Chemotherapy-induced Neuropathy Research Articles

Buprenorphine as a Treatment for Severe Chemotherapy-Induced Neuropathy – A Case Report

Buprenorphine as a Treatment for Severe Chemotherapy-Induced Neuropathy – A Case Report

Postural control characteristics of breast cancer (BC) survivors with chronic chemotherapy-induced neuropathy (CIN)

Postural control characteristics of breast cancer (BC) survivors with chronic chemotherapy-induced neuropathy (CIN)

Major clinical approaches of dental treatment in cancer patients: a systematic review

Introduction: According to the National Cancer Institute, a total of 16,290 new cases of oral cancer were estimated in Brazil in 2017, with 12,370 new cases of oral cavity cancer in men and 4,010 in women corresponding to an estimated risk of 11.54 cases new for every 100 thousand men and 3.92 for each 100 thousand women. In this sense, oral cancer therapy is associated with a multitude of head and neck sequelae including hyposalivation, increased risk of tooth decay, osteoradionecrosis of the jaw, radiation fibrosis syndrome, mucositis, chemotherapy-induced neuropathy, dysgeusia, dysphagia, mucosal lesions, trismus, and infections. Objective: It was to present the main clinical approaches to dental treatment in cancer patients through a systematic review. Methods: The PRISMA Platform systematic review rules were followed. The search was carried out from November 2023 to February 2024 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 156 articles were found, 58 articles were evaluated in full and 29 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 32 studies with a high risk of bias and 20 studies that did not meet GRADE and AMSTAR-2. Most studies did not show homogeneity in their results, with X2=61.8%>50%. It was concluded that preparing a comprehensive treatment plan for cancer patients is essential to help minimize the risks of developing these oral and dental complications. Additionally, dentists should consider the patient's ongoing oncology therapy for those patients who see the dentist while receiving cancer treatment.

EXPLORING THE POTENTIAL PHARMACOLOGICAL EFFECT OF THYMOQUINONE IN AMELIORATING THE ACQUISITION AND EXPRESSION OF VINCRISTINE INDUCED NEUROPATHIC PAIN IN MICE

Background: Chemotherapy-induced neuropathy (CIPN) is the most severe consequence, causing both sensory and motor impairment with an incidence of between 19% and over 85%. Leukaemia, lymphoma, and sarcoma are just a few of the cancers that are treated using vincristine (VCR), a typical anticancer treatment used in chemotherapy. Peripheral neuropathy caused by vincristine is the primary impediment to the efficacy of ongoing anti-cancer treatment and continued use. Objectives: The current study's goal was to contemplate the significance of thymoquinone on the development and expression of vincristine-induced neuropathy. Methodology: All groups except normal saline were administered vincristine 0.1mg/kg i.p for 14 days. In selected groups Gabapentin (75mg/kg) and thymoquinone were administered at 10, 20, and 30 mg/kg/day for 14 days orally along with vincristine (acquisition) and once at day 14 (expression). Thermal hyperalgesia and mechanical allodynia were quantified on days 1, 6, and 14 after 30, 60, 90, and 120 minutes. The data were processed using the Students’t-test and post hoc Dunnett's test. Results: The acquisition and expression of thermal hyperalgesia as well as mechanical allodynia was significantly improved by thymoquinone at all the tested doses at days 6 and 14 as well as after 30, 60, 90, and 120 minutes significant improvement was observed. Conclusion: It is manifested that TQ can be an impending candidate for the management of vincristine-induced neuropathy.

In Rats, the Chemotherapeutic Drug Vincristine-Induced Neuropathic Nociception is Suppressed When Cannabinoid CB1 and CB2 Receptors are Activated

