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Identification of novel common variants associated with chronic pain using conditional false discovery rate analysis with major depressive disorder and assessment of pleiotropic effects of LRFN5.

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Pilot Study of an Internet-Based Self-Management Program for Symptom Control in Patients With Early-Stage Breast Cancer.

Many survivors of breast cancer experience an array of chronic symptoms, including pain, insomnia, and fatigue. Few effective therapies have been identified. Behavioral management programs to address similar symptom clusters in other chronic conditions have been effective. The objective of this study was to determine the effect of an Internet-based lifestyle and behavioral self-management program on cancer-related symptoms.

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Sex Differences in Nociceptin/Orphanin FQ Peptide Receptor-Mediated Pain and Anxiety Symptoms in a Preclinical Model of Post-traumatic Stress Disorder.

Nociceptin/Orphanin FQ (N/OFQ) is a neuropeptide that modulates pain transmission, learning/memory, stress, anxiety, and fear responses via activation of the N/OFQ peptide (NOP or ORL1) receptor. Post-traumatic stress disorder (PTSD) is an anxiety disorder that may arise after exposure to a traumatic or fearful event, and often is co-morbid with chronic pain. Using an established animal model of PTSD, single-prolonged stress (SPS), we were the first to report that NOP receptor antagonist treatment reversed traumatic stress-induced allodynia, thermal hyperalgesia, and anxiety-like behaviors in male Sprague-Dawley rats. NOP antagonist treatment also reversed SPS-induced serum and CSF N/OFQ increase and circulating corticosterone decrease. The objective of this study was to examine the role of the NOP receptor in male and female rats subjected to traumatic stress using Wistar wild type (WT) and NOP receptor knockout (KO) rats. The severity of co-morbid allodynia was assessed as change in paw withdrawal threshold (PWT) to von Frey and paw withdrawal latency (PWL) to radiant heat stimuli, respectively. PWT and PWL decreased in male and female WT rats within 7 days after SPS, and remained decreased through day 28. Baseline sensitivity did not differ between genotypes. However, while male NOP receptor KO rats were protected from SPS-induced allodynia and thermal hypersensitivity, female NOP receptor KO rats exhibited tactile allodynia and thermal hypersensitivity to the same extent as WT rats. Male NOP receptor KO rats had a lower anxiety index (AI) than WT, but SPS did not increase AI in WT males. In contrast, SPS significantly increased AI in WT and NOP receptor KO female rats. SPS increased circulating N/OFQ levels in male WT, but not in male NOP receptor KO, or WT or KO female rats. These results indicate that the absence of the NOP receptor protects males from traumatic-stress-induced allodynia and hyperalgesia, consistent with our previous findings utilizing a NOP receptor antagonist. However, female NOP receptor KO rats experience allodynia, hyperalgesia and anxiety-like symptoms to the same extent as WT females following SPS. This suggests that endogenous N/OFQ-NOP receptor signaling plays an important, but distinct, role in males and females following exposure to traumatic stress.

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Attentional Engagement for Pain-Related Information among Individuals with Chronic Pain: The Role of Pain Catastrophizing.

Although the evidence of the attentional bias of chronic pain individuals toward pain-related information is established in the literature, few studies examined the time course of attention toward pain stimuli and the role of pain catastrophizing on attentional engagement toward pain-related information. This study examined the time course of attention to pain-related information and the role of pain catastrophizing on attentional engagement for pain-related information. Participants were fifty young adult participants with chronic pain (35% male, 65% female; M = 21.8 years) who completed self-report questionnaires assessing pain catastrophizing levels (Pain Catastrophizing Scale (PCS)), depression (the Center for Epidemiologic Studies Depression Scale (CES-D)), anxiety (State-Trait Anxiety Inventory (STAI)), and pain disability (the Pain Disability Index: (PDI)). Attentional engagements to pain- and anger-related information were measured by the eye tracker. Significant interaction effects were found between (1) time and stimulus type for pain-related information ( (5, 245) = 11.55, < 0.001) and (2) bias scores and pain catastrophizing ( (1, 48) = 6.736, < 0.05). These results indicated that the degree of increase for pain bias scores were significantly greater than anger bias scores as levels of pain catastrophizing increased. Results of the present study provided the evidence for the attentional bias and information processing model which has clinical implications; high levels of pain catastrophizing may impair individuals' ability to cope with chronic pain by increasing attentional engagement toward pain-related information. The present study can add knowledge to attentional bias and pain research as this study investigated the time course of attention and the role of pain catastrophizing on attentional engagement toward pain-related information for adults with chronic pain conditions.

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Greater mechanical temporal summation of pain in Latinx-Americans and the role of adverse life experiences.

Adverse life experiences disproportionately impact Latinx-Americans and are related to greater chronic pain rates. However, little is known about how adversities interact with central pain mechanisms for the development of later pain among Latinx-Americans.

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Placebos in chronic pain: evidence, theory, ethics, and use in clinical practice.

Despite their ubiquitous presence, placebos and placebo effects retain an ambiguous and unsettling presence in biomedicine. Specifically focused on chronic pain, this review examines the effect of placebo treatment under three distinct frameworks: double blind, deception, and open label honestly prescribed. These specific conditions do not necessarily differentially modify placebo outcomes. Psychological, clinical, and neurological theories of placebo effects are scrutinized. In chronic pain, conscious expectation does not reliably predict placebo effects. A supportive patient-physician relationship may enhance placebo effects. This review highlights "predictive coding" and "bayesian brain" as emerging models derived from computational neurobiology that offer a unified framework to explain the heterogeneous evidence on placebos. These models invert the dogma of the brain as a stimulus driven organ to one in which perception relies heavily on learnt, top down, cortical predictions to infer the source of incoming sensory data. In predictive coding/bayesian brain, both chronic pain (significantly modulated by central sensitization) and its alleviation with placebo treatment are explicated as centrally encoded, mostly non-conscious, bayesian biases. The review then evaluates seven ways in which placebos are used in clinical practice and research and their bioethical implications. In this way, it shows that placebo effects are evidence based, clinically relevant, and potentially ethical tools for relieving chronic pain.

