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Positive Response to Galcanezumab Following Treatment Failure to OnabotulinumtoxinA in Patients With Migraine: Post hoc Analyses of 3 Randomized Double-Blind Studies.

Humanized monoclonal antibody galcanezumab, which binds to calcitonin gene-related peptide, has shown efficacy for episodic and chronic migraine prevention. These analyses evaluated galcanezumab response for migraine headache prevention in patients who previously failed onabotulinumtoxinA ("nonresponse" or "inadequate response" or safety reasons).

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Overactivity in Chronic Pain, the Role of Pain Related Endurance and Neuromuscular Activity – An Interdisciplinary, Narrative Review.

Decades of research have convincingly shown, that fear of pain and pain-related avoidance behavior are important precursors of disability in daily life. Physical underuse as a consequence of avoidance, however, cannot not be blamed for chronic disability in all patients, a contrasting behavior, pain-related dysfunctional endurance in a task and overactivity, have to be considered. Currently there is a need to better understand psychological determinants of overactivity, dysfunctional endurance and neuro-biomechanical consequences.

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Bottom-up or top-down? The role of child and parent chronic pain and anxiety in the context of parental catastrophizing and solicitousness.

Children of parents with chronic pain are a high-risk group to develop own chronic pain. There is evidence that parental responses such as catastrophizing and solicitousness play an important role in the familial transmission of chronic pain. However, little is known about factors that modulate these responses. Based on the literature, we assumed that top-down processes, such as parent chronic pain and anxiety, would be associated with increased catastrophizing and solicitousness. Bottom-up processes, such as child chronic pain and anxiety, were assumed to moderate this association. N = 118 parents (mean age: 43 years, 80.5% females) with chronic pain and/or anxiety symptoms with N = 190 children (mean age: 11 years, 49% females) were recruited in specialized hospitals and via online panels. Parents reported chronic pain, anxiety, catastrophizing, and solicitousness by use of validated questionnaires. Child pain and anxiety were assessed via parent report. Multilevel model results showed that top-down processes, rather than bottom-up processes, predicted parental responses to child's pain. Specifically, parents with more severe chronic pain reported less catastrophizing. Parent anxiety was positively associated with parental catastrophizing and solicitousness. While child chronic pain and anxiety did not exert an impact on parental responses, the parents' and child's age emerged as additional modulating factors for parental solicitousness. Findings support the assumption that top-down processes, particularly parent anxiety, rather than bottom-up processes, exert an impact on parental responses. Specific interventions to decrease parent anxiety in the context of chronic pain and effects of adult treatment on parental responses to child's pain warrant further investigation.

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Selective modulation of tonic aversive qualities of neuropathic pain by morphine in the central nucleus of the amygdala requires endogenous opioid signaling in the anterior cingulate cortex.

The amygdala is a key subcortical region thought to contribute to emotional components of pain. As opioid receptors are found in both the central (CeA) and basolateral (BLA) nuclei of the amygdala, we investigated the effects of morphine microinjection on evoked pain responses, pain motivated behaviors, dopamine release in the nucleus accumbens (NAc), and descending modulation in rats with left side spinal nerve ligation (SNL). Morphine administered into the right or left CeA had no effect on nerve injury induced tactile allodynia or mechanical hyperalgesia. Right, but not left, CeA morphine produced conditioned place preference (CPP) and increased extracellular dopamine in the NAc selectively in SNL rats, suggesting relief of aversive qualities of ongoing pain. In SNL rats, CPP and NAc dopamine release following right CeA morphine was abolished by blocking mu opioid receptor (MOR) signaling in the rostral anterior cingulate cortex (rACC). Right CeA morphine also significantly restored SNL-induced loss of the diffuse noxious inhibitory controls (DNIC), a spino-bulbo-spinal pain modulatory mechanism, termed conditioned pain modulation in humans. Microinjection of morphine into the BLA had no effects on evoked behaviors and did not produce CPP in nerve injured rats. These findings demonstrate that the amygdalar action of morphine is specific to the right CeA contralateral to the side of injury and results in enhancement of net descending inhibition. Additionally, engagement of MORs in the right CeA modulates affective qualities of ongoing pain through endogenous opioid neurotransmission within the rACC, revealing opioid-dependent functional connections from the CeA to the rACC.

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Neuroimaging features of whole-brain functional connectivity predict attack frequency of migraine.

