Cancer health self-efficacy improvement in a randomized controlled trial.

BACKGROUND: eHealth interventions can help cancer survivors self-manage their health outside the clinic. Little is known about how best to engage and assist survivors across the age and cancer treatment spectra. METHODS: The American Cancer Society conducted a randomized controlled trial that assessed efficacy of, and engagement with, Springboard Beyond Cancer, an eHealth self-management program for cancer survivors. Intent-to treat analyses assessed effects of intervention engagement for treatment (on-treatment vs completed) overall (n = 176; 88 control, 88 intervention arm) and separately by age (<60 years vs older). Multiple imputation was used to account for participants who were lost to follow-up (n = 41) or missing self-efficacy data (n = 1) at 3 months follow-up. RESULTS: Self-efficacy for managing cancer, the primary outcome of this trial, increased significantly within the intervention arm and for those who had completed treatment (Cohen's d = 0.26, 0.31, respectively). Additionally, participants with moderate-to-high engagement in the text and/or web intervention (n = 30) had a significantly greater self-efficacy for managing cancer-related issues compared to the control group (n = 68), with a medium effect size (Cohen's d = 0.44). Self-efficacy did not differ between the intervention and control arm at 3 months post-baseline. CONCLUSIONS: Study results suggest that cancer survivors benefit variably from eHealth tools. To maximize effects of such tools, it is imperative to tailor information to a priori identified survivor subgroups and increase engagement efforts.

A user centered design approach to development of an online self-management program for cancer survivors: Springboard Beyond Cancer.

OBJECTIVE: The American Cancer Society and the National Cancer Institute launched and evaluated a personalized online program leveraging behavioral science principles to help people self-manage physical and emotional symptoms, improve communication skills, and lead healthier lives during and after a cancer diagnosis. METHODS: Cancer survivors were recruited from an academic medical and a community clinical setting (N = 40) to complete in-person user testing of the Springboard Beyond Cancer website, which included action decks and content to promote self-management. Action decks were printable or savable collections of information and action steps related to a cancer topic or treatment side effect. Participants performed structured tasks to evaluate the program's content and usability. Comments and reactions were recorded, and qualitative thematic analyses were conducted. RESULTS: Most participants successfully found information about fatigue (95%), pain (83%), sexual side effects (90%), and support groups (85%). Survivors, particularly those in treatment, found information on the site to be clear, concise, and meeting their needs. Use of action decks to create self-management plans was inconsistent. Survivors reported needing more instruction and support within the program on how to best utilize enhanced functionality in action decks to prioritize their most pressing concerns. CONCLUSIONS: Early stakeholder engagement throughout the multiple phases of prototyping and deployment are needed to fully maximize end user engagement. Providing actionable self-management content and activating tools to cancer survivors via an eHealth program is a feasible and scalable approach to increasing access to self-management tools and addressing cancer survivor needs.

Disentangling Efficacy and Expectations: A Prospective, Cross-lagged Panel Study of Cancer Survivors' Physical Activity.

Background: Despite demonstrated utility of Bandura's social cognitive theory for increasing physical activity among cancer survivors, the validity of the originally hypothesized relationships among self-efficacy, outcome expectations, and physical activity behavior continues to be debated. Purpose: To explore the temporal ordering of outcome expectations and self-efficacy as they relate to moderate-to-vigorous physical activity behavior. Methods: Longitudinal data from cancer survivors (N = 1,009) recently completing treatment were used to fit six cross-lagged panel models, including one parent model, one model representing originally hypothesized variable relationships, and four alternative models. All models contained covariates and used full information maximum likelihood and weighted least squares mean and variance adjusted estimation. Tests of equal fit between the parent model and alternative models were conducted. Results: The model depicting Bandura's originally hypothesized relationships showed no statistically significant relationship between outcome expectations and physical activity (p = .18), and was a worse fit to the data, compared with the parent model [Χ2 (1) = 5.92, p = .01]. An alternative model showed evidence of a reciprocal relationship between self-efficacy and outcome expectations, and was statistically equivalent to the parent model [Χ2(1) = 2.01, p = .16]. Conclusions: This study provides evidence against Bandura's theoretical assertions that (a) self-efficacy causes outcome expectations and not vice versa, and (b) outcome expectation has a direct effect on physical activity. Replication within population subgroups and for other health behaviors will determine whether the social cognitive theory needs modification. Future trials should test whether differential construct ordering results in clinically meaningful differences in physical activity behavior change.