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“Bearing the Pain”: The Experience of Aging African Americans With Osteoarthritis Pain.

Studies document that osteoarthritis-related joint pain is more severe in African American older adults, but research on the personal experience of osteoarthritis pain self-management in this population is limited. Using a qualitative descriptive design, our objective was to extend our understanding of the experience of life with osteoarthritis pain. Eighteen African Americans (50 years and older) were recruited from Louisiana to participate in a single semi-structured, in-depth interview. A conventional content analysis revealed that "Bearing the pain" characterized how older African Americans dealt with osteoarthritis. Bearing the pain comprised three actions: adjusting to pain, sharing pain with others, and trusting God as healer. We discovered that a metapersonal experience subsumes the complex biopsychosocial-cultural patterns and the intricate interaction of self, others, and God in living with and managing osteoarthritis pain. Study findings have implications for application of more inclusive self-management frameworks and interventions.

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CD3 T cells are critical for the resolution of comorbid inflammatory pain and depression-like behavior.

Chronic pain and depression often co-occur. The mechanisms underlying this comorbidity are incompletely understood. Here, we investigated the role of CD3 T cells in an inflammatory model of comorbid persistent mechanical allodynia, spontaneous pain, and depression-like behavior in mice.

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The Effects of Acute Neonatal Pain on Expression of Corticotropin Releasing Hormone and Juvenile Anxiety in a Rodent Model.

Premature infants in the Neonatal Intensive Care Unit (NICU) may be subjected to numerous painful procedures without analgesics. One necessary, though acutely painful, procedure is the use of heel lances to monitor blood composition. The current study examined the acute effects of neonatal pain on maternal behavior as well as amygdalar and hypothalamic activation, and the long-term effects of neonatal pain on later-life anxiety-like behavior, using a rodent model. Neonatal manipulations consisted of either painful needle pricks or non-painful tactile stimulation in subjects' left plantar paw surface which occurred four times daily during the first week of life (PND 1 – 7). Additionally, maternal behaviors in manipulated litters were compared against undisturbed litters via scoring of videotaped interactions to examine the long-term effects of pain on dam-pup interactions. Select subjects underwent neonatal brain collection (PND 6) and fluorescent hybridization (FISH) for corticotropin releasing hormone (CRH) and the immediate early gene c-fos. Other subjects were raised to juvenile age (PND 24 and PND 25) and underwent innate anxiety testing utilizing an elevated plus maze protocol. FISH indicated that neonatal pain influenced amygdalar CRH and c-fos expression, predominately in males. No significant increase in c-fos or CRH expression was observed in the hypothalamus. Additionally, neonatal pain altered anxiety behaviors independent of sex, with neonatal pain subjects showing the highest frequency of exploratory behavior. Neonatal manipulations did not alter maternal behaviors. Overall, neonatal pain drives CRH expression and produces behavioral changes in anxiety that persist until the juvenile stage. This report expands on current rodent model research performed to assess the long-term effects of highly utilized neonatal intensive care unit (NICU) procedures. The NICU plays an integral role in pediatric medicine by significantly reducing infant mortality and providing necessary procedures to preterm or unwell newborns. However, procedures in the NICU are often stressful and painful. A common procedure performed in the NICU is heel lances to monitor blood composition. This, along with numerous other painful procedures, are often performed on NICU babies without the benefit of analgesics. Our study identifies key neurological indicators which are altered in response to neonatal pain. Additionally, we explore the later anxiety of subjects exposed to neonatal pain.

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Proposal for Improvement of the Hospital Anxiety and Depression Scale for the Assessment of Emotional Distress in Patients with Chronic Musculoskeletal Pain: a Bifactor and Item Response Theory Analysis.

The Hospital Anxiety and Depression Scale (HADS) is a scale originally developed for the assessment of anxiety and depression in hospitalized patients. Despite its wide diffusion, the HADS factorial structure has displayed inconsistent results, leaving doubts about its use in chronic musculoskeletal pain. The purpose of this study was to thoroughly assess the factorial structure of the HADS in patients with chronic pain and to give guidance for a potential refinement. Data from 2522 patients with chronic pain from the Amsterdam Pain (AMS-PAIN) cohort were analyzed through: (1) exploratory bifactor analysis based on a Schmid-Leiman orthogonalization, (2) confirmatory factor analysis comparing a unidimensional model, the original correlated factors model and a bifactor model, (3) item response theory (IRT) analysis based on the graded response model. The results of the confirmatory factor analysis and of the IRT analysis were then cross – validated in an independent sample of patients with chronic pain (n = 8604). Both exploratory and confirmatory analyses revealed the presence of a strong general emotional distress factor, suggesting that the HADS can be used as a unidimensional scale. The IRT analysis led to the exclusion of three items and to the recoding of one item. The refined 11-item HADS scale was successfully cross-validated and confirmed as a unidimensional, locally independent, monotonic and reliable scale. Perspective: An 11-item shorter version of the HADS could be used to measure emotional distress in patients with chronic musculoskeletal pain. Given its unidimensionality, the use of its total score seems appropriate.

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