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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.

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Examining the effectiveness of pain rehabilitation on chronic pain and post-traumatic symptoms.

Patients with co-morbid chronic pain and post-traumatic stress disorder (PTSD) pose significant treatment challenges. This study evaluated the effectiveness of an interdisciplinary pain rehabilitation program (IPRP) in improving pain and PTSD outcomes, as well as reducing medication use. In addition, the mediating effect of pain catastrophizing, which is theorized to underlie the pain and PTSD comorbidity, was examined. Participants included 83 completers of an IPRP with chronic pain and a provisional PTSD diagnosis. Significant improvements were found for pain outcomes, PTSD symptomatology, depressive symptoms, physical performance, and medication use (i.e., opioids and benzodiazepines). At discharge, 86.7% of participants reliably improved in at least one key measure of functioning and 50.6% demonstrated reliable improvement in PTSD symptomatology. Change in pain catastrophizing mediated improvements in pain interference and PTSD symptomatology. Results support the potential utility of an interdisciplinary pain treatment approach in the treatment of patients with comorbid pain and PTSD.

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Neuroimmune Interactions in Pain and Stress: An Interdisciplinary Approach.

Mounting evidence indicates that disruptions in bidirectional communication pathways between the central nervous system (CNS) and peripheral immune system underlie the etiology of pathologic pain conditions. The purpose of this review is to focus on the cross-talk between these two systems in mediating nociceptive circuitry under various conditions, including nervous system disorders. Elevated and prolonged proinflammatory signaling in the CNS is argued to play a role in psychiatric illnesses and chronic pain states. Here we review current research on the dynamic interplay between altered nociceptive mechanisms, both peripheral and central, and physiological and behavioral changes associated with CNS disorders.

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Persistent pain and cognitive decline in older adults: a systematic review and meta-analysis from longitudinal studies.

Both persistent pain and cognitive decline prevalence increase with advancing age and are associated with functional decline. However, the association of pain and cognitive decline has not been evaluated yet by a systematic assessment of longitudinal studies. We aimed to assess the association of persistent pain as a risk factor for cognitive decline in community older adults, using data from longitudinal studies in a systematic review and meta-analysis. Publications were identified using a systematic search on PubMed, EMBASE and Cochrane Library databases from inception to June 2019. Since heterogeneity across studies was high, we used random-effects meta-analysis to calculate the pooled relative risk for the association between persistent pain and cognitive decline incidence. We investigated sources of heterogeneity among studies using meta-regression and stratified analyses. We included ten prospective longitudinal studies with 57,495 participants with a mean age at the baseline ranging from 61.8 to 88.4 years old and mean follow-up times ranging from 2.75 to 11.8 years. Persistent pain at baseline was not associated with the development of cognitive decline during the follow-up (pooled RR = 1.05, 95% CI = 0.92-1.21). In sensitivity analyses, only length of follow-up time ≤ 4.5 years was associated with a higher risk of cognitive impairment (pooled RR = 1.19, 95% CI = 1.10-1.28). Persistent pain was not associated with the incidence of cognitive decline.

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Patterns of prescription opioid utilization among adolescents and adults with co-morbid chronic pain and mental health diagnosis.

Our goal was to examine the association between mental health disorders (MHD) and subsequent risk of opioid use among commercially insured youth and adults (ages 14-64) with co-morbid chronic non-cancer pain (CNCP) conditions. We conducted a retrospective cohort study utilizing IQVIA Health Plan Claims database from January 1, 2006 to December 31, 2015. CNCP was defined as any diagnosis of back, head, neck, arthritis, or chronic pain (index date). MHD was assessed in the 12-months prior to the index pain diagnosis. Based on days supply (none, acute, chronic) and average daily dose (none, low, medium, and high), we constructed a 7-level categorical dependent measure of opioid use. We estimated the overall prevalence of MHD and opioid receipt. Among those with CNCP, multinomial logistic regression (AOR; 95 CI) was used to estimate the association of MHD with opioid receipt. Among 879,815 individuals diagnosed with CNCP, 143,923 (16.4%) had co-morbid MHD. Chronic/high dose use of opioids was more common among those with CNCP and MHD compared to those with only CNCP. After adjusting for demographic and clinical factors, individuals with co-morbid CNCP and MHD were significantly more likely to be prescribed opioids compared to those with only CNCP conditions. This effect varied by average daily dose and days supply: acute/low dose (1.08; 1.07-1.08); chronic/low dose (1.49; 1.49-1.50); acute/medium dose (1.07; 1.07-1.08); chronic/medium dose (1.61; 1.61-1.62); acute/high dose (1.03; 1.02-1.03); and chronic/high dose (1.53; 1.53-1.54). In individuals with CNCP, having a MHD was a strong predictor of prescription opioid use, particularly chronic use.

