Study of the relationship between psychoactive substance use and pain in cancer patients and cancer survivors: A French nationwide cross-sectional study.

Pain is a prevalent symptom among cancer patients and survivors. Psychoactive substance use (PSU) is associated with both the presence and severity of pain. However, little is known about this association in the context of cancer. The primary objective was to compare the prevalence of PSU and its relationship with pain during and after cancer. PSU was defined as the use of nonmedication substances (alcohol, tobacco, e-cigarettes, cannabidiol, and cannabis), with frequency categorized as at least yearly, monthly, weekly, or daily. Secondary objectives aimed to explore the relationships between PSU and pain characteristics, health-related quality of life, anxiety, depression, deprivation, and individual characteristics. Among the 1041 individuals included, pain prevalence was 44.7% (95% confidence interval [CI] 41.6%-47.8%). The overall prevalence of PSU at least monthly was 67.0% (95% CI 64.0%-69.8%). The proportions of chronic and neuropathic pains were higher for at least monthly use of cannabidiol compared to nonuse (70.0% vs. 39.3% and 55.7% vs. 28.1%, p < .001). In multivariate analysis, the monthly uses of tobacco and cannabidiol were higher in painful individuals than in nonpainful ones (odds ratio: 2.85 [95% CI 1.22-6.64] and 3.76 [95% CI 1.13-12.44], p < .05). From the point of view of the patient care, the study underscores the need for physicians to prioritize smoking cessation and pay attention to the use of cannabidiol during and after cancer.

Motor disorders related to oxaliplatin-induced peripheral neuropathy: long-term severity and impact on quality of life.

PURPOSE: Sensory chemotherapy-induced peripheral neuropathy (CIPN) is well-recognized, but motor CIPN remains understudied. This secondary analysis focused on the long-term severity and impact of motor disorders, their relation to sensory CIPN, neuropathic pain, psychological distress, and health-related quality of life (HRQoL) after oxaliplatin-based chemotherapy in colorectal cancer (CRC) survivors. METHODS: Data from a multicenter, cross-sectional study were re-analyzed to explore motor CIPN among CRC survivors up to 5 years post-chemotherapy, with no longitudinal follow-up. Questionnaires assessed sensory and motor CIPN (QLQ-CIPN20), neuropathic pain (DN4), anxiety and depression (HADS), and HRQoL (QLQ-C30). RESULTS: Among 405 CRC survivors, 31.1% had sensory CIPN as previously described. When categorizing the 405 CRC survivors based on the years since their last oxaliplatin-based chemotherapy, the motor scores derived from the QLQ-CIPN20 showed no significant difference between years (p = 0.08). Motor CIPN scores correlated with female gender, higher oxaliplatin dose intensity, sensory CIPN, and neuropathic pain. Motor CIPN also linked to decreased HRQoL and increased psychological distress. CONCLUSION: The study underscores the detrimental impact of motor disorders on CRC survivors post-oxaliplatin-based chemotherapy. Oncologists should prioritize assessing and managing motor manifestations alongside sensory symptoms to enhance post-cancer quality of life. TRIAL REGISTRATION: NCT02970526 (2016-11-22). https://classic. CLINICALTRIALS: gov/ct2/show/NCT02970526?term=NCT02970526&draw=2&rank=1 .

Efficacy of donepezil for the treatment of oxaliplatin-induced peripheral neuropathy: DONEPEZOX, a protocol of a proof of concept, randomised, triple-blinded and multicentre trial.