Rats were used to test the potential of cannabis to reduce mechanical hypersensitivity, or mechanical allodynia, which was brought on by vincristine chemotherapy. After that, action sites were located. Method of experimentation: After ten daily injections of vincristine, mechanical hypersensitivity developed in comparison to those that received saline at the same periods. The effects on chemotherapy-induced neuropathy were assessed for the CB1/CB2 receptor agonist WIN55, 212-2, the receptor-inactive enantiomer WIN55, 212-3, the CB2-selective agonist (R,S)-AM1241, the opiate agonist morphine, and vehicle. To determine the locations of action, WIN55, 212-2 was injected either locally in the hind paw or intrathecally (i.t.). By employing competitive antagonists for either CB1 (SR141716) or CB2 receptors (SR144528), pharmacological selectivity was demonstrated. Vincristine-evoked mechanical allodynia was decreased when WIN55, 212-2, but not WIN55, 212-3, were administered systemically. A change in the dose-response curve to the left was noticed after WIN55, 212-2 in comparison to morphine therapy. Antibodies of CB1 (SR141716) and CB2 (SR144528) inhibited WIN55, 212-2’s anti-allodynic actions. Via a CB2 mechanism, (R,S)-AM1241 reduced c-induced mechanical hypersensitivity. Without causing catalepsy, both cannabinoid agonists reduced the mechanical hypersensitivity brought on by vincristine. Cannabis-induced neuropathy may be modulated by cannabinoids at spinal sites of action. When delivered intraperitoneally, WIN55, 212-2 but not WIN55,212-3 inhibited vincristine-evoked mechanical hypersensitivity at dosages that were inert after local hindpaw injection. Spinal co-administration of CB1 and CB2 antagonists inhibited WIN55,212-2’s anti-allodynic effects.By activating CB1 and CB2 receptors, cannabinoids inhibit the maintenance of vincristine-induced mechanical allodynia. The spinal cord is involved in the mediation of these anti-allodynic actions, at least partially.

Comparisons of telemedicine and in-person visits: Utilization, oncology services and satisfaction among patients with breast cancer.

517 Background: Since the COVID-19 pandemic, telemedicine utilization has expanded in oncology settings and helps facilitate access to oncology services for breast cancer patients (pts). However, it remains unclear what types of oncology services are received via telemedicine and whether receipts of these services differ between telemedicine and in-person visits. Methods: We conducted a cross-sectional study surveying breast cancer pts in the Chicago Multiethnic Epidemiologic Breast Cancer Cohort from July-September 2022. Telemedicine (i.e., audio call [AC], video conference [VC], and both) and in-person visits were measured as having had a telemedicine and in-person visit with a provider in the past 12 months. Types of oncology services included treatment consultation, management of side effects/symptoms, review of lab, screening or pathology results, cancer genetic counseling, and clinical trial follow-up. We assessed common side effects/symptoms discussed during telemedicine or in-person visits. Satisfaction was assessed using a 5-point Likert scale. McNemar’s test was used to evaluate paired data on types of oncology services between telemedicine and in-person visits. Results: Of 1,160 pts (mean age 61.8 years, SD 12.0), 72.8% were White, followed by 19.7% Black, 4.5% Asian, and 3.0% Hispanic; 70.8% were privately insured and 23.0% on Medicaid/Medicare; 81.0% had stage I-III disease. Overall, 36.0% used telemedicine (of these, 65.0% VC, 22.7% AC, and 12.2% both) and 92.4% had in-person visits. Telemedicine users reported 93.9% and 95.5% of somewhat-to-extreme satisfaction with AC and VC, respectively, and 61.8% were likely or very likely to continue using telemedicine. In pts having both telemedicine and in-person visits, we observed differences between these visits in management of side effects/symptoms (15 vs. 54, p<.001), review of lab, screening or pathology results (26 vs. 90, p<.001), or trial follow-up (4 vs. 12, p=.046). However, there were no differences in treatment consultation (45 vs. 55, p=.317) or cancer genetic counseling (11 vs. 19, p=.144). Furthermore, BC pts who had in-person visits reported higher percentages of discussion of fatigue (50.3% vs. 41.1%), hot flashes (45.6% vs. 33.9%), lymphedema (26.0% vs. 19.6%), chemotherapy-induced neuropathy (24.9% vs. 19.5%), or nausea/vomiting (16.0% vs. 8.9%) than those used telemedicine; whereas a higher proportion of pts having discussed depressive symptoms via telemedicine than in-person visits (37.5% vs. 29.6%). Conclusions: In this multiethnic cohort of breast cancer pts, telemedicine use was prevalent and achieved high-level satisfaction. Our findings also suggest that both telemedicine and in-person visits are equally likely to include treatment consultation and genetic counseling, and telemedicine may be in greater need among breast cancer pts with mental health challenges.

Exploring Cholinergic Compounds for Peripheral Neuropathic Pain Management: A Comprehensive Scoping Review of Rodent Model Studies.

