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Upregulation of tumor necrosis factor-alpha in the anterior cingulate cortex contributes to neuropathic pain and pain-associated aversion.

Injury associated pain involves subjective perception and emotional experience. The anterior cingulate cortex (ACC) is a key area involved in the affective component of pain processing. However, the neuroimmune mechanisms underlying enhanced ACC excitability following peripheral nerve injury are still not fully understood. Our previous work has shown that tumor necrosis factor-alpha (TNF-α) overexpression leads to peripheral afferent hyperexcitability and synaptic transmission potentiation in spinal cord. Here, we aimed to reveal the potential role of ACC TNF-α in ACC hyperexcitability and neuropathic pain. c-Fos, a widely used neuronal activity marker, was induced especially in contralateral ACC early [postoperative (PO) 1 h] and later (PO day 7 and 10) during the development of neuropathic pain. Spared nerve injury (SNI) elevated TNF-α level in contralateral ACC from PO day 5 to 14, delayed relative to decreased ipsilateral paw withdrawal threshold apparent from PO day 1 to 14. Microinjection of anti-TNF-α antibody into the ACC completely eliminated c-Fos overexpression and greatly attenuated pain aversion and mechanical allodynia induced by SNI, suggesting an important role of ACC TNF-α in the pain aversiveness and pain maintenance. Furthermore, modulating ACC pyramidal neurons via a Gi-coupled human M4 muscarinic receptor (hM4Di) or a Gq-coupled human M3 muscarinic receptor (hM3Dq), a type of designer receptors exclusively activated by designer drugs (DREADD), greatly changed the ACC TNF-α level and the mechanical paw withdrawal threshold. The positive interactions between TNF-α and ACC neurons might modulate the cytokine microenvironment thus contribute to the neuropathic pain.

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Effectiveness of hypnosis for pain management and promotion of health-related quality-of-life among people with haemophilia: a randomised controlled pilot trial.

Joint deterioration and associated chronic pain are common among people with haemophilia (PWH), having an impact on quality-of-life. Though non-pharmacological strategies are recommended, psychological interventions to promote pain control and quality-of-life have scarcely been tested in haemophilia. This randomised controlled pilot trial aimed to assess feasibility, acceptability and effectiveness of hypnosis for pain management and promotion of health-related quality-of-life (HRQoL) among PWH. Twenty adults were randomised either to four weekly hypnosis sessions plus treatment-as-usual (experimental group; EG) or treatment-as-usual only (control group; CG). Participants completed sociodemographic and clinical assessment, measures of pain, HRQoL and emotional distress before (T1) and after (T2) intervention. Changes were analysed by calculating the differences between T1 and T2, and the groups were compared through independent-sample t tests (or chi-squared). Retention rates (90%) and analysis of patient satisfaction showed good acceptability and feasibility of the intervention. The EG (n = 8) had a higher reduction on pain interference than the CG (n = 10) (d = -0.267). A higher improvement on HRQoL (EQ-5D index: d = 0.334; EQ-5D VAS: d = 1.437) and a tendency towards better haemophilia-related quality-of-life (A36-Hemofilia QoL) were also evident in the EG. This is the first study showing the effectiveness of hypnosis to reduce pain interference and promote HRQoL among PWH.

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Peripheral Nerve Injury Triggers Neuroinflammation in the Medial Prefrontal Cortex and Ventral Hippocampus in a Subgroup of Rats with Coincident Affective Behavioural Changes.

Nerve damage leads to the development of disabling neuropathic pain in susceptible individuals, where patients present with pain as well as co-morbid affective behavioural disturbances, such as anhedonia, decreased motivation and depression. In this study we aimed to characterise changes in neuroinflammation in the medial prefrontal cortex (mPFC) and hippocampus (HP) in a rat model of neuropathic pain (NP) and behavioural changes. 53 rats underwent sciatic nerve chronic constriction injury (CCI) and were characterised as either, No effect, Acute effect or Lasting effect on the basis of changes in exploration behaviour in a radial-arm maze. Microglial and astrocyte morphology, as well as IL-1β, IL-6, IL-10, MCP-1, p38 MAPK and BDNF expression were quantified throughout the mPFC and HP using protein multiplex assays and immunofluorescence. All behavioural groups of CCI rats displayed equal levels of mechanical allodynia, however the characteristic withdrawal from pellet-seeking observed in Lasting effect rats was accompanied by neuroimmune activation within the contralateral ventral HP and mPFC. This includes increased expression of IL-1β, IL-6 and MCP-1, increased phospho-p38 MAPK expression in neurons and microglia, and a shift to a reactive microglial morphology in the caudal PL and IL, ventral CA1 and DG. Therefore, neuroinflammation in the mPFC and ventral HP may influence individual differences in radial-arm maze behaviour following CCI. Our data provide further evidence that individual differences in neuroimmune activation in the interconnected ventral HP-mPFC circuitry may play a role in the divergent behavioural trajectories following nerve injury, with neuroinflammation being coincident with affective behavioural changes in susceptible individuals.