BACKGROUND: The use of oxaliplatin in digestive tract cancers could induce severe peripheral neuropathy (OIPN) decreasing the quality of life of patients and survivors. There is currently, no univocal treatment for these peripheral neuropathies. Donepezil, a reversible inhibitor of cholinesterase, used to treat Alzheimer's disease and dementia, is reported to have a good safety profile in humans, and preclinical data have provided initial evidence of its effectiveness in diminishing neuropathic symptoms and related comorbidities in OIPN animal models. METHODS: The DONEPEZOX trial will be a proof-of-concept, randomised, triple-blinded, and multicentre study. It will be the first clinical trial evaluating the efficacy and safety of donepezil for the management of OIPN. Adult cancer survivors with OIPN that report sensory neuropathy according to QLQ-CIPN20 sensory score (equivalence of a grade ≥ 2), at least 6 months after the end of an oxaliplatin-based chemotherapy will be included. Eighty patients will be randomly assigned to receive either donepezil or placebo over 16 weeks of treatment. The primary endpoint will be the rate of responders (neuropathic grade decreases according to the QLQ-CIPN20 sensory score) in the donepezil arm. The severity of OIPN will be assessed by the QLQ-CIPN20 sensory scale before and after 16 weeks of treatment. The comparison versus the placebo arm will be a secondary objective. The other secondary endpoints will be tolerance to donepezil, the severity and features of OIPN in each arm before and after treatment, related-comorbidities and quality of life. Fleming's one-stage design will be used for sample size estimation. This design yields a type I error rate of 0.0417 and power of 91% for a responder rate of at least 30% in donepezil arm. A total of 80 randomized patients is planned. DISCUSSION: This study will allow, in the case of positive results, to initiate a phase 3 randomized and placebo-controlled (primary endpoint) clinical study to assess the therapeutic interest of donepezil to treat OIPN. TRIAL REGISTRATION: NCT05254639 , clincialtrials.gov, Registered 24 February 2022.

Relation between auditory difficulties and bortezomib-induced peripheral neuropathy in multiple myeloma: a single-center cross-sectional study.

PURPOSE: Bortezomib is a neurotoxic drug used in multiple myeloma and responsible for chemotherapy-induced peripheral neuropathy (CIPN). In a previous cross-sectional study, CIPN prevalence was about 26.9% in 67 patients. A second data analysis was performed to explore the relation between CIPN and auditory difficulties. METHODS: Based on 66 multiple myeloma patients from a single center, auditory difficulties were assessed with a self-questionnaire and compared to sensory CIPN (QLQ-CIPN20 questionnaire), patients' characteristics and anticancer treatments. RESULTS: The prevalence of auditory difficulties was about 42.4% (95% CI [30.6-55.2]) of the 66 patients analyzed and was higher in patients with CIPN than without (82.4% vs. 28.6%, p < 0.001). Auditory difficulties were not related to the characteristics of patients and treatments. The severity of auditory difficulties were correlated to CIPN severity (spearman's coefficient: 0.49, p = 0.009). Odds-ratio of auditory difficulties (multivariable analysis adjusted for sensory CIPN, recreation or professional noise exposure, gender, age, and treatments) was significantly associated with CIPN (18.7, 95% CI [3.0-117.1], p = 0.002). CONCLUSION: This relation between CIPN and auditory difficulties raises concerns about hearing safety in multiple myeloma patients treated by bortezomib. TRIAL REGISTRATION NUMBER: NCT03344328.

A new clinically-relevant rat model of letrozole-induced chronic nociceptive disorders.

Among postmenopausal women with estrogen receptor-positive breast cancer, more than 80% receive hormone therapy including aromatase inhibitors (AIs). Half of them develop chronic arthralgia - characterized by symmetric articular pain, carpal tunnel syndrome, morning stiffness, myalgia and a decrease in grip strength - which is associated with treatment discontinuation. Only a few animal studies have linked AI treatment to nociception, and none to arthralgia. Thus, we developed a new chronic AI-induced nociceptive disorder model mimicking clinical symptoms induced by AIs, using subcutaneous letrozole pellets in ovariectomized (OVX) rats. Following plasma letrozole dosage at the end of the experiment (day 73), only rats with at least 90 ng/ml of letrozole were considered significantly exposed to letrozole (OVX + high LTZ group), whereas treated animals with less than 90 ng/ml were pooled in the OVX + low LTZ group. Chronic nociceptive disorder set in rapidly and was maintained for more than 70 days in the OVX + high LTZ group. Furthermore, OVX + high LTZ rats saw no alteration in locomotion, myalgia or experimental anxiety during this period. Bone parameters of the femora were significantly altered in all OVX rats compared to Sham+vehicle pellet. A mechanistic analysis focused on TRPA1, receptor suspected to mediate AI-evoked pain, and showed no modification in its expression in the DRG. This new long-lasting chronic rat model, efficiently reproduces the symptoms of AI-induced nociceptive disorder affecting patients' daily activities and quality-of-life. It should help to study the pathophysiology of this disorder and to promote the development of new therapeutic strategies.