Reduced Prevalence of Obesity in 14 Disadvantaged Black Communities in the United States: A Successful 4-Year Place-Based Participatory Intervention.

OBJECTIVES: To assess the impact of a large-scale place-based intervention on obesity prevalence in Black communities. METHODS: The Racial and Ethnic Approaches to Community Health across the United States (REACH US) project was conducted in 14 predominantly Black communities in California, Illinois, Massachusetts, New York, Ohio, Pennsylvania, South Carolina, Virginia, Washington, and West Virginia. We measured trends from 2009 to 2012 in the prevalence of obesity. We used Behavioral Risk Factor Surveillance System data to compare these trends with trends among non-Hispanic Whites and non-Hispanic Blacks in the United States and in the 10 states where REACH communities were located, and with a propensity score-matched national sample of non-Hispanic Blacks. RESULTS: The age-standardized prevalence of obesity decreased in REACH US communities (P = .045), but not in the comparison populations (P = .435 to P = .996). The relative change was -5.3% in REACH US communities versus +2.4% in propensity score-matched controls (P value for the difference = .031). The net effect on the reduction of obesity prevalence was about 1 percentage point per year for REACH. CONCLUSIONS: Obesity prevalence was reduced in 14 disadvantaged Black communities that participated in the REACH project.

Relationship between child care centers' compliance with physical activity regulations and children's physical activity, New York City, 2010.

INTRODUCTION: Physical activity may protect against overweight and obesity among preschoolers, and the policies and characteristics of group child care centers influence the physical activity levels of children who attend them. We examined whether children in New York City group child care centers that are compliant with the city's regulations on child physical activity engage in more activity than children in centers who do not comply. METHODS: A sample of 1,352 children (mean age, 3.39 years) served by 110 group child care centers in low-income neighborhoods participated. Children's anthropometric data were collected and accelerometers were used to measure duration and intensity of physical activity. Multilevel generalized linear regression modeling techniques were used to assess the effect of center- and child-level factors on child-level physical activity. RESULTS: Centers' compliance with the regulation of obtaining at least 60 minutes of total physical activity per day was positively associated with children's levels of moderate to vigorous physical activity (MVPA); compliance with the regulation of obtaining at least 30 minutes of structured activity was not associated with increased levels of MVPA. Children in centers with a dedicated outdoor play space available also spent more time in MVPA. Boys spent more time in MVPA than girls, and non-Hispanic black children spent more time in MVPA than Hispanic children. CONCLUSION: To increase children's level of MVPA in child care, both time and type of activity should be considered. Further examination of the role of play space availability and its effect on opportunities for engaging in physical activity is needed.

Evaluation design of New York City's regulations on nutrition, physical activity, and screen time in early child care centers.

This article describes the multi-method cross-sectional design used to evaluate New York City Department of Health and Mental Hygiene's regulations of nutrition, physical activity, and screen time for children aged 3 years or older in licensed group child care centers. The Center Evaluation Component collected data from a stratified random sample of 176 licensed group child care centers in New York City. Compliance with the regulations was measured through a review of center records, a facility inventory, and interviews of center directors, lead teachers, and food service staff. The Classroom Evaluation Component included an observational and biometric study of a sample of approximately 1,400 children aged 3 or 4 years attending 110 child care centers and was designed to complement the center component at the classroom and child level. The study methodology detailed in this paper may aid researchers in designing policy evaluation studies that can inform other jurisdictions considering similar policies.

