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Anxiety sensitivity and intentional avoidance of physical activity in women with probable migraine.

Avoidance of physical activity is a common migraine management strategy. Anxiety sensitivity (i.e. fear of anxiety and bodily sensations due to physical, cognitive, or social consequences) is a potential correlate of physical activity avoidance and may strengthen beliefs about physical activity's detrimental effect on migraine.

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Prevalence and pathophysiology of post-prandial migraine in patients with functional dyspepsia.

Migraine is a condition frequently associated with gastrointestinal disorders. Previous reports have shown the relationship between irritable bowel syndrome and migraine, but no data are yet available in patients with functional dyspepsia. We therefore evaluated whether alteration of gastric sensorimotor activity may be related to migraine.

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Structural and functional alterations in the retrosplenial cortex following neuropathic pain.

Human and animal imaging studies demonstrated that chronic pain profoundly alters the structure and the functionality of several brain regions. Herein, we conducted a longitudinal and multimodal study to assess how chronic pain affects the brain. Using the Spared Nerve Injury model (SNI) which promotes both long-lasting mechanical and thermal allodynia/hyperalgesia but also pain-associated comorbidities, we showed that neuropathic pain deeply modified the intrinsic organization of the brain functional network one and two months after injury. We found that both functional metrics and connectivity of the part A of the retrosplenial granular cortex (RSgA) were significantly correlated with the development of neuropathic pain behaviours. Additionally, we found that the functional RSgA connectivity to the subiculum and the prelimbic system are significantly increased in SNI animals and correlated with peripheral pain thresholds. These brain regions were previously linked to the development of comorbidities associated with neuropathic pain. Using a Voxel-Based Morphometry approach, we showed that neuropathic pain induced a significant increase of the grey matter concentration within the RSgA, associated with a significant activation of both astrocytes and microglial cells. Together, functional and morphological imaging metrics of the RSgA could be used as a predictive biomarker of neuropathic pain.

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Investigating macrophage-mediated inflammation in migraine using ultrasmall superparamagnetic iron oxide-enhanced 3T magnetic resonance imaging.

Initiating mechanisms of migraine headache remain poorly understood and a biomarker of migraine does not exist. Inflammation pertaining to the wall of cerebral arteries and brain parenchyma has been suggested to play a role in migraine pathophysiology.

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Adverse Childhood Experiences in Mothers with Chronic Pain and Intergenerational Impact on Children.

Adverse childhood experiences (ACEs; e.g., parental divorce, physical or sexual abuse) are more prevalent in individuals with chronic pain compared to the general population. Both increased maternal ACEs and chronic pain have been associated with poor physical and emotional functioning in offspring. However, the mechanisms driving these associations are poorly understood. Thus, this cross-sectional study evaluated the relation between maternal ACEs, mothers' current functioning, and children's physical and emotional functioning in a sample of mothers with chronic pain and their 8-12 year-old children. Results indicated a higher prevalence of at least 1 ACE in this sample of mothers with chronic pain (84%) compared to normative data from a community sample of women. Higher maternal ACE scores corresponded with lower physical and social functioning, greater anxiety and depressive symptoms, greater fatigue and sleep disturbances, and greater pain intensity and pain interference in mothers. Higher maternal ACE scores significantly correlated with higher child self-reported depressive symptoms, but not somatic symptoms or functional impairment. A path model indicated that maternal depressive symptoms accounted for the relation between higher maternal ACE scores and children's depressive symptoms. Intervening on maternal depression among mothers with chronic pain may reduce the impact of intergenerational ACE transmission. Perspective: This article presents evidence regarding the intergenerational impact of adverse childhood experiences in a large sample of mothers with chronic pain and their school-aged children. Maternal depressive symptoms accounted for the relation between maternal ACEs and children's depressive symptoms providing evidence regarding targets for preventive interventions.

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A randomized controlled trial testing a virtual perspective-taking intervention to reduce race and socioeconomic status disparities in pain care.