Prevention, diagnosis and management of chemotherapy-induced peripheral neuropathy: a cross-sectional study of French oncologists' professional practices.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is challenging for oncologists. Many publications mention the high incidence of CIPN and the lack of effective preventive/management strategies and robust diagnostic tools. This cross-sectional study was aimed at assessing the practice of French oncologists for CIPN prevention, diagnosis and management. METHODS: This web-based survey was sent to French oncologists by the regional cancer networks. Incidence and impact of CIPN were assessed using visual analogue scales (VAS) and diagnostic strategies were recorded. Also recorded were the drugs used to prevent or manage CIPN and their perceived efficacy and safety (VAS). RESULTS: Among the 210 oncologists included, the perceived incidence of CIPN was about 36.2 ± 22.1% of patients. About 99.5% of oncologists declared that they assess CIPN during medical follow-up. The use of drugs to prevent CIPN was reported by 9.6% of oncologists (group B vitamins (35.0%) and calcium and magnesium infusion (25.0%)). In the case of CIPN, the therapeutic adjustment of neurotoxic anticancer drugs is performed by 99.0% of oncologists (chemotherapy change (49.8%), dose reduction (30.9%) or interruption (19.3%)). The pharmacological management of CIPN was declared by 72.9% of oncologists. The main drugs used are pregabalin (75.8%), amitriptyline (32.7%) and gabapentin (25.5%). Duloxetine (ASCO recommendation) is used by only 11.8% of oncologists. CONCLUSION: Oncologists were clearly aware of CIPN risks, but its incidence tended to be underestimated and the ASCO recommendations for the management of CIPN were not followed. The prevention, diagnosis and management of CIPN remain problematic in clinical practice in France. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03854864.

Clinical and Organizational Impact of the AIRSEAL® Insufflation System During Laparoscopic Surgery: A Systematic Review.

Several low-impact laparoscopic strategies have been developed to improve the safety of pneumoperitoneum. We conducted a systematic review to establish the current evidence base for the use of the AIRSEAL® insufflation device for low-pressure pneumoperitoneum in laparoscopic surgery. We searched the literature using several electronic databases, for studies with comparative design published in the English language from January 2010 to April 2020. The population of interest included patients with any type of health condition who underwent laparoscopic surgery using the AIRSEAL® insufflation system or a standard CO2 insufflator. Ten studies (four randomized clinical trials/six non-randomized clinical trials), that enrolled 1394 participants in total who underwent urology, gynaecology or abdominal surgeries, were included. Total complication rates were similar between groups. Only three studies evaluated the impact of the insufflation system on post-operative pain, and showed inconsistent benefit of AIRSEAL® (significant decrease in pain in two studies, no difference in one). The same was observed in the two sole studies in which pain killers consumption was measured (significant decrease in morphine consumption 24 h after surgery in one study, no difference in the other). Operative duration was significantly shorter with AIRSEAL® in three studies. For both post-operative room and total length of stay, there was no difference between groups. No studies reported economic outcomes. Current literature supports the feasibility of the AIRSEAL® system during laparoscopic surgery but more studies are required to establish the added clinical benefit and to explore the preferences of physicians and patients.

Perception of pharmacy students toward opioid-related disorders and roles of community pharmacists: A French nationwide cross-sectional study.

