Mindfulness is associated with severity of peripheral neuropathy and related patient-reported outcomes among colorectal cancer patients.

PURPOSE: Despite the detrimental impact of chronic (chemotherapy-induced) peripheral neuropathy PN on patients' lives, treatment options remain limited. We examined the association between mindfulness and chronic PN symptom severity and impairments in related patient-reported outcomes (PROs) among colorectal cancer (CRC) patients up to 2 years after diagnosis. METHODS: Newly diagnosed stage I-IV CRC patients from four Dutch hospitals were eligible for participation. Patients (N = 336) completed a questionnaire on mindfulness (MAAS) at 1 year after diagnosis, and questionnaires on sensory (SPN) and motor peripheral neuropathy (MPN) (EORTC QLQ-CIPN20), anxiety and depressive symptoms (HADS), sleep quality (PSQI), and fatigue (EORTC QLQ-C30) before initial treatment (baseline) and 1 and 2 years after diagnosis. RESULTS: At 1-year follow-up, 115 patients (34%) and 134 patients (40%), respectively, reported SPN or MPN symptoms. In multivariable regression analyses, higher mindfulness at 1-year follow-up was associated with less severe MPN and fewer anxiety and depressive symptoms, better sleep quality, and less fatigue. Of the patients with SPN or MPN at 1-year follow-up, symptoms had not returned to baseline level at 2-year follow-up in 59 (51%) and 72 (54%) patients, respectively. In this subgroup, higher mindfulness was associated with less severe SPN and fewer anxiety symptoms, depressive symptoms, and fatigue at 2-year follow-up. CONCLUSION: Mindfulness was associated with less severe PN and better related PROs among CRC patients with chronic PN. More research is needed to examine the role of mindfulness in the transition from acute to chronic PN.

Evaluating patient-reported symptoms and late adverse effects following completion of first-line chemotherapy for ovarian cancer using the MOST (Measure of Ovarian Symptoms and Treatment concerns).

OBJECTIVES: Knowledge on the course of symptoms patients with ovarian cancer experience is limited. We documented the prevalence and trajectories of symptoms after first-line chemotherapy using the Measure of Ovarian Symptoms and Treatment concerns (MOST). METHODS: A total of 726 patients who received platinum-based chemotherapy for ovarian cancer were asked to complete the MOST every 3 months, beginning 6 months post-diagnosis and continuing for up to 4 years. We used descriptive statistics to examine temporal changes in MOST-S26 index scores for disease or treatment-related (MOST-DorT), neurotoxicity (MOST-NTx), abdominal (MOST-Abdo), and psychological (MOST-Psych) symptoms, and wellbeing (MOST-Wellbeing) and selected individual symptoms. We used group-based trajectory models to identify groups with persistently poor symptoms. RESULTS: The median MOST-Abdo, MOST-DorT and MOST-Wellbeing score were worst at chemotherapy-end but improved and stabilised by 1, 3 and 12 months after treatment, respectively. The median MOST-NTx score peaked at 1 month after treatment before improving, while the median MOST-Psych score did not change substantially over time. Long-term moderate-to-severe fatigue (32%), trouble sleeping (31%), sore hands and feet (21%), pins and needles (20%) and anxiety (18%) were common. Trajectory models revealed groups of patients with persistent symptoms had MOST-DorT scores above 30 and MOST-NTx scores above 40 at treatment-end. CONCLUSIONS: Although many patients report improvements in symptoms by 3 months after first-line chemotherapy for ovarian cancer, patients who score > 30/100 on MOST-S26-DorT or > 40/100 on MOST-S26-NTx at the end of chemotherapy are likely to have persistent symptoms. The MOST could triage this at-risk subset for early intervention.

Concordance between Self-reported Symptoms and Clinically Ascertained Peripheral Neuropathy among Childhood Cancer Survivors: the St. Jude Lifetime Cohort Study.