Measurement of compliance with New York City's regulations on beverages, physical activity, and screen time in early child care centers.

INTRODUCTION: Policy interventions designed to change the nutrition environment and increase physical activity in child care centers are becoming more common, but an understanding of the implementation of these interventions is yet to be developed. The objective of this study was to explore the extent and consistency of compliance with a policy intervention designed to promote nutrition and physical activity among licensed child care centers in New York City. METHODS: We used a multimethod cross-sectional approach and 2 independent components of data collection (Center Evaluation Component and Classroom Evaluation Component). The methods were designed to evaluate the impact of regulations on beverages served, physical activity, and screen time at child care centers. We calculated compliance scores for each evaluation component and each regulation and percentage agreement between compliance in the center and classroom components. RESULTS: Compliance with certain requirements of the beverage regulations was high and fairly consistent between components, whereas compliance with the physical activity regulation varied according to the data collection component. Compliance with the regulation on amount and content of screen time was high and consistent. CONCLUSION: Compliance with the physical activity regulation may be a more fluid, day-to-day issue, whereas compliance with the regulations on beverages and television viewing may be easier to control at the center level. Multiple indicators over multiple time points may provide a more complete picture of compliance - especially in the assessment of compliance with physical activity policies.

Afraid and tired: A longitudinal study of the relationship between cancer-related fatigue and fear of cancer recurrence in long-term cancer survivors.

OBJECTIVE: Cancer-related fatigue (CRF) and fear of cancer recurrence (FCR) are two common concerns experienced by cancer survivors. However, the relationship between these two concerns is poorly understood, and whether CRF and FCR influence each other over time is unclear. METHODS: Data were from a national, prospective, longitudinal study, the American Cancer Society's Study of Cancer Survivors-I (SCS-I). Surveys were completed by 1395 survivors of 10 different cancer types at three time-points, including assessment 1.3 years (T1), 2.2 years (T2) and 8.8 years (T3) following their cancer diagnosis. CRF was assessed using the fatigue-inertia subscale of the Profile of Mood States, and FCR by the FCR subscale of the Cancer Problems in Living Scale. Multiple group random intercepts cross-lagged panel models investigated prospective associations between CRF and FCR. RESULTS: For younger participants (at or below median age of 55 years, n = 697), CRF at T1 and T2 marginally and significantly predicted FCR at T2 and T3, respectively, but no lagged effects of FCR on subsequent CRF were observed. Cross-lagged effects were not observed for survivors over 55 years of age. CONCLUSION: Both CRF and FCR are debilitating side effects of cancer and its treatments. Given that CRF may be predictive of FCR, it possible that early detection and intervention for CRF could contribute to lowering FCR severity.

PKCγ receptor mediates visceral nociception and hyperalgesia following exposure to PTSD-like stress in the spinal cord of rats.