Background: Community pharmacists are among the frontline health professionals who manage patients with an opioid-related disorder (ORD). Pharmacists frequently have a negative attitude toward these patients, which could have a negative impact on their management. However, education on ORD may improve the attitude of future healthcare professionals. This cross-sectional study aimed to assess French pharmacy students' perceptions of ORD. Methods: This online survey was performed by emails sent to French pharmacy schools (between January 14, 2019 and May 31, 2019). The primary outcome was the perception (visual analogic scale) of ORD as a disease, the roles of community pharmacies (delivery of opioid agonist therapy-OAT and harm reduction kits), and the efficacy of OAT. The secondary outcomes assessed professional experience, university experience of and education on ORD, and the individual characteristics of students. Results: Among the 1,994 students included, 76.3% perceived ORD as a disease and felt that it was normal for pharmacists to deliver OAT (78.9%) and harm reduction kits (74.6%). However, only 46.9% perceived OAT as being effective. Multivariable analyses showed that females had a more positive perception in recognizing ORD as a disease. The progression through university years increased the positive perception of ORD as a disease and the delivery of OAT and harm reduction kits by pharmacists. Education on substance-related disorders had no impact on any scores. Students who had already delivered OAT had a negative perception of their efficacy. The students who had already performed pharmacy jobs or traineeships had a negative perception of harm reduction kit delivery. Conclusion: Education on substance-related disorders had no impact on students' perceptions. It seemed that the maturity acquired through university years had a stronger impact on the students' perceptions of ORD. Efforts must be made to improve our teaching methods and reinforce the confidence of students in the roles of community pharmacists.

The Class I HDAC Inhibitor, MS-275, Prevents Oxaliplatin-Induced Chronic Neuropathy and Potentiates Its Antiproliferative Activity in Mice.

Oxaliplatin, the first-line chemotherapeutic agent against colorectal cancer (CRC), induces peripheral neuropathies, which can lead to dose limitation and treatment discontinuation. Downregulation of potassium channels, which involves histone deacetylase (HDAC) activity, has been identified as an important tuner of acute oxaliplatin-induced hypersensitivity. MS-275, a class I histone deacetylase inhibitor (HDACi), prevents acute oxaliplatin-induced peripheral neuropathy (OIPN). Moreover, MS-275 exerts anti-tumor activity in several types of cancers, including CRC. We thus hypothesized that MS-275 could exert both a preventive effect against OIPN and potentially a synergistic effect combined with oxaliplatin against CRC development. We first used RNAseq to assess transcriptional changes occurring in DRG neurons from mice treated by repeated injection of oxaliplatin. Moreover, we assessed the effects of MS-275 on chronic oxaliplatin-induced peripheral neuropathy development in vivo on APCMin/+ mice and on cancer progression when combined with oxaliplatin, both in vivo on APCMin/+ mice and in a mouse model of an orthotopic allograft of the CT26 cell line as well as in vitro in T84 and HT29 human CRC cell lines. We found 741 differentially expressed genes (DEGs) between oxaliplatin- and vehicle-treated animals. While acute OIPN is known as a channelopathy involving HDAC activity, chronic OIPN exerts weak ion channel transcriptional changes and no HDAC expression changes in peripheral neurons from OIPN mice. However, MS-275 prevents the development of sensory neuropathic symptoms induced by repeated oxaliplatin administration in APCMin/+ mice. Moreover, combined with oxaliplatin, MS-275 also exerts synergistic antiproliferative and increased survival effects in CT26-bearing mice. Consistently, combined drug associations exert synergic apoptotic and cell death effects in both T84 and HT29 human CRC cell lines. Our results strongly suggest combining oxaliplatin and MS-275 administration in CRC patients in order to potentiate the antiproliferative action of chemotherapy, while preventing its neurotoxic effect.

Warmed and humidified carbon dioxide for abdominal laparoscopic surgery: meta-analysis of the current literature.