BACKGROUND: Childhood cancer survivors are at elevated risk for motor and/or sensory neuropathy. The study aims to evaluate the concordance between self-report peripheral neuropathy compared with clinically ascertained peripheral neuropathy, and to identify factors associated with misclassification of peripheral neuropathy among survivors. METHODS: The concordance between self-report and clinically ascertained peripheral neuropathy was evaluated among 2,933 5+ years old childhood cancer survivors (mean age 33.3, SD = 8.9). The sensitivity, specificity, and accuracy of self-report peripheral motor neuropathy (PMN) and peripheral sensory neuropathy (PSN) were calculated with reference to clinically assessed peripheral neuropathy. RESULTS: Female survivors were more likely than male survivors to have clinically ascertained PMN (8.4% vs. 5.6%, P = 0.004). For females, having either PSN or PMN the most sensitive, specific, and accurate self-reported symptom was endorsing ≥2 symptoms on the self-report questionnaire (43.2%, 90.3%, and 85.2%, respectively), with kappa of 0.304. For males, having either PSN or PMN the most sensitive, specific, and accurate self-reported symptom was endorsing ≥2 symptoms on the self-report questionnaire (38.8%, 90.5%, and 86.3%, respectively) with kappa of 0.242. Age at diagnosis, emotional distress, and reporting pain in legs in the past 4 weeks were associated with an increased risk for false-positive reporting of peripheral neuropathy. Race (White), age at assessment, and emotional distress were associated with increased risk for false-negative reporting of peripheral neuropathy. CONCLUSIONS: Agreement between self-report and clinically ascertained peripheral neuropathy was poor in survivors. Choosing self-report versus clinical ascertained peripheral neuropathy should be carefully considered. IMPACT: The current study identifies the need for a self-report questionnaire that accurately assesses symptoms of peripheral neuropathy among cancer survivors.

Chemotherapy-induced peripheral neuropathy is promoted by enhanced spinal insulin-like growth factor-1 levels via astrocyte-dependent mechanisms.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and intractable complication in chemotherapy-receiving patients. Insulin-like growth factor-1 (IGF-1) is a popular neurotrophin with various functions, such as maintaining neuronal survival and synaptic functioning in the central nervous system. Therefore, we hypothesized that the IGF-1 signaling pathway could be a candidate target for treating CIPN. METHODS: We established the CIPN model by injecting mice intraperitoneally with oxaliplatin and assessed IGF-1 protein expression, its receptor IGF1R, phospho-IGF1R (p-IGF1R), interleukin-17A (IL-17A), tumor necrosis factor-α (TNF-α), and calcitonin gene-related peptide (CGRP) in the lumbar spinal cord with Western blot and immunofluorescence. To examine the effect of IGF-1 signaling on CIPN, we injected mice intrathecally or intraperitoneally with mouse recombinant IGF-1 (rIGF-1). RESULTS: IGF-1 protein expression decreased significantly in the spinal cord on D3 and D10 (the 3rd and 10th days after beginning oxaliplatin chemotherapy) and was co-localized with astrocytes primarily in the lumbar spinal cord, whereas IGF1R was predominantly expressed on neurons. Both intrathecally- and intraperitoneally-administered rIGF-1 relieved the chemotherapy-induced pain-like behavior and reduced IL-17A, TNF-α, and CGRP protein expressions in the spinal cord. CONCLUSION: Our results indicate a vital role for IGF-1 signaling in CIPN. Targeting IGF-1 signaling could be a potent therapeutic strategy for treating CIPN in clinical settings.

Yoga for cancer survivors with chemotherapy-induced peripheral neuropathy: Health-related quality of life outcomes.