Neuropathic pain affects about 7-8% of the population, and its management still poses challenges with unmet needs. Over the past decades, researchers have explored the cholinergic system (muscarinic and nicotinic acetylcholine receptors: mAChR and nAChR) and compounds targeting these receptors as potential analgesics for neuropathic pain management. This scoping review aims to provide an overview of studies on peripheral neuropathic pain (PNP) in rodent models, exploring compounds targeting cholinergic neurotransmission. The inclusion criteria were original articles on PNP in rodent models that explored the use of compounds directly targeting cholinergic neurotransmission and reported results of nociceptive behavioral assays. The literature search was performed in the PubMed and Web of Science databases (1 January 2000-22 April 2023). The selection process yielded 82 publications, encompassing 62 compounds. The most studied compounds were agonists of α4β2 nAChR and α7 nAChR, and antagonists of α9/α10 nAChR, along with those increasing acetylcholine and targeting mAChRs. Studies mainly reported antinociceptive effects in traumatic PNP models, and to a lesser extent, chemotherapy-induced neuropathy or diabetic models. These preclinical studies underscore the considerable potential of cholinergic compounds in the management of PNP, warranting the initiation of clinical trials.

Cisplatin-induced DNA crosslinks trigger neurotoxicity in C. elegans

The anticancer drug cisplatin (CisPt) injures post-mitotic neuronal cells, leading to neuropathy. Furthermore, CisPt triggers cell death in replicating cells. Here, we aim to unravel the relevance of different types of CisPt-induced DNA lesions for evoking neurotoxicity. To this end, we comparatively analyzed wild-type and loss of function mutants of C. elegans lacking key players of specific DNA repair pathways. Deficiency in ercc-1, which is essential for nucleotide excision repair (NER) and interstrand crosslink (ICL) repair, revealed the most pronounced enhancement in CisPt-induced neurotoxicity with respect to the functionality of post-mitotic chemosensory AWA neurons, without inducing neuronal cell death. Potentiation of CisPt-triggered neurotoxicity in ercc-1 mutants was accompanied by complex alterations in both basal and CisPt-stimulated mRNA expression of genes involved in the regulation of neurotransmission, including cat-4, tph-1, mod-1, glr-1, unc-30 and eat-18. Moreover, xpf-1, csb-1, csb-1;xpc-1 and msh-6 mutants were significantly more sensitive to CisPt-induced neurotoxicity than the wild-type, whereas xpc-1, msh-2, brc-1 and dog-1 mutants did not distinguish from the wild-type. The majority of DNA repair mutants also revealed increased basal germline apoptosis, which was analyzed for control. Yet, only xpc-1, xpc-1;csb-1 and dog-1 mutants showed elevated apoptosis in the germline following CisPt treatment. To conclude, we provide evidence that neurotoxicity, including sensory neurotoxicity, is triggered by CisPt-induced DNA intra- and interstrand crosslinks that are subject of repair by NER and ICL repair. We hypothesize that especially ERCC1/XPF, CSB and MSH6-related DNA repair protects from chemotherapy-induced neuropathy in the context of CisPt-based anticancer therapy.

Biomechanical effect of neurologic dance training (NDT) for breast cancer survivors with chemotherapy-induced neuropathy: study protocol for a randomized controlled trial and preliminary baseline data

BackgroundBreast cancer (BC) is among the most common forms of cancer experienced by women. Up to 80% of BC survivors treated with chemotherapy experience chemotherapy-induced neuropathy (CIN), which degrades motor control, sensory function, and quality of life. CIN symptoms include numbness, tingling, and/or burning sensations in the extremities; deficits in neuromotor control; and increased fall risk. Physical activity (PA) and music-based medicine (MBM) are promising avenues to address sensorimotor symptoms. Therefore, we propose that we can combine the effects of music- and PA-based medicine through neurologic dance training (NDT) through partnered Adapted Tango (NDT-Tango). We will assess the intervention effect of NDT-Tango v. home exercise (HEX) intervention on biomechanically-measured variables. We hypothesize that 8 weeks of NDT-Tango practice will improve the dynamics of posture and gait more than 8 weeks of HEX.MethodsIn a single-center, prospective, two-arm randomized controlled clinical trial, participants are randomly assigned (1:1 ratio) to the NDT-Tango experimental or the HEX active control intervention group. Primary endpoints are change from baseline to after intervention in posture and gait. Outcomes are collected at baseline, midpoint, post, 1-month follow-up, and 6-month follow-up. Secondary and tertiary outcomes include clinical and biomechanical tests of function and questionnaires used to compliment primary outcome measures. Linear mixed models will be used to model changes in postural, biomechanical, and PROs. The primary estimand will be the contrast representing the difference in mean change in outcome measure from baseline to week 8 between treatment groups.DiscussionThe scientific premise of this study is that NDT-Tango stands to achieve more gains than PA practice alone through combining PA with MBM and social engagement. Our findings may lead to a safe non-pharmacologic intervention that improves CIN-related deficits.Trial registrationThis trial was first posted on 11/09/21 at ClinicalTrials.gov under the identifier NCT05114005.