BACKGROUND: The creation of a pneumoperitoneum for laparoscopic surgery is performed by the insufflation of carbon dioxide (CO2). The insufflated CO2 is generally at room temperature (20-25 °C) and dry (0-5 % relative humidity). However, these physical characteristics could lead to alterations of the peritoneal cavity, leading to operative and postoperative complications. Warming and humidifying the insufflated gas has been proposed to reduce the iatrogenic effects of laparoscopic surgery, such as pain, hypothermia and peritoneal alterations. Two medical devices are currently available for laparoscopic surgery with warm and humidified CO2. METHODS: Clinical studies were identified by searching PubMed with keywords relating to humidified and warmed CO2 for laparoscopic procedures. Analysis of the literature focused on postoperative pain, analgesic consumption, duration of hospital stay and convalescence, surgical techniques and hypothermia. RESULTS: Bibliographic analyses reported 114 publications from 1977 to 2015, with only 17 publications of clinical interest. The main disciplines focused on were gynaecological and digestive surgery ). Analysis of the studies selected reported only a small beneficial effect of warmed and humidified laparoscopy compared to standard laparoscopy on immediate postoperative pain and per procedure hypothermia. No difference was observed for later postoperative shoulder pain, morphine equivalent daily doses, postoperative body core temperature, recovery room and hospital length of stay, lens fogging and procedure duration. CONCLUSIONS: Only few beneficial effects on immediate postoperative pain and core temperature have been identified in this meta-analysis. Although more studies are probably needed to close the debate on the real impact of warmed and humidified CO2 for laparoscopic procedures.

Cholinergic Neurotransmission in the Posterior Insular Cortex Is Altered in Preclinical Models of Neuropathic Pain: Key Role of Muscarinic M2 Receptors in Donepezil-Induced Antinociception.

Neuropathic pain is one of the most debilitating pain conditions, yet no therapeutic strategy has been really effective for its treatment. Hence, a better understanding of its pathophysiological mechanisms is necessary to identify new pharmacological targets. Here, we report important metabolic variations in brain areas involved in pain processing in a rat model of oxaliplatin-induced neuropathy using HRMAS (1)H-NMR spectroscopy. An increased concentration of choline has been evidenced in the posterior insular cortex (pIC) of neuropathic animal, which was significantly correlated with animals' pain thresholds. The screening of 34 genes mRNA involved in the pIC cholinergic system showed an increased expression of the high-affinity choline transporter and especially the muscarinic M2 receptors, which was confirmed by Western blot analysis in oxaliplatin-treated rats and the spared nerve injury model (SNI). Furthermore, pharmacological activation of M2 receptors in the pIC using oxotremorine completely reversed oxaliplatin-induced mechanical allodynia. Consistently, systemic treatment with donepezil, a centrally active acetylcholinesterase inhibitor, prevented and reversed oxaliplatin-induced cold and mechanical allodynia as well as social interaction impairment. Intracerebral microdialysis revealed a lower level of acetylcholine in the pIC of oxaliplatin-treated rats, which was significantly increased by donepezil. Finally, the analgesic effect of donepezil was markedly reduced by a microinjection of the M2 antagonist, methoctramine, within the pIC, in both oxaliplatin-treated rats and spared nerve injury rats. These findings highlight the crucial role of cortical cholinergic neurotransmission as a critical mechanism of neuropathic pain, and suggest that targeting insular M2 receptors using central cholinomimetics could be used for neuropathic pain treatment. SIGNIFICANCE STATEMENT: Our study describes a decrease in cholinergic neurotransmission in the posterior insular cortex in neuropathic pain condition and the involvement of M2 receptors. Targeting these cortical muscarinic M2 receptors using central cholinomimetics could be an effective therapy for neuropathic pain treatment.

Assessment of thermal sensitivity in rats using the thermal place preference test: description and application in the study of oxaliplatin-induced acute thermal hypersensitivity and inflammatory pain models.

Thermal sensitivity is an essential characteristic of some painful states, including oxaliplatin-induced neuropathy. The thermal place preference test (TPPT) was designed to finely assess thermal sensitivity in rodents. The TPPT monitors the time spent by unrestrained rodents on a test plate at fixed temperatures (5-50°C) compared with an adjacent reference plate at a neutral temperature (25°C). Here, we report the results of a study designed (i) to validate the optimal methodological parameters for measuring thermal sensitivity in rats, (ii) to assess the thermal sensitivity of healthy rats and animal models of pain and (iii) to explore the pharmacological effects of analgesic drugs. The most reproducible conditions occurred when the TPPT was performed in the morning and in the dark for 3 min with the reference plate set to 25°C. The temperature preferences of healthy rats were more than 17°C and less than 40°C. When compared with control animals, oxaliplatin-treated rats showed thermal hypersensitivity at 12, 20 and 35°C, and carrageenan-treated rats showed thermal hypersensitivity at 15 and 45°C. Duloxetine (2.5 mg/kg, intraperitoneal) reversed oxaliplatin-induced cold hypersensitivity (20°C) and morphine (1 mg/kg, intravenous) reversed carrageenan-induced heat hypersensitivity (45°C). We conclude that the TPPT enables a fine-grained assessment of thermal sensitivity that is relevant to the pathophysiological exploration of animal pain models and to the pharmacological assessment of analgesic drugs.