BACKGROUND: Yoga is a meditative movement therapy focused on mind-body awareness. The impact of yoga on health-related quality of life (HRQOL) outcomes in patients with chemotherapy-induced peripheral neuropathy (CIPN) is unclear. METHODS: We conducted a pilot randomized wait-list controlled trial of 8 weeks of yoga (n = 21) versus wait-list control (n = 20) for CIPN in 41 breast and gynecological cancer survivors with persistent moderate to severe CIPN. HRQOL endpoints were Hospital Anxiety and Depression Scale (HADS), Brief Fatigue Inventory (BFI), and Insomnia Severity Index (ISI). The Treatment Expectancy Scale (TES) was administered at baseline. We estimated mean changes and 95% confidence intervals (CIs) from baseline to weeks 8 and 12 and compared arms using constrained linear mixed models. RESULTS: At week 8, HADS anxiety scores decreased -1.61 (-2.75, -0.46) in the yoga arm and -0.32 (-1.38, 0.75) points in the wait-list control arm (p = 0.099). At week 12, HADS anxiety scores decreased -1.42 (-2.57, -0.28) in yoga compared to an increase of 0.46 (-0.60, 1.53) in wait-list control (p = 0.017). There were no significant differences in HADS depression, BFI, or ISI scores between yoga and wait-list control. Baseline TES was significantly higher in yoga than in wait-list control (14.9 vs. 12.7, p = 0.019). TES was not associated with HADS anxiety reduction and HADS anxiety reduction was not associated with CIPN pain reduction. CONCLUSIONS: Yoga may reduce anxiety in patients with CIPN. Future studies are needed to confirm these findings. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03292328.

Relationship between peripheral neuropathy and cognitive performance in the elderly population.

ABSTRACT: There are only a few studies that have shown an association of peripheral neuropathy with cognitive impairment in elderly individuals. Therefore, we investigated the relationship between cognitive performance and peripheral neuropathy.From the database of the National Health and Nutrition Examination Survey (NHANES, 1999-2002), each participant completed a household interview, physical performance test, questionnaire regarding personal health, and Digit Symbol Substitution Test (DSST) to evaluate cognitive performance. The severity of peripheral neuropathy was assessed based on the number of insensate areas in both feet during monofilament examination. We used the multivariate linear regression to analyze the association of the DSST findings with insensate areas of the worse foot.There were 828 participants in our study from NHANES 1999 to 2002; their mean age was 69.96 ±â€Š7.38 years, and 51.3% were male. The ß coefficients of the number of insensate areas associated with the DSST findings were all negative values, and the absolute value increased as the number of insensate areas increased. After adjustment for pertinent variables, the correlations remained significantly negative (all P for trend <.001). In addition, subgroup analysis showed no gender differences in the negative association, but this association was not significant in obese participants (P > .05).Our study provides evidence that the severity of peripheral neuropathy is significantly negatively correlated with cognitive performance.

Behavior and electrophysiology studies of the peripheral neuropathy induced by individual and co-administration of paclitaxel and oxaliplatin in rat.

AIMS: Antitumor agents, as taxanes and platinum compounds, induce peripheral neuropathies which can hamper their use for cancer treatment. The study of chemotherapy-induced neuropathies in humans is difficult because of ethical reasons, differences among administration protocols and intrinsic characteristics of patients. The aim of the present study is to compare the neuropathic signs induced by individual or combined administration of paclitaxel and oxaliplatin. MAIN METHODS: Oxaliplatin and paclitaxel were administered individually and combined to induce peripheral neuropathy in rats, sensory neuropathic signs were assessed in the hind limbs and orofacial area. The in vitro skin-saphenous nerve preparation was used to record the axonal activity of Aδ sensory neurons. KEY FINDINGS: Animals treated with the combination developed mechanical allodynia in the paws and muscular hyperalgesia in the orofacial area, which was similar to that in animals treated with monotherapy, the latter also developed cold allodynia in the paws. Aδ-fibers of the rats treated with the combination were hyperexcited and presented hypersensitivity to pressure stimulation of the innervated skin, also similar to that recorded in the fibers of the animals treated with monotherapy. SIGNIFICANCE: Our work objectively demonstrates that the combination of a platinum compound with a taxane does not worsen the development of sensorial neuropathies in rats, which is an interesting data to take into account when the combination of antitumor drugs is necessary. Co-administration of antitumor drugs is more effective in cancer treatment without increasing the risk of the disabling neuropathic side effects.