BACKGROUND: Clinical studies indicate that patients with post-traumatic stress disorder (PTSD) frequently share comorbidity with numerous chronic pain conditions. However, the sustained effects of PTSD-like stress over time on visceral nociception and hyperalgesia have been rarely studied, and the underlying mechanisms of stress-induced modulation of visceral hyperalgesia remain elusive. The purpose of this study was to investigate the characterization of visceral nociception and hyperalgesia over time in rats exposed to PTSD-like stress, and to explore the potential role of protein kinase C gamma (PKCγ) in mediating visceral hyperalgesia following exposure to PTSD-like stress. RESULTS: On day 1, the rats exposed to single-prolonged stress (SPS, an established animal model for PTSD) exhibited an analgesic response and its visceromotor response (VMR) to graded colorectal distention (CRD) at 40 and 60 mmHg was reduced compared with the control group (all P < 0.05). On day 6, the VMR returned to the baseline value. However, as early as 7 days after SPS, VMR dramatically increased compared with its baseline value and that in the controls (all P < 0.001) and this increase persisted for 28 days, with the peak on day 9. Abdominal withdrawal reflex (AWR) scores were higher in SPS rats than in controls on days 7, 9, 14, 21 and 28 (all P < 0.001). Intrathecal administration of GF109203X (an inhibitor of PKC gamma), attenuated the SPS-induced increase in both VMR and AWR scores on days 7, 14, 21 and 28 (all P < 0.05). PKCγ protein expression determined by immunofluorescence was reduced in the spinal cord within 3 days after the exposure to SPS (P < 0.01), which returned to normal levels between days 4 and 6, and significantly increased from day 7, and this increase was maintained on days 14, 21, and 28 (all P < 0.001), with the peak on day 9. In addition, Western blotting showed a consistent trend in the changes of PKCγ protein expression. CONCLUSIONS: The modified SPS alters visceral sensitivity to CRD, and contributes to the maintenance of visceral hyperalgesia, which is associated with enhanced PKCγ expression in the spinal cord. Functional blockade of the PKCγ receptors attenuates SPS-induced visceral hyperalgesia. Thus, the present study identifies a specific molecular mechanism for visceral hyperalgesia which may pave the way for novel therapeutic strategies for PTSD-like conditions.

Longitudinal analysis of peer social support and quitting Smoking: Moderation by sex and implications for cessation interventions.

Social support predicts better health and lower mortality, but the benefits of peer social support for helping cigarette smokers quit are unclear. Moreover, sex as a moderating factor has not been investigated despite sex differences in social support processes. This study of smokers' perceived availability of peer social support in quitting cigarette smoking is a secondary analysis of 1,010 individuals enrolled in an RCT that provided quitting assistance using tailored emails scheduled around a quit date. Participants completed measures of peer support for quitting cigarettes at enrollment (baseline), and at 1-, 3-, and 6-month follow-ups. Peer support at follow-ups was categorized as never-present, always-present, or mixed. A Generalized Estimating Equation (GEE) examined the association between peer support and 7-day point prevalence abstinence at follow-ups, controlling for baseline peer support, experimental condition, stress, depression, and sociodemographic and smoking behavior-related variables. Interactions of peer support × time, and peer support × sex, were tested. Results indicated that among women, always-present or mixed peer support was associated with, respectively, odds of abstinence that were 4.36 (95 % CI, 2.54-7.49, p = 0.0001), and 2.21 (OR = 2.21, 95 % CI, 1.27-3.85, p = 0.005) greater than among women reporting never-present peer support. Among men, peer support did not predict abstinence. Women who smoke may be especially receptive to the benefits of peer support when attempting to quit. Investigation of the basis of their perceptions, how they might be increased, and whether interventions to change them would be effective, is warranted.

Testing the effects of a decision aid for prostate cancer screening.

There is an ever-growing trend toward more patient involvement in making health care decisions. This trend has been accompanied by the development of "informed decision-making" interventions to help patients become more engaged and comfortable with making these decisions. We describe the effects of a prostate cancer screening decision aid on knowledge, beliefs about screening, risk perception, control preferences, decisional conflict, and decisional anxiety. Data were collected from 200 males aged 50-70 years in the general population who randomly were assigned to exposure to the decision aid or no exposure as a control condition. A Solomon four-group design was used to test for possible pretest sensitization effects and to assess the effects of exposure to the decision aid. No significant pretest sensitization effects were found. Analysis of the exposure effects found that knowledge increased significantly for those exposed to the decision aid compared with those unexposed. Exposure to the decision aid also had some influence on decreasing both decisional conflict and decisional anxiety. Decision aids can play an important role in increasing patients' knowledge and decreasing anxiety when asked to make health care decisions.

Substance use patterns and mental health diagnosis among youth in mental health treatment: a latent class analysis.