Comparison of the microvascular anastomotic Coupler™ system with hand-sewn suture for end to end veno-venous anastomosis for head and neck reconstruction with free flap transfer: Medico-economic retrospective case-control study.

The aim of this study was to assess the medico-economic impact of the MACD Coupler™ system in comparison with HSA for end to end veno-venous anastomosis during free flap transfer. A retrospective case-control study was performed in an academic institution, from March 2019 through July 2021, to analyze medical and economic outcomes of patients managed for head and neck reconstruction with free flap transfer. 43 patients per group were analyzed. Rates of initial success, re-intervention, complications and flap transfer failure were not different between groups. Use of MACD increased the cost of medical devices between Coupler and Control groups with respectively K€ 0.7 [0.5; 0.8] and K€ 0.1 [0.5; 0.8] (p = 0.001) and decreased the cost for operating staff with respectively K€ 4.0 [3.4; 5.2] and K€ 5.1 [3.8; 5.4] (p = 0.03). The total management costs were not different between groups with respectively a total median cost of K€ 18.4 [14.3; 27.2] and K€ 17.3 [14.1; 23.7] (p = 0.03). In conclusion, the cost of the Coupler™ is significant but is partly offset by the decrease in operating staff costs. The choice of one or the other technique can be left to the discretion of the surgeon.

Emerging trends in understanding chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major concern in oncology practice given the increasing number of cancer survivors and the lack of effective treatment. The incidence of peripheral neuropathy depends upon the anticancer drug used, but is commonly under-reported in clinical trials. Several animal models have been developed in an attempt to better characterize the pathophysiological mechanisms underlying these CIPN and to find more specific treatments. Over the past two decades, three main trends have emerged from preclinical research on CIPN. There is a compelling body of evidence that neurotoxic anticancer drugs affect the peripheral sensory nerve by directly targeting the mitochondria and producing oxidative stress, by functionally impairing the ion channels and/or by triggering immunological mechanisms through the activation of satellite glial cells. These various neurotoxic events may account for the lack of effective treatment, as neuroprotection may probably only be achieved using a polytherapy that targets all of these mechanisms. The aim of this review is to describe the clinical features of CIPN and to summarize the recent trends in understanding its pathophysiology.

Use of permacol in parietal and general surgery: a bibliographic review.

BACKGROUND: The use of synthetic meshes on infected incisional hernias often fails and is therefore contraindicated. Biological meshes offer a novel solution. Among them, Permacol requires a bibliographic analysis of its efficacy and tolerance. DESIGN: A bibliographic analysis was carried out on the efficacy and tolerance of Permacol in parietal and general surgery. RESULTS: A total of 22 publications described the use of Permacol in digestive surgery. The advantages of Permacol would be usability in contaminated surgical fields, biocompatibility, no erosion of intestinal wall, and less risk of adhesions. The main drawback of Permacol is its high cost. CONCLUSION: Even so, Permacol can play an important part in the short-term management of complex or contaminated abdominal wall defects. The lack of long-term studies and the high cost of the implant call for a medical cost-effectiveness assessment to determine the indications for Permacol in parietal and general surgery.

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 α4ß2 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.

Self-Medication during and after Cancer: A French Nation-Wide Cross-Sectional Study.