Inhibition of TLR4 signaling protects mice from sensory and motor dysfunction in an animal model of autoimmune peripheral neuropathy.

BACKGROUND: While the etiology remains elusive, macrophages and T cells in peripheral nerves are considered as effector cells mediating autoimmune peripheral neuropathy (APN), such as Guillain-Barre syndrome. By recognizing both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) signals, TLRs play a central role in the initiation of both innate and adaptive immune responses. In this study, we aimed to understand the involvement of TLR4 in the pathogenesis of APN and explore the potential of TLR4 as a drug target for therapeutic use. METHODS: APN was induced by a partial ligation on one of the sciatic nerves in B7.2 (L31) transgenic mice which possess a predisposed inflammatory background. APN pathology and neurological function were evaluated on the other non-injured sciatic nerve. RESULTS: TLR4 and its endogenous ligand HMGB1 were highly expressed in L31 mice, in circulating immune cells and in peripheral nerves. Enhanced TLR4 signaling was blocked with TAK 242, a selective TLR4 inhibitor, before and after disease onset. Intraperitoneal administration of TAK 242 not only inhibited monocyte, macrophage and CD8+ T cell activation, but also reduced the release of pro-inflammatory cytokines. TAK 242 protected mice from severe myelin and axonal loss, resulting in a remarkable improvement in mouse motor and sensory functions. TAK 242 was effective in alleviating the disease in both preventive and reversal paradigms. CONCLUSION: The study identified the critical contribution of TLR4-mediated macrophage activation in disease course and provided strong evidence to support TLR4 as a useful drug target for treating inflammatory autoimmune neuropathy.

From 'molecules of life' to new therapeutic approaches, an evolution marked by the advent of artificial intelligence: the cases of chronic pain and neuropathic disorders.

The large families of the molecules of life are at the origin of the discovery of new compounds with which to treat disease. The arrival of artificial intelligence (AI) has considerably modified the search for innovative bioactive drugs and their therapeutic applications. Conventional approaches at different organizational research levels have emerged and, thus, AI associated with gene and cell therapies could supplant conventional pharmacotherapy and facilitate the diagnosis of pathologies. Using the examples of chronic pain and neuropathic disorders, which affect a large number of patients, I illustrate here how AI could generate new therapeutic approaches, why some compounds are seen as recreational drugs and others as medicinal drugs, and why, in some countries, psychedelic drugs are considered as potential therapeutic drugs but not in others.

Effects of Chemotherapy-Induced Peripheral Neuropathy in Women With Breast Cancer: A Structural Equation Approach With the Theory of Unpleasant Symptoms.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurotoxic effect. Chemotherapy-induced peripheral neuropathy symptoms have multidimensional characteristics that are associated with various physiologic, psychological, and situational factors and affect individual's abilities to effectively function in performing daily tasks. The theory of unpleasant symptoms mediates the relationships among CIPN symptom experience, reduced performance in daily tasks, and causative factors. OBJECTIVES: The aim of this study was to examine how influencing factors (physiologic, psychological, and situational) affect CIPN symptoms and the impact of symptom experience on functional interference in daily activities of chemotherapy-treated breast cancer survivors. METHODS: A cross-sectional survey about causative factors, CIPN symptoms, and functional interference was completed by 190 women treated with adjuvant chemotherapy for nonmetastatic breast cancer. The hypothetical model was tested using structural equation modeling analysis. RESULTS: The proposed model provided a good fit to the data. Physiologic and psychological factors accounted for 25.5% of the variance in CIPN symptom experience and explained 37.1% of the variance interfering with functional performance through CIPN symptom experience. CONCLUSION: Disease- and treatment-related physiologic factors and coexisting psychological distress play crucial roles in explaining CIPN symptom experience and daily function in breast cancer survivors. IMPLICATIONS FOR PRACTICE: The findings help healthcare professionals to improve long-term care for breast cancer survivors in terms of education for self-monitoring, coping, and establishing supportive environment that can contribute to reducing the unmet needs and interference associated with persistent CIPN.