An In-Vivo Study to Evaluate the Efficacy of Padmaka (Prunus Cerasoides) as a Vedanasthapak in Supti (Numbness) Caused by Neuropathy in Wistar Rats

This research article attempts to address the main symptom of chemotherapy-induced neuropathy, which is ‘numbness’. Neuropathic pain is a common side effect of anticancer drugs that significantly reduces a patient's quality of life. This work redefines the term "Vedanasthapan" by explaining the act of regaining sensation along with its analgesic properties. This study was carried out by using an animal model of rats prepared by using an anti-cancer agent cisplatin. Before inducing cisplatin, normal latency periods of all rats were noted by ‘Hot plate’ method. Cisplatin was given to the rats to induce numbness with the interval of a week for two weeks. Four groups of rats having six rats in each group were labelled as – ‘control group’ treated with daily diet only, ‘vehicle group’ treated with carboxymethyl cellulose, ‘positive control’ treated with pregabalin, and ‘test drug group’ treated with ‘Padmaka’. After the treatment period, all groups were tested on a hot plate to record the latency time of rats. All obtained data were processed by ANOVA test and Tukey-Kramer multiple comparison test. It showed that the means of all groups differed significantly from each other. The mean time of the positive control group was 9.06 seconds and that of the experimental drug group was 12.9 seconds, which is close to the mean time in the normal state (7.36 seconds). While the control group and the vehicle group were far apart. This means that the experimental drug Padmaka is also useful in reversing cisplatin-induced numbness. Further clinical studies are needed to fully understand its range of action.

Broad-spectrum neuroprotection exerted by DDD-028 in a mouse model of chemotherapy-induced neuropathy.

Neurotoxicity of chemotherapeutics involves peculiar alterations in the structure and function, including abnormal nerve signal transmission, of both the peripheral and central nervous system. The lack of effective pharmacological approaches to prevent chemotherapy-induced neurotoxicity necessitates the identification of innovative therapies. Recent evidence suggests that repeated treatment with the pentacyclic pyridoindole derivative DDD-028 can exert both pain-relieving and glial modulatory effects in mice with paclitaxel-induced neuropathy. This work is aimed at assessing whether DDD-028 is a disease-modifying agent by protecting the peripheral nervous tissues from chemotherapy-induced damage. Neuropathy was induced in animals by paclitaxel injection (2.0 mg kg -1 i.p). DDD-028 (10 mg kg -1 ) and the reference drug, pregabalin (30 mg kg -1 ), were administered per os daily starting concomitantly with the first injection of paclitaxel and continuing 10 days after the end of paclitaxel treatment. The behavioural tests confirmed the antihyperalgesic efficacy of DDD-028 on paclitaxel-induced neuropathic pain. Furthermore, the electrophysiological analysis revealed the capacity of DDD-028 to restore near-normal sensory nerve conduction in paclitaxel-treated animals. Histopathology evidence indicated that DDD-028 was able to counteract effectively paclitaxel-induced peripheral neurotoxicity by protecting against the loss of intraepidermal nerve fibers, restoring physiological levels of neurofilament in nerve tissue and plasma, and preventing morphological alterations occurring in the sciatic nerves and dorsal root ganglia. Overall, DDD-028 is more effective than pregabalin in preventing chemotherapy-induced neurotoxicity. Thus, based on its potent antihyperalgesic and neuroprotective efficacy, DDD-028 seems to be a viable prophylactic medication to limit the development of neuropathies consequent to chemotherapy.

