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Adverse childhood experiences and chronic pain among children and adolescents in the United States.

To evaluate the association between adverse childhood experiences (ACEs) and chronic pain during childhood and adolescence.

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Pain-Related Nucleus Accumbens Function: Modulation by Reward and Sleep Disruption.

The nucleus accumbens (NAc) has been implicated in sleep, reward, and pain modulation, but the relationship between these functional roles is unclear. This study aimed to determine if NAc function at the onset and offset of a noxious thermal stimulus is enhanced by rewarding music, and if that effect is reversed by experimental sleep disruption. Twenty-one healthy subjects underwent functional MRI (fMRI) scans on two separate days following both uninterrupted sleep and experimental sleep disruption. During fMRI scans, participants experienced noxious stimulation while listening to individualized rewarding or neutral music. Behavioral results revealed that rewarding music significantly reduced pain intensity compared to neutral music and disrupted sleep was associated with decreased pain intensity in the context of listening to music. In whole-brain FWE cluster-corrected analysis, NAc was activated at pain onset, but not during tonic pain or at pain offset. Sleep disruption attenuated NAc activation at pain onset and during tonic pain. Rewarding music altered NAc connectivity with key nodes of the corticostriatal circuits during pain onset. Sleep disruption increased reward-related connectivity between the NAc and the anterior midcingulate cortex (aMCC) at pain onset. This study thus indicates that experimental sleep disruption modulates NAc function during the onset of pain in a manner that may be conditional on the presence of competing reward-related stimuli. These findings point to potential mechanisms for the interaction between sleep, reward, and pain, and suggest that sleep disruption affects both the detection and processing of aversive stimuli that may have important implications for chronic pain.

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Resting state functional connectivity and cognitive task-related activation of the human claustrum.

Structural and functional analyses of the human claustrum, a poorly understood telencephalic gray matter structure, are hampered by its sheet-like anatomical arrangement. Here, we first describe a functional magnetic resonance imaging (fMRI) method to reveal claustrum signal with no linear relationship with adjacent regions in human subjects. We applied this approach to resting state functional connectivity (RSFC) analysis of the claustrum at high resolution (1.5 mm isotropic voxels) using a 7T dataset (n = 20) and a separate 3T dataset for replication (n = 35). We then assessed claustrum activation during performance of a cognitive task, the multi-source interference task, at 3T (n = 33). Extensive functional connectivity was observed between claustrum and cortical regions associated with cognitive control, including anterior cingulate, prefrontal and parietal cortices. Cognitive task performance was associated with widespread activation and deactivation that overlapped with the cortical areas showing functional connectivity to the claustrum. Furthermore, during high cognitive conflict conditions of the task, the claustrum was significantly activated at the onset of the task, but not during the remainder of the difficult condition. Both of these findings suggest that the human claustrum can be functionally isolated with fMRI, and that it may play a role in cognitive control, and specifically task switching, independent of sensorimotor processing.

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The neural mechanisms of mindfulness-based pain relief: a functional magnetic resonance imaging-based review and primer.

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How to prevent, minimize, or extinguish nocebo effects in pain a narrative review on mechanisms, predictors, and interventions.

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Does bedtime matter among patients with chronic pain? A longitudinal comparison study.

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SIRT1 decreases emotional pain vulnerability with associated CaMKIIα deacetylation in central amygdala.

Emotional disorders are common comorbid conditions that further exacerbate the severity and chronicity of chronic pain. However, individuals show considerable vulnerability to developing chronic pain under similar pain conditions. In this study on male rat and mouse models of chronic neuropathic pain, we identify the histone deacetylase SIRT1 in central amygdala as a key epigenetic regulator that controls the development of comorbid emotional disorders underlying the individual vulnerability to chronic pain. We found that animals that were vulnerable to developing behaviors of anxiety and depression under the pain condition displayed reduced SIRT1 protein in central amygdala, but not those animals resistant to the emotional disorders. Viral overexpression of local SIRT1 reversed this vulnerability, but viral knockdown of local SIRT1 mimicked the pain effect, eliciting the pain vulnerability in pain-free animals. The SIRT1 action was associated with CaMKIIα downregulation and deacetylation of histone H3 lysine 9 at the promoter. These results suggest that, by transcriptional repression of in central amygdala, SIRT1 functions to guard against the emotional pain vulnerability under chronic pain conditions. This study indicates that SIRT1 may serve as a potential therapeutic molecule for individualized treatment of chronic pain with vulnerable emotional disorders.Chronic pain is a prevalent neurological disease with no effective treatment at present. Pain patients display considerably variable vulnerability to developing chronic pain, indicating individual-based molecular mechanisms underlying the pain vulnerability, which is hardly addressed in current preclinical research. In this study, we have identified the histone deacetylase Sirtuin 1 (SIRT1) as a key regulator that controls this pain vulnerability. This study reveals that the SIRT1–CaMKIIaα pathway in central amygdala acts as an epigenetic mechanism that guards against the development of comorbid emotional disorders under chronic pain, and that its dysfunction causes increased vulnerability to developing chronic pain. These findings suggest that SIRT1 activators may be used in a novel therapeutic approach for individual-based treatment of chronic pain.