Diabetes distress and peripheral neuropathy are associated with medication non-adherence in individuals with type 2 diabetes in primary care.

BACKGROUND: Psychosocial factors like diabetes distress and social support, as well as the presence of complications, affect an individual's self-management ability; however, their role in adherence behaviours is not yet clear. We examined the role of psychosocial factors and complications in non-adherence behaviours in individuals with diabetes in primary care. METHODS: Baseline survey with nine-month follow up through medical records of patients with type 2 diabetes attending primary care. Medication adherence and diabetes distress were assessed using Morisky Green Levine Medication Adherence Scale and Problem Areas in Diabetes, respectively. Appointment adherence was assessed through medical records. RESULTS: Of the 448 participants studied, 59.8% had medication non-adherence and 21.7% were non-adherent to scheduled appointments. PAID score (odds ratio (OR) 1.01, 95% confidence interval 1.00-1.03, p = 0.013), peripheral neuropathy (OR 1.99, 95%CI 1.18-3.37, p = 0.01), home glucose monitoring (OR 0.46, 95%CI 0.30-0.69, p < 0.001), HbA1c (OR 1.34, 95%CI 1.13-1.61, p = 0.001), and age (OR 0.96, 95%CI 0.93-0.98, p = 0.001) were associated with medication non-adherence. Indian ethnicity (OR 2.93, 95%CI 1.59-5.39, p = 0.001), secondary or higher education (OR 1.94, 95%CI 1.14-3.27, p = 0.014), and HbA1c (OR 1.38, 95%CI 1.18-1.63, p < 0.001) were associated with appointment non-adherence. CONCLUSIONS: Non-adherence behaviours were prevalent and significantly associated with higher HbA1c. Medication non-adherence was more likely in younger individuals, those with higher diabetes distress or peripheral neuropathy. Appointment non-adherence was more likely in individuals of Indian ethnicity or those with higher education. Greater support for these groups may help improve adherence behaviours and outcomes.

Lagged Relationships Among Chemotherapy-Induced Peripheral Neuropathy, Sleep Quality, and Physical Activity During and After Chemotherapy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is well-documented and can become chronic for up to a third of patients. CIPN management is hampered by limited pharmacological options. Thus, identifying modifiable behaviors that influence CIPN may help inform future interventions. PURPOSE: The purpose of the current study was to examine bidirectional relationships between sleep quality, physical activity, and CIPN during and after chemotherapy. METHODS: Participants were 138 women with gynecologic cancer (M age = 61, 94% white, 96% non-Hispanic), collected as part of an ongoing study. Assessments occurred at postcycle 1, postcycle 6, and 6- and 12-month postchemotherapy. CIPN (EORTC-CIPN20), sleep quality (PSQI), and physical activity (IPAQ) were assessed via self-report. Objective physical activity was assessed via wrist actigraphy. Latent change score models were used to examine lagged relationships between CIPN, sleep quality, and physical activity pairs. RESULTS: Over the study period, sleep quality was found to contribute to CIPN (p = .001), but not the reverse (p > .05). Bidirectional relationships were observed between CIPN and both objective and subjective walking (ps ≤ .001). Illustrations of these relationships showed that patients with less CIPN early in treatment demonstrate more substantial increases in walking over time, while those with higher CIPN demonstrate more consistent levels of walking during and after treatment. CONCLUSIONS: These findings suggest that worse sleep quality and lower walking levels may contribute to the course and maintenance of CIPN. Future investigation should evaluate the impact of early interventions aimed at improving sleep quality and encouraging physical activity in patients treated with chemotherapy.

Lysophospholipids Contribute to Oxaliplatin-Induced Acute Peripheral Pain.