Pathophysiology and treatment of pain in multiple myeloma

Most patients with multiple myeloma (MM) suffer from chronic pain of varying degrees of intensity at every stage of the natural disease process. Osteolytic bone lesions are one of the most common complications of MM. The bone disease visualized by PET/CT and MRI affects up to 90% of newly diagnosed MM patients, increasing the risk of the development of skeletal-related events. Pathological fractures and spinal cord compression occur in 17% and 6% of patients, respectively. Bone pain is explained by an increase in pressure in the bone marrow, the release of chemical mediators by myeloma plasma cells, and the occurrence of microcracks in the bones, indirectly to a violation of local metabolism. Management of myeloma bone disease includes anti-myeloma chemotherapy and radiotherapy, antiresorptive therapy with bisphosphonates or denosumab, and direct pharmacological pain correction. Patients with pathological vertebral fractures and without spinal cord compression should be considered for vertebroplasty or kyphoplasty. The use of proteasome inhibitors and monoclonal antibodies for the treatment of MM is associated with a risk of herpes simplex virus (HSV) and varicella-zoster virus (VZV) reactivation. The result of the healing of herpetic eruptions in some patients will be the development of postherpetic neuralgia, manifested by excruciating pain for months or years. Moreover, the treatment with proteasome inhibitor bortezomib is often associated with the development of long-term persistent peripheral neuropathy, often complicated by pain. According to their neurobiological and clinical features, pain is classified into nociceptive, neuropathic, and functional. Bone pain is nociceptive and for postherpetic and chemotherapy-induced neuropathy, the neuropathic component is more significant. Opioids are the drugs of choice for moderate to severe nociceptive pain, while anticonvulsants and antidepressants are the most commonly used adjuvants for neuropathic pain. This review summarizes information on the pathophysiology of various types of pain syndrome in patients with MM, as well as on modern approaches to the prevention and treatment of complications. The issues of the pharmacology of opioid analgesics are discussed. The review concludes with data from a clinical trial of a new domestic non-opioid μ1-opioid receptor agonist Tafalgin, considered a real alternative to narcotic analgesics.

Peripheral Neuropathy Potentially Associated to Poly (ADP-Ribose) Polymerase Inhibitors: An Analysis of the Eudravigilance Database.

Poly (ADP-Ribose) polymerase inhibitors (PARPi) have emerged as a targeted therapy in cancer treatment with promising results in various types of cancer. This work aims to investigate the profile of adverse drug reactions (ADRs) associated with PARPi through the reports provided by the Eudravigilance (EV) database. We also intend to analyze the potential association of peripheral neuropathy to PARPi. Data on individual case safety reports (ICSRs) were obtained by accessing the European spontaneous reporting system via the EV website. A total of 12,762 ICSRs were collected from the EV database. Serious cases of nervous system disorders were analyzed providing strong evidence that peripheral neuropathy was reported in a higher frequency in patients treated with niraparib. Most cases reported a not recovered/not resolved outcome and involved drug withdrawal. However, several studies suggest that PARPi attenuate chemotherapy-induced painful neuropathy. Unexpected ADRs such as peripheral neuropathy may also occur, mostly in patients taking niraparib. Further pharmacovigilance studies should be conducted in this area to clarify with more precision the toxicity profile of these drugs.

Patient perspectives on consequences of resection for colorectal cancer: A qualitative study.

Colorectal cancer is diagnosed in approximately 500,000 patients each year in Europe, leading to a high number of patients having to cope with the consequences of resection for colorectal cancer. As treatment options tend to grow, more information on the effects of these treatments is needed to engage in shared decision-making. This study aims to explore the impact of resection for colorectal cancer on patients' daily life. Patients (≥18 years of age) who underwent an oncological colorectal resection between 2018 and 2021 were selected. Purposeful sampling was used to include patients who differed in age, comorbidity conditions, types of (neo)adjuvant therapy, postoperative complications and the presence/absence of a stoma. Semi-structured interviews were conducted, guided by a topic guide. Interviews were fully transcribed and subsequently thematically analysed using the framework approach. Analyses were carried out using the following predefined themes: (1) daily life and activities; (2) psychological functioning; (3) social functioning; (4) sexual functioning; and (5) healthcare experiences. Sixteen patients with a follow-up period of between 0.6 and 4.4 years after surgery were included in this study. Participants reported several challenges experienced because of poor bowel function, a stoma, chemotherapy-induced neuropathy, fear of recurrence and sexual dysfunction. However, they reported these as not interfering much with daily life. Colorectal cancer treatment leads to several challenges and treatment-related health deficits. This is often not recognized by generic patient-reported outcome measures, but the findings on treatment-related health deficits presented in this study contain valuable insights which might contribute to improving colorectal cancer care, shared decision making and value-based health care.

Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies - (lessons learned from) a prospective study.