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Different brain networks mediate the effects of social and conditioned expectations on pain.

Information about others' experiences can strongly influence our own feelings and decisions. But how does such social information affect the neural generation of affective experience, and are the brain mechanisms involved distinct from those that mediate other types of expectation effects? Here, we used fMRI to dissociate the brain mediators of social influence and associative learning effects on pain. Participants viewed symbolic depictions of other participants' pain ratings (social information) and classically conditioned pain-predictive cues before experiencing painful heat. Social information and conditioned stimuli each had significant effects on pain ratings, and both effects were mediated by self-reported expectations. Yet, these effects were mediated by largely separable brain activity patterns, involving different large-scale functional networks. These results show that learned versus socially instructed expectations modulate pain via partially different mechanisms-a distinction that should be accounted for by theories of predictive coding and related top-down influences.

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Adolescent and Parent Experiences of Acceptance and Commitment Therapy for Pediatric Chronic Pain: An Interpretative Phenomenological Analysis.

Pediatric chronic pain is common and can be related to reduced functioning in many domains for the young person and their parents. Existing psychological treatments such as Acceptance and Commitment Therapy (ACT) have shown to be effective, but improvements are needed. Qualitative approaches can help improve our understanding of treatment processes and outcomes. The aim of the present qualitative interview study was to explore the lived experiences of young people and parents who had participated in ACT for pediatric chronic pain. Four young persons and four parents were interviewed, and data was analyzed using Interpretative Phenomenological Analysis (IPA). Three themes were generated, each comprising two subthemes: (1) 'Warning system', which included experiences from being offered this psychological intervention, and the alternative explanations provided for pain; (2) 'Change and challenges', which suggested the importance of the values-based work, and of individual adaptation; and (3) 'A common language' in which the interaction with others and new ways to communicate around the pain experience were described. Findings highlight the importance of pain education, formulating and acting in line with personal values, and communication around the pain experience, as well as the need for developmental and individual adaptations of interventions.

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Healthy Lifestyle Program (HeLP) for low back pain: protocol for a randomised controlled trial.

Low back pain is one of the most common and burdensome chronic conditions worldwide. Lifestyle factors, such as excess weight, physical inactivity, poor diet and smoking, are linked to low back pain chronicity and disability. There are few high-quality randomised controlled trials that investigate the effects of targeting lifestyle risk factors in people with chronic low back pain.

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Early Changes in Pain Acceptance Predict Pain Outcomes in Interdisciplinary Treatment for Chronic Pain.

Studies have shown that pain acceptance is associated with a better pain outcome. The current study explored whether changes in pain acceptance in the very early treatment phase of an interdisciplinary cognitive-behavioral therapy (CBT)-based treatment program for chronic pain predict pain outcomes. A total of 69 patients with chronic, non-malignant pain (at least 6 months) were treated in a day-clinic for four-weeks. Pain acceptance was measured with the Chronic Pain Acceptance Questionnaire (CPAQ), pain outcomes included pain intensity (Numeric Rating Scale, NRS) as well as affective and sensory pain perception (Pain Perception Scale, SES-A and SES-S). Regression analyses controlling for the pre-treatment values of the pain outcomes, age, and gender were performed. Early changes in pain acceptance predicted pain intensity at post-treatment measured with the NRS (B = -0.04 (SE = 0.02); T = -2.28; = 0.026), affective pain perception at post-treatment assessed with the SES-A (B = -0.26 (SE = 0.10); T = -2.79; = 0.007), and sensory pain perception at post-treatment measured with the SES-S (B = -0.19 (SE = 0.08); T = -2.44; = 0.017) . Yet, a binary logistic regression analysis revealed that early changes in pain acceptance did not predict clinically relevant pre-post changes in pain intensity (at least 2 points on the NRS). Early changes in pain acceptance were associated with pain outcomes, however, the impact was beneath the threshold defined as clinically relevant.

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Depression comorbid with hyperalgesia: Different roles of neuroinflammation induced by chronic stress and hypercortisolism.

Recent studies have indicated that inflammatory pathways and hypothalamic-pituitary-adrenal (HPA) axis function may be responsible for the interaction between pain and depression.

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Neurocognitive and psychological effects of persistent pain in pediatric sickle cell disease.

Pain is a major complication of sickle cell disease (SCD), spanning vaso-occlusive crises and persistent pain. Although it is known that persistent pain is associated with considerable impairment in youth without SCD, little is known about the functional effects of persistent pain in SCD. The current study aimed to (a) characterize persistent pain in youth with SCD and (b) determine the extent to which youth with SCD and persistent pain differ in disease morbidity, functional impairment, and neurocognitive and psychological functioning.

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Acceptance and Commitment Therapy for Chronic Pain: Does Post-traumatic Stress Disorder Influence Treatment Outcomes?

The aim of this study was to determine whether post-traumatic stress disorder (PTSD) moderates treatment outcomes in Acceptance and Commitment Therapy for chronic pain.

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