Oxaliplatin, a platinum-based chemotherapeutic drug, which is used as first-line treatment for some types of colorectal carcinoma, causes peripheral neuropathic pain in patients. In addition, an acute peripheral pain syndrome develop in almost 90% of patients immediately after oxaliplatin treatment, which is poorly understood mechanistically but correlates with incidence and severity of the later-occurring neuropathy. Here we investigated the effects of acute oxaliplatin treatment in a murine model, showing that male and female mice develop mechanical hypersensitivity 24 h after oxaliplatin treatment. Interestingly, we found that the levels of several lipids were significantly altered in nervous tissue during oxaliplatin-induced acute pain. Specifically, the linoleic acid metabolite 9,10-EpOME (epoxide of linoleic acid) as well as the lysophospholipids lysophosphatidylcholine (LPC) 18:1 and LPC 16:0 were significantly increased 24 h after oxaliplatin treatment in sciatic nerve, DRGs, or spinal cord tissue as revealed by untargeted and targeted lipidomics. In contrast, inflammatory markers including cytokines and chemokines, ROS markers, and growth factors are unchanged in the respective nervous system tissues. Importantly, LPC 18:1 and LPC 16:0 can induce Ca2+ transients in primary sensory neurons, and we identify LPC 18:1 as a previously unknown endogenous activator of the ligand-gated calcium channels transient receptor potential V1 and M8 (transient receptor potential vanilloid 1 and transient receptor potential melastatin 8) in primary sensory neurons using both pharmacological inhibition and genetic knockout. Additionally, a peripheral LPC 18:1 injection was sufficient to induce mechanical hypersensitivity in naive mice. Hence, targeting signaling lipid pathways may ameliorate oxaliplatin-induced acute peripheral pain and the subsequent long-lasting neuropathy.SIGNIFICANCE STATEMENT The first-line cytostatic drug oxaliplatin can cause acute peripheral pain and chronic neuropathic pain. The former is causally connected with the chronic neuropathic pain, but its mechanisms are poorly understood. Here, we performed a broad unbiased analysis of cytokines, chemokines, growth factors, and ∼200 lipids in nervous system tissues 24 h after oxaliplatin treatment, which revealed a crucial role of lysophospholipids lysophosphatidylcholine (LPC) 18:1, LPC 16:0, and 9,10-EpOME in oxaliplatin-induced acute pain. We demonstrate for the first time that LPC 18:1 contributes to the activation of the ion channels transient receptor potential vanilloid 1 and transient receptor potential melastatin 8 in sensory neurons and causes mechanical hypersensitivity after peripheral injection in vivo These findings suggest that the LPC-mediated lipid signaling is involved in oxaliplatin-induced acute peripheral pain.

Peripheral neuropathic pain.

Neuropathic pain (NP) can have either central nervous system causes or ones from the peripheral nervous system. This article will focus on the epidemiology, classifications, pathology, non-invasive treatments and invasive treatments as a general review of NP involving the peripheral nervous system. NP has characteristic symptomatology such as burning and electrical sensations. It occurs in up to 10% of the general population. Its frequency can be attributed to its occurrence in neck and back pain, diabetes and patients receiving chemotherapy. There are a wide range of pharmacologic options to control this type of pain and when such measures fail, numerous interventional methods can be employed such as nerve blocks and implanted stimulators. NP has a cost to the patient and society in terms of emotional consequences, quality of life, lost wages and the cost of assistance from the medical system and thus deserves serious consideration for prevention, treatment and control.

The relevance of multimodal assessment in experimental oxaliplatin-induced peripheral neurotoxicity.