(1) Background: Little data are available in Western countries regarding self-medication practices in the context of cancer. The aim of this study was to describe the prevalence of self-medication practices during (cancer patients) and after cancer (cancer survivors). (2) Methods: This multicenter, cross-sectional, and online study was designed to assess self-medication prevalence. Other objectives were explored, notably the medication types, the perceived risks, and the relation with symptoms and quality of life. (3) Results: Among the 518 patients analyzed, 56.4% declared they practiced self-medication. Dietary supplements and pain medications were used by more than half of the patients. Self-medication was practiced in order to manage the adverse effects of anticancer therapies (63.8%), for which pain was the leading indication (39%), and to improve the efficacy of anticancer therapies (43.8%, cancer patients). Patients believed that self-medication could not lead to drug interactions with anticancer therapies (84.9%, cancer patients), or to adverse effects (84.6%, cancer patients and survivors). Self-medication practices were associated with altered social functioning, pain, insomnia, and financial difficulties. (4) Conclusions: Self-medication was performed by more than half of the responders (ongoing or past cancer) and could be a marker of the undermanagement of cancer and treatment-related adverse effects.

Exploring Serum Biomarkers for Neuropathic Pain in Rat Models of Chemotherapy-Induced Peripheral Neuropathy: A Comparative Pilot Study with Oxaliplatin, Paclitaxel, Bortezomib, and Vincristine.

Blood biomarkers, including neurofilament light chain (NfL), have garnered attention as potential indicators for chemotherapy-induced peripheral neuropathy (CIPN), a dose-limiting adverse effect of neurotoxic anticancer drugs. However, no blood biomarker has been established for routine application or translational research. This pilot study aimed to evaluate a limited panel of blood biomarkers in rat models of CIPN and their correlations with neuropathic pain. CIPN models were induced through repeated injections of oxaliplatin, paclitaxel, bortezomib, and vincristine. Electronic von Frey testing was used to assess tactile allodynia. Post anticancer injections, serum concentrations of 31 proteins were measured. Allodynia thresholds decreased in anticancer-treated animals compared to controls. No consistent modifications were observed in the biomarkers across CIPN models. The most noteworthy biomarkers with increased concentrations in at least two CIPN models were NfL (paclitaxel, vincristine), MCP-1, and RANTES (oxaliplatin, vincristine). Vincristine-treated animals exhibited strong correlations between LIX, MCP-1, NfL, and VEGF concentrations and tactile allodynia thresholds. No single biomarker can be recommended as a unique indicator of CIPN-related pain. Because of the study limitations (single dose of each anticancer drug, young animals, and single time measurement of biomarkers), further investigations are necessary to define the kinetics, specificities, and sensitivities of MCP-1, RANTES, and NfL.

Neurofilament light chain in plasma as a sensitive diagnostic biomarker of peripheral neurotoxicity: In Vivo mouse studies with oxaliplatin and paclitaxel - NeuroDeRisk project.

Identifying compounds that are neurotoxic either toward the central or the peripheral nervous systems (CNS or PNS) would greatly benefit early stages of drug development by derisking liabilities and selecting safe compounds. Unfortunately, so far assays mostly rely on histopathology findings often identified after repeated-dose toxicity studies in animals. The European NeuroDeRisk project aimed to provide comprehensive tools to identify compounds likely inducing neurotoxicity. As part of this project, the present work aimed to identify diagnostic non-invasive biomarkers of PNS toxicity in mice. We used two neurotoxic drugs in vivo to correlate functional, histopathological and biological findings. CD1 male mice received repeated injections of oxaliplatin or paclitaxel followed by an assessment of drug exposure in CNS/PNS tissues. Functional signs of PNS toxicity were assessed using electronic von Frey and cold paw immersion tests (oxaliplatin), and functional observational battery, rotarod and cold plate tests (paclitaxel). Plasma concentrations of neurofilament light chain (NF-L) and vascular endothelial growth factor A (VEGF-A) were measured, and histopathological evaluations were performed on a comprehensive list of CNS and PNS tissues. Functional PNS toxicity was observed only in oxaliplatin-treated mice. Histopathological findings were observed dose-dependently only in paclitaxel groups. While no changes of VEGF-A concentrations was recorded, NF-L concentrations were increased only in paclitaxel-treated animals as early as 7 days after the onset of drug administration. These results show that plasma NF-L changes correlated with microscopic changes in the PNS, thus strongly suggesting that NF-L could be a sensitive and specific biomarker of PNS toxicity in mice.