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Can slow deep breathing reduce pain? An experimental study exploring mechanisms.

Slow deep breathing (SDB) is commonly employed in the management of pain, but the underlying mechanisms remain equivocal. This study sought to investigate effects of instructed breathing patterns on experimental heat pain and to explore possible mechanisms of action. In a within-subject experimental design, healthy volunteers (n = 48) performed four breathing patterns: 1) unpaced breathing (UB), 2) paced breathing at the participant's spontaneous breathing frequency (PB), 3) SDB at six breaths per minute with a high inspiration/expiration ratio (SDB-H), and 4) SDB at six breaths per minute with a low inspiration/expiration ratio (SDB-L). During presentation of each breathing pattern, participants received painful heat stimuli of three different temperatures and rated each stimulus on pain intensity. Respiration, heart rate, and blood pressure were recorded. Compared to UB, participants reported less intense pain during each of the three instructed breathing patterns. Among the instructed breathing patterns, pain did not differ between PB and SDB-H, and SDB-L attenuated pain more than the PB and SDB-H patterns. The latter effect was paralleled by greater blood pressure variability and baroreflex effectiveness index during SDB-L. Cardiovascular changes did not mediate the observed effects of breathing patterns on pain. Perspective: SDB is more efficacious to attenuate pain when breathing is paced at a slow rhythm with an expiration that is long relative to inspiration, but the underlying mechanisms remain to be elucidated.

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Therapeutic and Preventive Effect of Voluntary Running Wheel Exercise on Social Defeat Stress (SDS)-induced Depressive-like Behavior and Chronic Pain in Mice.

Major depressive disorders (MDD) and chronic pain (CP) affect significant portion of the world's population and have high comorbidity rate. Social defeat stress (SDS) model was standardized in mice and can trigger depressive-like behavior and chronic pain. Based especially on clinical trials showing an effective preventive and therapeutic effect of physical exercise on CP and symptoms associated with MDD, this study aimed to investigate if the voluntary running wheel exercise can exert these effects in mice submitted to the 10-day SDS protocol, using fluoxetine as positive control. For this, we ran two set of experiments: in the first set mice started performing voluntary running wheel exercise after submitted to SDS and, in the second set, mice performed voluntary running wheel exercise before and during SDS. Mechanical and chemical hyperalgesia was analyzed through electronic von Frey and capsaicin test, respectively. Depressive-like behavior was assessed through social interaction test. Our results showed that the voluntary running wheel exercise was more effective than fluoxetine reversing the SDS-induced persistent hyperalgesia and both, fluoxetine and voluntary running wheel exercise, was effective reversing SDS-induced social avoidance. Also, voluntary running wheel exercise is an effective tool preventing both hyperalgesia and social avoidance induced by SDS. To the best of our knowledge, this was the first study using physical exercise as a therapeutic and preventive tool for chronic pain and depressive-like behavior simultaneously induced by social stress.

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Doctor recommendations are related to patient interest and use of behavioral treatment for chronic pain and addiction.

The opioid crisis has highlighted the importance of improving patients' access to behavioral treatments for chronic pain and addiction. What is not known is if patients are interested in receiving these treatments. In this cross-sectional study, over 1000 participants with chronic pain were surveyed using an anonymous online questionnaire on Amazon Mechanical Turk (Mturk) to investigate participants' use of and interest in pharmacological and behavioral treatments for chronic pain and addiction. Participants also indicated whether their doctor had recommended these treatments. The majority of participants reported using medication for their pain (83.19%) and that their doctor recommended medication (85.05%), whereas fewer participants reported using (67.45%) and being recommended to (62.82%) behavioral treatments. We found 63.67% of participants screened positive for possible opioid misuse; those who screened positive were more interested in receiving behavioral treatments than those who did not screen positive. Participants who received treatment recommendations were more likely to be interested in receiving those treatments as compared to participants who did not. The results suggest that recommendations for behavioral treatments and interest in those treatments are related. Results also suggest that patients endorsing behaviors consistent with opioid misuse are interested in behavioral treatments. Perspective: This study provides information around chronic pain patients' treatment interests, treatment receipt, and recommendation receipt for behavioral pain management and addiction treatment. This study could help facilitate communication between patients and doctors regarding available treatments for chronic pain and pain treatment-related addiction problems.

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