We conducted a randomized controlled trial of an individually tailored, virtual perspective-taking intervention to reduce race and socioeconomic status (SES) disparities in providers' pain treatment decisions. Physician residents and fellows (n = 436) were recruited from across the United States for this two-part online study. Providers first completed a bias assessment task in which they made treatment decisions for virtual patients with chronic pain who varied by race (black/white) and SES (low/high). Providers who demonstrated a treatment bias were randomized to the intervention or control group. The intervention consisted of personalized feedback about their bias, real-time dynamic interactions with virtual patients, and videos depicting how pain impacts the patients' lives. Treatment bias was re-assessed 1 week later. Compared with the control group, providers who received the tailored intervention had 85% lower odds of demonstrating a treatment bias against black patients and 76% lower odds of demonstrating a treatment bias against low SES patients at follow-up. Providers who received the intervention for racial bias also showed increased compassion for patients compared with providers in the control condition. Group differences did not emerge for provider comfort in treating patients. Results suggest an online intervention that is tailored to providers according to their individual treatment biases, delivers feedback about these biases, and provides opportunities for increased contact with black and low SES patients, can produce substantial changes in providers' treatment decisions, resulting in more equitable pain care. Future studies should examine how these effects translate to real-world patient care and the optimal timing/dose of the intervention.

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A neuronal circuit for activating descending modulation of neuropathic pain.

Neuropathic pain can be a debilitating condition with both sensory and affective components, the underlying brain circuitry of which remains poorly understood. In the present study, a basolateral amygdala (BLA)-prefrontal cortex (PFC)-periaqueductal gray (PAG)-spinal cord pathway was identified that is critical for the development of mechanical and thermal hypersensitivity after peripheral nerve injury. It was shown that nerve injury strengthens synaptic input from the BLA onto inhibitory interneurons located in the prelimbic medial PFC, by virtue of reduced endocannabinoid modulation. These augmented synaptic connections mediate a feedforward inhibition of projections from the PFC to the ventrolateral PAG region and its downstream targets. Optogenetic approaches combined with in vivo pharmacology reveal that these BLA-PFC-PAG connections alter pain behaviors by reducing descending noradrenergic and serotoninergic modulation of spinal pain signals. Thus, a long-range brain circuit was identified that is crucial for pain processing and that can potentially be exploited toward targeting neuropathic pain.

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Patient-reported outcome measures for acute and chronic pain: current knowledge and future directions.

During the past years, patient-reported outcomes (PROs) and patient-reported outcome measures (PROMs) have become of growing awareness and importance in medical research and practice. This review summarizes recent developments concerning PROs and PROMs related to pain in the acute postoperative as well as chronic settings and indicates gaps and challenges relevant for future research and clinical applications.

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Cannabis-based medicines for chronic pain management: current and future prospects.

The medicinal use of cannabis has recently become the focus of much medical, as well as political, attention. This reality of growing use but limited evidence creates unique dilemmas for the prescribing clinician. The purpose of this review is to explore current evidence and gaps in knowledge and offer some practical considerations.

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Opioid-induced signaling and antinociception are modulated by the recently deorphanized receptor, GPR171.

ProSAAS is one of the most widely expressed proteins throughout the brain and has recently been found to be upregulated in chronic fibromyalgia patients. BigLEN is a neuropeptide that is derived from ProSAAS and was recently discovered to be the endogenous ligand for the orphan G protein-coupled receptor, GPR171. While BigLEN- GPR171 has been found to play a role in feeding and anxiety behaviors, it has not yet been explored in pain and opioid modulation. The purpose of this study was to evaluate this novel neuropeptide-receptor system in opioid-induced antinociception. We found that GPR171 is expressed in GABAergic neurons within the periaqueductal gray (PAG), which is a key brain area involved in pain modulation and opioid functions. We also found that although the GPR171 agonist and antagonist do not have nociceptive effects on their own, they oppositely regulate morphine-induced antinociception with the agonist enhancing and antagonist reducing antinociception. Lastly, we showed that the GPR171 antagonist or receptor knockdown decreases signaling by the mu-opioid receptor, but not the delta-opioid receptor. Taken together, these results suggest that antagonism of the GPR171 receptor reduces MOPr signaling and morphine induced-antinociception, whereas the GPR171 agonist enhances morphine antinociception suggesting that GPR171 may be a novel target towards the development of pain therapeutics. SIGNIFICANCE STATEMENT: GPR171 is a recently deorphanized receptor that is expressed within the periaqueductal gray and can regulate mu opioid receptor signaling and antinociception. This research may contribute to the development of new therapeutics to treat pain.

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