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Interplay between body schema, visuospatial perception and pain in patients with spinal cord injury.

Changes in body representations (body image and/or body schema) have been reported in several chronic musculoskeletal pain syndromes, but rarely in patients with neuropathic pain and never in patients with spinal cord injury (SCI)-related pain.

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Clinical relevance of attentional biases in pediatric chronic pain: an eye-tracking study.

Attentional biases have been posited as one of the key mechanisms underlying the development and maintenance of chronic pain and co-occurring internalizing mental health symptoms. Despite this theoretical prominence, a comprehensive understanding of the nature of biased attentional processing in chronic pain and its relationship to theorized antecedents and clinical outcomes is lacking, particularly in youth. This study used eye-tracking to assess attentional bias for painful facial expressions and its relationship to theorized antecedents of chronic pain and clinical outcomes. Youth with chronic pain (n = 125) and without chronic pain (n = 52) viewed face images of varying levels of pain expressiveness while their eye gaze was tracked and recorded. At baseline, youth completed questionnaires to assess pain characteristics, theorized antecedents (pain catastrophizing, fear of pain, and anxiety sensitivity), and clinical outcomes (pain intensity, interference, anxiety, depression, and posttraumatic stress). For youth with chronic pain, clinical outcomes were reassessed at 3 months to assess for relationships with attentional bias while controlling for baseline symptoms. In both groups, youth exhibited an attentional bias for painful facial expressions. For youth with chronic pain, attentional bias was not significantly associated with theorized antecedents or clinical outcomes at baseline or 3-month follow-up. These findings call into question the posited relationships between attentional bias and clinical outcomes. Additional studies using more comprehensive and contextual paradigms for the assessment of attentional bias are required to clarify the ways in which such biases may manifest and relate to clinical outcomes.

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Addressing the opioid crisis: social and behavioral research contributions at the National Institutes of Health.

This commentary highlights current NIH efforts aimed at addressing the opioid crisis, specifically activities related to behavioral and social science research. Implications for this commentary will inform researchers, practitioners, and policymakers on current endeavors and future funding opportunities.

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Exploring the Psychometric Properties of the Current Opioid Misuse Measure among Adults with Chronic Pain and Opioid Use.

The opioid epidemic is a significant public health problem that is associated with overdose and death. The increase in opioid-related problems can largely be attributed to increases in opioid prescriptions for the treatment of chronic pain. Unfortunately, there is not a consensus on a definition of opioid misuse in the context of chronic pain, making measurement a challenge. One commonly used measure to assess opioid misuse in the context of chronic pain is the Current Opioid Misuse Measure (COMM). The COMM was designed to assess opioid misuse generally, as captured by psychiatric symptoms and aberrant drug use behaviors. Although studies have examined cross-validation using correlations, little psychometric work has been conducted, and therefore it is currently unknown what domains the measure is assessing.

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nNOS-expressing neurons in the vmPFC transform pPVT-derived chronic pain signals into anxiety behaviors.

Anxiety is common in patients suffering from chronic pain. Here, we report anxiety-like behaviors in mouse models of chronic pain and reveal that nNOS-expressing neurons in ventromedial prefrontal cortex (vmPFC) are essential for pain-induced anxiety but not algesia, using optogenetic and chemogenetic strategies. Additionally, we determined that excitatory projections from the posterior subregion of paraventricular thalamic nucleus (pPVT) provide a neuronal input that drives the activation of vmPFC nNOS-expressing neurons in our chronic pain models. Our results suggest that the pain signal becomes an anxiety signal after activation of vmPFC nNOS-expressing neurons, which causes subsequent release of nitric oxide (NO). Finally, we show that the downstream molecular mechanisms of NO likely involve enhanced glutamate transmission in vmPFC CaMKIIα-expressing neurons through S-nitrosylation-induced AMPAR trafficking. Overall, our data suggest that pPVT excitatory neurons drive chronic pain-induced anxiety through activation of vmPFC nNOS-expressing neurons, resulting in NO-mediated AMPAR trafficking in vmPFC pyramidal neurons.

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