This study examines patterns of substance use among youth served in systems of care, and how these patterns relate to diagnosis and other youth characteristics using latent class analysis. Results indicated a four-class solution with the four groups differing in their probabilities of reporting the use of 10 different substances. Class 1 was defined by high probabilities of all drug use. Class 2 had high probabilities of alcohol, tobacco, marijuana use, and low for other drugs. Class 3 had moderate probabilities of alcohol, tobacco, marijuana use, and low probabilities for other drugs. Class 4 had a high probability of tobacco use and no other drug use. Youth who had a mood disorder diagnosis, were male, older, White and had previously run away from home were significantly more likely to be in Class 1 relative to other classes. These differences have implications for prevention and treatment.

Influence of a patient decision aid on decisional conflict related to PSA testing: a structural equation model.

OBJECTIVE: To examine the impact of a decision aid (DA) designed to promote informed decision making for screening with the prostate-specific antigen (PSA) test and to test a theoretical model of factors influencing decisional conflict. DESIGN: Structural equation modeling examined pathways between DA exposure, knowledge, schema, prostate cancer risk perceptions, decisional anxiety, and decisional conflict. Sample participants included 200 men from the general population (exclusive of African Americans) and 200 African American men. Half of the men in each subsample were randomly assigned to receive the DA. MAIN OUTCOME MEASURES: Decisional conflict regarding prostate cancer screening. RESULTS: The DA influences level of decisional conflict by increasing patient knowledge. This effect of knowledge on decisional conflict is indirect, however, through an association with greater perceived risk and lower decisional anxiety. Also, positive PSA schema was associated with lower decisional anxiety and decisional conflict. It is important that exposure to the DA had no impact on PSA schema. CONCLUSION: Schemas about testing must be considered in developing messages about the risks and benefits of testing. If schemas are counter to message content, mechanisms for modifying schemas must be incorporated into interventions.

Evaluation of Colorectal Cancer Screening in Federally Qualified Health Centers.

INTRODUCTION: Screening for colorectal cancer in average-risk adults is recommended beginning at age 50 years and continuing until age 75 years. This study was conducted to provide evidence for the effectiveness of an American Cancer Society grant program promoting colorectal cancer screening by implementing evidence-based interventions proven to increase screening rates. METHODS: Analysis compared colorectal cancer screening rates in 77 grant-funded federally qualified health centers between 2013 and 2015 to those of a sample of 77 nonfunded federally qualified health centers selected using a genetic matching technique. The Uniform Data System from 2013 to 2015 provided data used in the analysis performed in 2016. RESULTS: Funded grantees differed significantly from nongrantees on several indicators at baseline. Genetic matching resulted in good-quality matched samples. Both matched samples increased colorectal cancer screening rates over time. Grantees increased their colorectal cancer screening rates significantly more than nongrantees, especially between 2013 and 2014, where funded federally qualified health centers increased by 9% and nonfunded federally qualified health centers increased by 3%. Across the 3 years, increases were 12% and 9%, respectively. CONCLUSIONS: The findings suggest grant funding was effective in promoting improvements in colorectal cancer screening rates in funded federally qualified health centers, and these improvements exceed those of nonfunded federally qualified health centers. Funding that results in targeted, intensive efforts supported by technical assistance and accountability for data and reporting, can result in improved system policies and practices that, in turn, can increase screening rates among uninsured and underserved populations.

Predicting Positive Education Outcomes for Emerging Adults in Mental Health Systems of Care.

Emerging adults who receive services based on positive youth development models have shown an ability to shape their own life course to achieve positive goals. This paper reports secondary data analysis from the Longitudinal Child and Family Outcome Study including 248 culturally diverse youth ages 17 through 22 receiving mental health services in systems of care. After 12 months of services, school performance was positively related to youth ratings of school functioning and service participation and satisfaction. Regression analysis revealed ratings of young peoples' perceptions of school functioning, and their experience in services added to the significant prediction of satisfactory school performance, even controlling for sex and attendance. Finally, in addition to expected predictors, participation in planning their own services significantly predicted enrollment in higher education for those who finished high school. Findings suggest that programs and practices based on positive youth development approaches can improve educational outcomes for emerging adults.