This prospective cohort study aimed to characterise the impact of oxaliplatin-based chemotherapy and its neurotoxic side effects (i.e., chemotherapy-induced neuropathy) on functional fall-risk and falls. Twenty chemotherapy-naïve participants (mean age, 59 years; 16 males) were consecutively included. A multimodal fall risk assessment was performed at four time points within 6 months. Polyneuropathy was assessed using the Neurologic Disability Scale; the fall risk was assessed by functional tests (Tinetti Test, Chair-Rising Test, and Timed up and Go Test). Patient-reported outcomes comprised the Hospitality Anxiety and Depression Scale (HADS), the Falls Efficacy Scale - International (FES-I) to assess the fear of falling, and the Physical Activity for the Elderly (PASE) questionnaire. Three falls occurred during the study. All fallen participants had a high fall risk-index (≥4 more risk factors) compared to only 30% of the non-fallen participants (p = 0.03) and suffered more frequently from pre-existing mild polyneuropathy (p = 0.049). Study discontinuation (n = 12) was associated with a higher rate of polypharmacy (p = 0.045), anxiety (HADS-A, p = 0.03), and specific fear of falling (FES-I, p = 0.025). In contrast, study completers (n = 8) reported an improvement in physical activity (PASE) (p = 0.018). In summary, pre-existing fall-risk factors impacted more falls than chemotherapy. A fall risk index offers a time-efficient screening option in an outpatient oncological setting.

Calcium signaling in chemotherapy-induced neuropathy

Alterations in calcium (Ca2+) signaling is a major mechanism in the development of chemotherapy-induced peripheral neuropathy (CIPN), a side effect caused by multiple chemotherapy regimens. CIPN is associated with numbness and incessant tingling in hands and feet which diminishes quality of life during treatment. In up to 50% of survivors, CIPN is essentially irreversible. There are no approved, disease-modifying treatments for CIPN. The only recourse for oncologists is to modify the chemotherapy dose, a situation that can compromise optimal chemotherapy and impact patient outcomes. Here we focus on taxanes and other chemotherapeutic agents that work by altering microtubule assemblies to kill cancer cells, but also have off-target toxicities. There have been many molecular mechanisms proposed to explain the effects of microtubule-disrupting drugs. In neurons, an initiating step in the off-target effects of treatment by taxane is binding to neuronal calcium sensor 1 (NCS1), a sensitive Ca2+ sensor protein that maintains the resting Ca2+ concentration and dynamically enhances responses to cellular stimuli. The taxane/NCS1 interaction causes a Ca2+ surge that starts a pathophysiological cascade of consequences. This same mechanism contributes to other conditions including chemotherapy-induced cognitive impairment. Strategies to prevent the Ca2+ surge are the foundation of current work.

Insulin-like Growth Factor-1 (IGF-1) Related Drugs in Pain Management.

Objective. The aim of this review is to explore the role of IGF-1 and IGF-1R inhibitors in pain-related conditions and assess the effectiveness of IGF-1-related drugs in pain management. Specifically, this paper investigates the potential involvement of IGF-1 in nociception, nerve regeneration, and the development of neuropathic pain. Methods. We conducted a search of the PUBMED/MEDLINE database, Scopus, and the Cochrane Library for all reports published in English on IGF-1 in pain management from origination through November 2022. The resulting 545 articles were screened, and 18 articles were found to be relevant after reading abstracts. After further examination of the full text of these articles, ten were included in the analysis and discussion. The levels of clinical evidence and implications for recommendations of all the included human studies were graded. Results. The search yielded 545 articles, of which 316 articles were deemed irrelevant by reading the titles. There were 18 articles deemed relevant after reading abstracts, of which 8 of the reports were excluded due to lack of IGF-1-related drug treatment after reviewing the full text of the articles. All ten articles were retrieved for analysis and discussion. We found that IGF-1 may have several positive effects on pain management, including promoting the resolution of hyperalgesia, preventing chemotherapy-induced neuropathy, reversing neuronal hyperactivity, and elevating the nociceptive threshold. On the other hand, IGF-1R inhibitors may alleviate pain in mice with injury of the sciatic nerve, bone cancer pain, and endometriosis-induced hyperalgesia. While one study showed marked improvement in thyroid-associated ophthalmopathy in humans treated with IGF-1R inhibitor, two other studies did not find any benefits from IGF-1 treatment. Conclusions. This review highlights the potential of IGF-1 and IGF-1R inhibitors in pain management, but further research is needed to fully understand their efficacy and potential side effects.