Chemotherapy-induced peripheral neurotoxicity represents one of the most relevant dose-limiting side effects that can affect cancer patients treated with the common antineoplastic agents. Since the severity of neurotoxicity often leads to dose reduction or early cessation of chemotherapy, the investigation of molecular mechanisms underlying chemotherapy-induced peripheral neurotoxicity is an urgent clinical need in order to better understand its physiopathology and find effective strategies for neuroprotection. Several in vivo preclinical models of chemotherapy-induced peripheral neurotoxicity have been developed but a great variability in mouse strain, dose, route of administration of the drug, treatment schedule and assessment of neurotoxicity is observed between the different published studies making difficult the comparison and interpretation of their results. In many of these studies only behavioural tests are used as outcome measures, while possible neurophysiological and neuropathological changes are not evaluated. In this study, focused on experimental oxaliplatin-induced peripheral neurotoxicity, we reproduced and compared four mouse models with very different drug dose (low or high dose-intensity) and treatment schedules (short or long-term treatment), selected from the literature. Using a multimodal assessment based on behavioural, neurophysiological and neuropathological methods, we evidenced remarkable differences in the results obtained in the selected animal models. This work suggests the importance of a multimodal approach including extensive pathological investigation to confirm the behavioural results.

Peripheral neuropathy and depressive symptoms: examining the association in a primary health care setting among persons with and without diabetes mellitus.

PURPOSE: The purpose of this study was to measure the association between peripheral neuropathy symptoms and depressive symptoms among a sample of patients with and without diabetes mellitus (DM). METHODS: Patients were administered the 15-item Michigan Neuropathy Screening Instrument (MNSI) and the patient health questionnaire depression scale (PHQ-8). Patients with an MNSI score ≥ 4 were categorized as having PN and patients with a PHQ-8 score ≥ 10 were considered to have current depression. Log-binomial regression was used to analyze the relationship between PN and depressive symptoms. RESULTS: 406 patients were included in the final analysis. There were no statistically significant differences by diabetes status in PN symptoms (Diabetes = 61.8%; No diabetes = 55.4%; p = .20) or in depression status (Diabetes = 37.6%; No diabetes = 36.6%; p = .83). After adjustment for covariates, PN was associated with depression (aRR = 4.46; 95% CI 2.91,6.85) independent of diabetes status. CONCLUSIONS: PN symptoms may be common among aging persons even in the absence of DM. Past literature and our study demonstrate that PN and depression are closely associated. More work is needed to understand the etiology and potential utility of intervention for depression symptoms among patients with neuropathy.

Psychometric testing of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) subscale in a longitudinal study of cancer patients treated with chemotherapy.

BACKGROUND: The aim of this study was to evaluate the psychometric properties of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) subscale in a longitudinal study of cancer patients treated with chemotherapy. METHODS: Patients were assessed with the FACT/GOG-Ntx subscale, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy Scale 20 (EORTC QLQ-CIPN20), National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE), and light touch test using 10 g monofilament for up to ten assessment points from baseline (prior to initiation of first chemotherapy), after the end of each cycle (up to 6 cycles, 3 weeks per cycle), and at 6, 9, and 12 months after starting chemotherapy. Psychometric analyses included internal consistency reliability, convergent validity, factorial validity, sensitivity to change and responsiveness (minimal clinically important difference, MCID). RESULTS: Cronbach's alpha coefficients of the FACT/GOG-Ntx subscale were 0.82-0.89 across assessment points. The subscale strongly correlated with the EORTC QLQ-CIPN20 (r = 0.79-0.93) but low-to-moderately correlated with the NCI-CTCAE sensory (rs = 0.23-0.45) and motor items (rs = 0.15-0.50) as well as the monofilament test (rs = 0.23-0.47). The hypothesized 4-factor structure of the FACT/GOG-Ntx subscale was not confirmed at assessment points (χ2/df = 2.26-8.50; all P < 0.001). The subscale exhibited small-to-moderate sensitivity to change (r = 0.17-0.37). The MCIDs were between 1.38 and 3.68. CONCLUSION: The FACT/GOG-Ntx subscale has satisfactory reliability, validity, sensitivity to change and responsiveness to evaluate CIPN in cancer patients. Future research is needed to explore the factorial structure of the FACT/GOG-Ntx subscale as the published four-factor structure was not supported in this study.