Migraine is a chronic neurological disorder characterized by attacks of moderate or severe headache accompanying functionally and structurally maladaptive changes in brain. As the headache days/month is often measured by patient self-report and tends to be overestimated than actually experienced, the possibility of using neuroimaging data to predict migraine attack frequency is of great interest. To identify neuroimaging features that could objectively evaluate patients' headache days, a total of 179 migraineurs were recruited from two data center with one dataset used as the training/test cohort and the other used as the validating cohort. The guidelines for controlled trials of prophylactic treatment of chronic migraine in adults were used to identify the frequency of attacks and migraineurs were divided into low (MOl) and high (MOh) subgroups. Whole-brain functional connectivity was used to build multivariate logistic regression models with model iteration optimization to identify MOl and MOh. The best model accurately discriminated MOh from MOl with AUC of 0.91 (95%CI [0.86, 0.95]) in the training/test cohort and 0.79 in the validating cohort. The discriminative features were mainly located within the limbic lobe, frontal lobe, and temporal lobe. Permutation tests analysis demonstrated that the classification performance of these features was significantly better than chance. Furthermore, the indicator of functional connectivity had a higher odds ratio than behavioral variables with implementing a holistic regression analysis. The current findings suggested that the migraine attack frequency could be distinguished by using machine-learning algorithms, and highlighted the role of brain functional connectivity in revealing underlying migraine-related neurobiology.

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Patients with fibromyalgia reporting severe pain but low impact of the syndrome: clinical and pain-related cognitive features.

Fibromyalgia (FM) is a prevalent and highly disabling chronic pain syndrome. However, differences among patients regarding how pain impacts on daily life are remarkable. The main aim of this study was to identify clinical and pain-related cognitive variables characterizing patients reporting high adaptability despite experiencing severe chronic pain.

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Episodic and Chronic Cluster Headache: Differences in Family History, Traumatic Head Injury, and Chronorisk.

The diagnostic criteria of episodic and chronic cluster headache (cCH) were recently modified, yet pathophysiological differences between the two are still unclear. The aim of this cross-sectional study is to identify and characterize other differences between episodic and cCH.

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Dynamic Pressure Pain Hypersensitivity as Assessed by Roller Pressure Algometry in Episodic Cluster Headache.

A method for assessing dynamic muscle hyperalgesia (dynamic pressure algometry) has been developed and applied in tension-type and migraine headaches.

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Abnormal cardiovascular response to nitroglycerin in migraine.

Migraine and vasovagal syncope are comorbid conditions that may share part of their pathophysiology through autonomic control of the systemic circulation. Nitroglycerin can trigger both syncope and migraine attacks, suggesting enhanced systemic sensitivity in migraine. We aimed to determine the cardiovascular responses to nitroglycerin in migraine.

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Psychological Subgrouping to Assess the Risk for the Development or Maintenance of Chronic Musculoskeletal Pain: Is This the Way Forward?

Because musculoskeletal pain problems are so prevalent, new methods of evaluating and treating patients are needed to increase effectiveness. Subgrouping is a method where patients are classified into defined groups based on psychosocial factors with the expectation of more specific and tailored treatments for them. For those seeking care for a new episode, the risk of developing chronic pain-related disability is assessed, while for those with existing pain the risk for the maintenance of the chronic pain problem is evaluated. In this narrative review we examine the subgrouping of patients with regard to methods of evaluation as well as to whether subgrouping actually facilitates treatment. For the development of disability, screening tools e.g. the Örebro Musculoskeletal Pain Screening Questionnaire accurately stratify patients into group (e.g. high, medium, low risk) that predict future pain-related work disability. In addition, several studies show that treatments that directly key on risk groups enjoy enhanced outcomes compared to treatment as usual. For the maintenance of chronic musculoskeletal pain problems there are several instruments that classify patients into specific groups or profiles e.g. based on the avoidance and endurance model or the ICF assessment. While some evidence shows that these classifications are related to treatment outcome, we found no study that directly tested a system for providing treatment matched to the subgrouping for maintenance. We conclude that it is possible to reliably subgroup patients with musculoskeletal problems. Likewise, treatments that address the risk factors in the screening procedure, may enhance outcomes compared to treatment as usual. More work is needed however, to better understand mechanism so assessment methods can be improved and treatment specific to subgroups can be developed.

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