Role of spinal cord glutamate transporter during normal sensory transmission and pathological pain states.

Glutamate is a neurotransmitter critical for spinal excitatory synaptic transmission and for generation and maintenance of spinal states of pain hypersensitivity via activation of glutamate receptors. Understanding the regulation of synaptically and non-synaptically released glutamate associated with pathological pain is important in exploring novel molecular mechanisms and developing therapeutic strategies of pathological pain. The glutamate transporter system is the primary mechanism for the inactivation of synaptically released glutamate and the maintenance of glutamate homeostasis. Recent studies demonstrated that spinal glutamate transporter inhibition relieved pathological pain, suggesting that the spinal glutamate transporter might serve as a therapeutic target for treatment of pathological pain. However, the exact function of glutamate transporter in pathological pain is not completely understood. This report will review the evidence for the role of the spinal glutamate transporter during normal sensory transmission and pathological pain conditions and discuss potential mechanisms by which spinal glutamate transporter is involved in pathological pain.

Spinal glutamate uptake is critical for maintaining normal sensory transmission in rat spinal cord.

Glutamate is a major excitatory neurotransmitter in primary afferent terminals and is critical for normal spinal excitatory synaptic transmission. However, little is known about the regulation of synaptically released glutamate in the spinal cord under physiologic conditions. The sodium-dependent, high-affinity glutamate transporters are the primary mechanism for the clearance of synaptically released glutamate. In the present study, we found that intrathecal injection of glutamate transporter blockers DL-threo-beta-benzyloxyaspartate (TBOA) and dihydrokainate produced significant and dose-dependent spontaneous nociceptive behaviors, such as licking, shaking, and caudally directed biting, phenomena similar to the behaviors caused by intrathecal glutamate receptor agonists. Intrathecal TBOA also led to remarkable hypersensitivity in response to thermal and mechanical stimuli. These behavioral responses could be significantly blocked by intrathecal injection of the NMDA receptor antagonists MK-801 and AP-5, the non-NMDA receptor antagonist CNQX or the nitric oxide synthase inhibitor L-NAME. In vivo microdialysis analysis showed short-term elevation of extracellular glutamate concentration in the spinal cord after intrathecal injection of TBOA. Furthermore, topical application of TBOA on the dorsal surface of the spinal cord resulted in a significant elevation of extracellular glutamate concentration demonstrated by in vivo glutamate voltametry. The present study indicates that defective spinal glutamate uptake caused by inhibition of glutamate transporters leads to excessive glutamate accumulation in the spinal cord. The latter results in persistent over-activation of synaptic glutamate receptors, producing spontaneous nociceptive behaviors and sensory hypersensitivity. Our results suggest that glutamate uptake through spinal glutamate transporters is critical for maintaining normal sensory transmission under physiologic conditions.

Anti-fibroblast growth factor-2 antibodies attenuate mechanical allodynia in a rat model of neuropathic pain.

Peripheral nerve injury leads to the activation of spinal cord astrocytes, which contribute to maintaining neuropathic (NP) pain behavior. Fibroblast growth factor-2 (FGF-2), a neurotrophic and gliogenic factor, is upregulated by spinal cord astrocytes in response to ligation of spinal nerves L5 and L6 (spinal nerve ligation [SpNL]). To evaluate the contribution of spinal astroglial FGF-2 to mechanical allodynia following SpNL, neutralizing antibodies to FGF-2 were injected intrathecally. Administration of 18 microg of anti-FGF-2 antibodies attenuated mechanical allodynia at day 21 after SpNL and reduced FGF-2 and glial acidic fibrillary protein mRNA expression and immunoreactivity in the L5 spinal cord segment of rats with SpNL. These results suggest that endogenous astroglial FGF-2 contributes to maintaining NP tactile allodynia associated with reactivity of spinal cord astrocytes and that inhibition of spinal FGF-2 ameliorates NP pain signs.