The associations between physical activity, neuropathy symptoms and health-related quality of life among gynecologic cancer survivors.

OBJECTIVE: Physical activity may mitigate the effects of cancer treatment. We sought to evaluate the association between self-reported physical activity, neuropathy symptomatology, and emotional health in gynecologic cancer survivors. METHODS: Patients were recruited from an academic gynecologic oncology practice to a prospective cohort study. Participants completed semiannual surveys on quality of life (QOL), neuropathy symptoms, depression, distress, and health behaviors. Abstracted clinical data included cancer type, FIGO stage at diagnosis and treatments received (chemotherapy, surgery, radiation). Physical activity [no: moderate physical activity <150 min/week, yes: ≥150 min/week] and neuropathy symptomatology [high (FACT/GOG-Ntx ≥11; upper quartile); low (<11)] were dichotomized. Linear regression models assessed the associations between physical activity, neuropathy and psychosocial outcomes. RESULTS: A total of 194 participants were included in this analysis. We identified significant interactions between physical activity and neuropathy in the depression (p = 0.0006) and QOL (p = 0.007) models. Greater physical activity and lower neuropathy scores were independently associated with fewer depressive symptoms (p = 0.02 and p < 0.0001, respectively) and greater QOL (p = 0.005 and p < 0.0001). Low neuropathy scores were associated with lower distress (p < 0.0001). Women with high neuropathy scores had larger beneficial associations between being physically active and depression and QOL. In the distress model, interaction between neuropathy and physical activity was suggested (p = 0.05). CONCLUSIONS: Physical activity was associated with favorable psychosocial outcomes in gynecologic cancer survivors, most notably among those with worse neuropathy. These data suggest prescriptive exercise should be evaluated as a means of mitigating cancer-associated neuropathies and their effect on emotional health.

Vortioxetine reduces pain hypersensitivity and associated depression-like behavior in mice with oxaliplatin-induced neuropathy.

Chronic pain and depression commonly occur together so dual-acting agents might be particularly useful. The population of patients with chemotherapy-induced neuropathy is increasing in parallel with the increase of population of cancer survivors and there is a compelling need for satisfactory treatment of symptoms of neuropathy and concomitant depression. We examined the effects of vortioxetine, a novel antidepressant with unique mechanism of action, on pain hypersensitivity and depression-like behavior in oxaliplatin-induced neuropathy model in mice (OIPN). Vortioxetine (1-10 mg/kg, p.o.) significantly and dose-dependently reduced mechanical allodynia in von Frey test and cold allodynia in acetone test in OIPN mice, in both repeated prophylactic and acute therapeutic treatment regimens. It also reduced depression-like behavior in the forced swimming test in OIPN mice, in both treatment paradigms. Its antiallodynic and antidepressive-like effects were comparable to those exerted by duloxetine (1-15 mg/kg, p.o.). The antiallodynic and antidepressive-like effects of repeatedly administered vortioxetine might be related to the increased content of 5-hydroxytryptamine (5-HT) and noradrenaline (NA), detected in the brainstem of treated OIPN mice. These results indicate that vortioxetine could be potentially useful in prevention and treatment of chemotherapy-induced neuropathy, for the relief of pain and concomitant depressive symptoms. It should be further tested to this regard in clinical settings.

The Physical Consequences of Chemotherapy-Induced Peripheral Neuropathy.

PURPOSE OF REVIEW: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of numerous chemotherapy drugs. CIPN negatively impacts function and quality of life during and after treatment. We will provide a review of the data describing the physical consequences of CIPN and discuss the possible long term impact on emotional well-being and quality of life. RECENT FINDINGS: CIPN negatively affects physical function and many aspects of quality of life. Exercise interventions are likely to reduce the risk of falls associated with CIPN. There remains a need for evidence-based interventions focused on improving symptoms, function, and quality of life in persons with CIPN.