Genetic variations that influence paclitaxel pharmacokinetics and intracellular effects that may contribute to chemotherapy-induced neuropathy: A narrative review.

Taxanes, particularly paclitaxel and docetaxel, are chemotherapeutic agents commonly used to treat breast cancers. A frequent side effect is chemotherapy-induced peripheral neuropathy (CIPN) that occurs in up to 70% of all treated patients and impacts the quality of life during and after treatment. CIPN presents as glove and stocking sensory deficits and diminished motor and autonomic function. Nerves with longer axons are at higher risk of developing CIPN. The causes of CIPN are multifactorial and poorly understood, limiting treatment options. Pathophysiologic mechanisms can include: (i) disruptions of mitochondrial and intracellular microtubule functions, (ii) disruption of axon morphology, and (iii) activation of microglial and other immune cell responses, among others. Recent work has explored the contribution of genetic variation and selected epigenetic changes in response to taxanes for any insights into their relation to pathophysiologic mechanisms of CIPN20, with the hope of identifying predictive and targetable biomarkers. Although promising, many genetic studies of CIPN are inconsistent making it difficult to develop reliable biomarkers of CIPN. The aims of this narrative review are to benchmark available evidence and identify gaps in the understanding of the role genetic variation has in influencing paclitaxel's pharmacokinetics and cellular membrane transport potentially related to the development of CIPN.

An efficient cellular image-based platform for high-content screening of neuroprotective agents against chemotherapy-induced neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect, with no approved therapy for prevention or treatment. Here, we aimed to establish a high-content image platform based on the neurite outgrowth of dorsal root ganglia (DRG)-derived neuron cells for the discovery of neuroprotective agents against paclitaxel-induced CIPN. ND7/23 cells, an immortalized hybrid DRG cell line, were maturely differentiated by induction with nerve growth factor and upregulation of intracellular cAMP levels. High-content image analyses of the neurofilament-stained neurite network showed that paclitaxel disrupted the neurite outgrowth of well-differentiated ND7/23 DRG neuron cells, recapitulating characteristic effects of paclitaxel on primary cultured DRG neurons. This process coincided with the upregulated activity of store-operated Ca2+ entry, similar to those found in rodent models of paclitaxel-induced CIPN. The previously identified neuroprotective agents, minoxidil and 8-Br-cyclic adenosine monophosphate ribose (8-Br-cADPR), attenuated the reduction in total neurite outgrowth in paclitaxel-damaged ND7/23 cells. Additionally, the total neurite outgrowth of well-differentiated ND7/23 cells was concentration-dependently reduced by the neurotoxic chemotherapeutic agents, oxaliplatin and bortezomib, but not the less neurotoxic 5-fluorouracil. We demonstrated that high-content analyses of neurite morphology in well-differentiated DRG neuron-derived cells provide an effective, reproducible, and high-throughput strategy for developing therapeutics against CIPN.

Nanotechnology Approaches for Prevention and Treatment of Chemotherapy-Induced Neurotoxicity, Neuropathy, and Cardiomyopathy in Breast and Ovarian Cancer Survivors.

Nanotechnology has emerged as a promising approach for the targeted delivery of therapeutic agents while improving their efficacy and safety. As a result, nanomaterial development for the selective targeting of cancers, with the possibility of treating off-target, detrimental sequelae caused by chemotherapy, is an important area of research. Breast and ovarian cancer are among the most common cancer types in women, and chemotherapy is an essential treatment modality for these diseases. However, chemotherapy-induced neurotoxicity, neuropathy, and cardiomyopathy are common side effects that can affect breast and ovarian cancer survivors quality of life. Therefore, there is an urgent need to develop effective prevention and treatment strategies for these adverse effects. Nanoparticles (NPs) have extreme potential for enhancing therapeutic efficacy but require continued research to elucidate beneficial interventions for women cancer survivors. In short, nanotechnology-based approaches have emerged as promising strategies for preventing and treating chemotherapy-induced neurotoxicity, neuropathy, and cardiomyopathy. NP-based drug delivery systems and therapeutics have shown potential for reducing the side effects of chemotherapeutics while improving drug efficacy. In this article, the latest nanotechnology approaches and their potential for the prevention and treatment of chemotherapy-induced neurotoxicity, neuropathy, and cardiomyopathy in breast and ovarian cancer survivors are discussed.