Glutamate uptake is attenuated in spinal deep dorsal and ventral horn in the rat spinal nerve ligation model.

Alteration of glutamatergic (GLU) neurotransmission within the spinal cord contributes to hyperalgesic and allodynic responses following nerve injury. In particular, changes in expression and efficacy of glutamate transporters have been reported. Excitatory, pain transmitting primary afferent neurons utilizing glutamate as an excitatory neurotransmitter project to both superficial (I-II) and deep (III-V) laminae of the dorsal horn. These experiments were designed to examine changes in glutamate uptake occurring concomitantly within the spinal deep dorsal and ventral horn in situ after experimentally induced neuropathic pain. In vivo voltammetry, using microelectrode arrays configured for enzyme-based detection of GLU were employed. Sprague-Dawley rats had either sham surgery or tight ligation of L5 and L6 spinal nerves (SNL). Four to six weeks later, the L4-L6 spinal cord of chloral hydrate-anesthetized animals was exposed, and ceramic-based glutamate microelectrodes equipped with glass micropipettes 50 microm from the recording surfaces were placed stereotaxically at sites within the spinal cord. Pressure ejection of GLU into the ipsilateral L5-L6 spinal cord resulted in a 72% reduction of GLU uptake in SNL rats compared to sham controls in the ipsilateral L5-L6 deep dorsal horn and a 96% reduction in the ventral horn. In contrast, in the same animals, the contralateral L5-L6 or the ipsilateral L4 spinal cord showed no change in glutamate uptake. The data suggest that spinal nerve ligation produced attenuated glutamate uptake activity extending into the deep dorsal and ventral horn. The study suggests that plasticity related to spinal nerve injury produces widespread alteration in glutamate transporter function that may contribute to the pathophysiology of neuropathic pain.

Reduced basal release of serotonin from the ventrobasal thalamus of the rat in a model of neuropathic pain.

Drugs that inhibit reuptake of monoamines are frequently used to treat pain syndromes, e.g. neuropathy or fibromyalgia, where mechanical allodynia is present. Several lines of evidence suggest the involvement of supraspinal sites of action of these drugs. However, a direct study of supraspinal serotonin (5-HT) or norepinephrine (NE) release in an animal model in which allodynia is expressed, e.g. neuropathy, has not been done. The ventrobasal (VB) thalamus and the hypothalamus are major supraspinal projection regions for spinal neurons that transmit nociceptive information and are innervated by monoaminergic fibers. This study determined if peripheral neuropathy would induce changes in extracellular monoamines in VB thalamus and hypothalamus. Male Sprague-Dawley rats had spinal nerve roots L5 and L6 tightly ligated (neuropathic rats; NP) or sham (SHAM) surgery; contralateral and ipsilateral VB thalamus and contralateral hypothalamus were dialyzed with modified artificial cerebral spinal fluid (aCSF), with and without fluoxetine. NP rats had significantly decreased 5-HT content in dialysates of the contralateral VB thalamus compared with SHAM rats with (82% decrease) or without (63% decrease) fluoxetine in the perfusion medium over the 180 min of the study. There were no differences in the ipsilateral VB thalamus. In contrast, release of 5-HT was unchanged in the hypothalamic dialysates of SHAM vs. NP rats. NE release was not different in dialysates of either the VB thalamus or hypothalamus of SHAM vs. NP rats. Synthesis of 5-HT, as assessed by accumulation of 5-hydroxytrytophan after treatment with an L-amino acid decarboxylase inhibitor, was not different between NP and SHAM rats in VB thalamic and hypothalamic brain tissue. This study is the first to demonstrate changes in monoamine release supraspinally in NP rats. The differential effect between VB thalamus and hypothalamus suggests that a terminal field change may be involved. Putative mechanisms for mediating this change include alterations of GABA-ergic systems and/or plasticity related to alterations in N-methyl-D-aspartate receptor activation and nitric oxide release related to afferent hyperactivity induced by neuropathic pain.