed with combinations of phytocannabinoids and standard chemotherapeutic agents in animal tumour models and in patients. It is limited to approved phytocannabinoids. Preliminary preclinical data suggest that conventional antineoplastic agents combined with cannabinoids exert enhanced anti-cancer effects, reduce resistance development and improve survival. Corresponding experiences with patients are still very limited and only concern a few patients with glioblastoma and pancreatic cancer. Benefits of combinations containing cannabinoids have also been reported for chemotherapy-induced nausea and vomiting, loss of appetite (dronabinol), and chemotherapy-induced peripheral neuropathic pain and anxiety (cannabidiol). In addition, phytocannabinoids, particularly cannabidiol, may play a role in protecting organs such as the heart, lungs or kidneys from chemotherapy-related toxicity. Although the results are promising, more research is needed to ensure whether the benefits of adjuvant cannabinoids outweigh the potential risks. Full article

Chemotherapy-provoked peripheral neuropathy and its associated affective disorders are important adverse effects in cancer patients, and its treatment is not completely resolved. A recent study reveals a positive interaction between molecular hydrogen (H₂) and a heme oxygenase (HO-1) enzyme inducer, cobalt protoporphyrin IX (CoPP), in the inhibition of neuropathic pain provoked by nerve injury. Nevertheless, the efficacy of CoPP co-administered with hydrogen-rich water (HRW) on the allodynia and emotional disorders related to paclitaxel (PTX) administration has not yet been assessed. Using male C57BL/6 mice injected with PTX, we examined the effects of the co-administration of low doses of CoPP and HRW on mechanical and thermal allodynia and anxiodepressive-like behaviors triggered by PTX. Moreover, the impact of this combined treatment on the oxidative stress and inflammation caused by PTX in the amygdala (AMG) and dorsal root ganglia (DRG) were studied. Our results indicated that the antiallodynic actions of the co-administration of CoPP plus HRW are more rapid and higher than those given by each of them when independently administered. This combination inhibited anxiodepressive-like behaviors, the up-regulation of the inflammasome NLRP3 and 4-hydroxynonenal, as well as the high mRNA levels of some inflammatory mediators. This combination also increased the expression of NRF2, HO-1, superoxide dismutase 1, glutathione S-transferase mu 1, and/or the glutamate-cysteine ligase modifier subunit and decreased the protein levels of BACH1 in the DRG and/or AMG. Thus, it shows a positive interaction among HO-1 and H₂ systems in controlling PTX-induced neuropathy by modulating inflammation and activating the antioxidant system. This study recommends the co-administration of CoPP plus HRW as an effective treatment for PTX-provoked neuropathy and its linked emotive deficits. Full article

Chemotherapy-induced peripheral neuropathy (CIPN) remains a clinical challenge for up to 80% of breast cancer survivors. In an open-label study, participants underwent three interventions: standard care (duloxetine) for 1 month (Phase 1), oral cannabidiol (CBD) for 2 months (Phase 2), and CBD plus multi-modal exercise (MME) for another 2 months (Phase 3). Clinical outcomes and gut microbiota composition were assessed at baseline and after each phase. We present the case of a 52-year-old female with a history of triple-negative breast cancer in remission for over five years presenting with CIPN. She showed decreased monocyte counts, c-reactive protein, and systemic inflammatory index after each phase. Duloxetine provided moderate benefits and intolerable side effects (hyperhidrosis). She experienced the best improvement and least side effects with the combined (CBD plus MME) phase. Noteworthy were clinically meaningful improvements in CIPN symptoms, quality of life (QoL), and perceived physical function, as well as improvements in pain, mobility, hand/finger dexterity, and upper and lower body strength. CBD and MME altered gut microbiota, showing enrichment of genera that produce short-chain fatty acids. CBD and MME may improve CIPN symptoms, QoL, and physical function through anti-inflammatory and neuroprotective effects in cancer survivors suffering from long-standing CIPN. Full article

The peripheral nervous system can encounter alterations due to exposure to some of the most commonly used anticancer drugs (platinum drugs, taxanes, vinca alkaloids, proteasome inhibitors, thalidomide), the so-called chemotherapy-induced peripheral neurotoxicity (CIPN). CIPN can be long-lasting or even permanent, and it is detrimental for the quality of life of cancer survivors, being associated with persistent disturbances such as sensory loss and neuropathic pain at limb extremities due to a mostly sensory axonal polyneuropathy/neuronopathy. In the state of the art, there is no efficacious preventive/curative treatment for this condition. Among the reasons for this unmet clinical and scientific need, there is an uncomplete knowledge of the pathogenetic mechanisms. Ion channels and transporters are pivotal elements in both the central and peripheral nervous system, and there is a growing body of literature suggesting that they might play a role in CIPN development. In this review, we first describe the biophysical properties of these targets and then report existing data for the involvement of ion channels and transporters in CIPN, thus paving the way for new approaches/druggable targets to cure and/or prevent CIPN. Full article