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Cluster headache: insights from resting-state functional magnetic resonance imaging.

The comprehension of cluster headache (CH) has greatly benefited from the tremendous progress of the neuroimaging techniques over the last 20 years. Since the pioneering study of May et al. (1998), the neuroimaging results have indeed revolutionized the conception of this disease, now considered as a dysfunction of the central nervous system. Clinical, neuroendocrinological, and neuroimaging studies strongly suggested the involvement of the hypothalamus as the generator of cluster headache attacks. However, the latency of the improvement and the inefficacy of the hypothalamic deep brain stimulation (DBS) in the acute phase suggested that the hypothalamus might play a modulating role, pointing to the presence of some dysfunctional brain networks, normalized or modulated by the DBS. Despite the great importance of possible dysfunctional hypothalamic networks in cluster headache pathophysiology, only quite recently the scientific community has begun to explore the functional connectivity of these circuits using resting-state functional magnetic resonance imaging. This is a neuroimaging technique extensively employed to investigate the functional connectivity among separated regions of the brain at rest in the low-frequency domain (< 0.1 Hz). Here, we present a review of the few resting-state functional magnetic resonance imaging studies investigating the hypothalamic network contributing to a deeper comprehension of this neurological disorder. These studies seem to demonstrate that both the hypothalamus and the diencephalic-mesencephalic junction regions might play an important role in the pathophysiology of CH. However, future studies are needed to confirm the results and to clarify if the observed dysfunctional networks are a specific neural fingerprint of the CH pathophysiology or an effect of the severe acute pain. It will be also crucial to clarify the neural pathways of the chronicization of this disorder.

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Responding to social cues: An experimental paradigm exploring the link between context sensitivity and pain.

The term context sensitivity refers to whether a response is in tune with the ever changing demands of the context, while insensitivity is the lack of responding to these cues. To date, we know little about how well patients with pain respond emotionally to changes in the cues provided by the social context, that is, how emotionally context (in)sensitive they are and if this is related to problem severity. The aim of this experimental study was to test a method for determining levels of context sensitivity in individuals with subacute and chronic pain and to explore the link between context (in)sensitivity and pain-related problems. We operationalized context (in)sensitivity as participants' emotional responses (observed facial expressions and self-reported affect) and pain bothersomeness in these contexts and explored the association between these context-(in)sensitive social-emotional responses and pain-related problems.

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ACT for migraine: effect of acceptance and commitment therapy (ACT) for high-frequency episodic migraine without aura: preliminary data of a phase-II, multicentric, randomized, open-label study.

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Opioid-free anaesthesia – what would Inigo Montoya say?

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Ketamine infusion for 96 hr after thoracotomy: Effects on acute and persistent pain.

Pain which persists after thoracotomy is well recognized, and activation of the N-methyl-d-aspartate (NMDA) receptor could be a contributing factor. This study sought to establish whether ketamine given peri-operatively could reduce persistent post-surgical pain.

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Trigeminal neuropathic pain development and maintenance in rats are suppressed by a positive modulator of α6GABA receptors.

GABA receptors containing the α6 subunit are located in trigeminal ganglia, and their reduction by small interfering RNA increases inflammatory temporomandibular and myofascial pain in rats. We thus hypothesized that enhancing their activity may help in neuropathic syndromes originating from the trigeminal system. Here, we performed a detailed electrophysiological and pharmacokinetic analysis of two recently developed deuterated structurally similar pyrazoloquinolinone compounds. DK-I-56-1 at concentrations below 1 μM enhanced GABA currents at recombinant rat α6β3γ2, α6β3δ and α6β3 receptors whereas it was inactive at most GABA receptor subtypes containing other α subunits. DK-I-87-1 at concentrations below 1 μM was inactive at α6-containing receptors and only weakly modulated other GABA receptors investigated. Both plasma and brain tissue kinetics of DK-I-56-1 were relatively slow, with half-lives of 6 h and 13 h, respectively, enabling the persistence of estimated free brain concentrations in the range 10-300 nM throughout a 24-h period. Results obtained in two protocols of chronic constriction injury of the infraorbital nerve in rats dosed intraperitoneally with DK-I-56-1 during 14 days after surgery, or with DK-I-56-1 or DK-I-87-1 during 14 days after trigeminal neuropathy was already established, demonstrated that DK-I-56-1 but not DK-I-87-1 significantly reduced the hypersensitivity response to von Frey filaments. This article is protected by copyright. All rights reserved.

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Efficacy and safety of ASP1707 for endometriosis-associated pelvic pain: the phase II randomized controlled TERRA study.

Does the GnRH antagonist, ASP1707, reduce endometriosis-associated pelvic pain?

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Alexithymia in individuals with chronic pain and its relation to pain intensity, physical interference, depression, and anxiety: a systematic review and meta-analysis.

Numerous studies have examined how alexithymia (difficulty identifying and describing one's emotions and a preference for externally oriented thinking) relates to chronic pain and associated disability. We conducted a systematic review and meta-analysis to summarize individual studies that either assessed alexithymia in individuals with chronic pain vs controls or related alexithymia to pain intensity, physical interference, depression, and anxiety. We searched MEDLINE, Embase, and PsycINFO from inception through June 2017; 77 studies met the criteria (valid assessment of alexithymia in adults or children with any chronic pain condition) and were included in analyses (n = 8019 individuals with chronic pain). Primary analyses indicated that chronic pain samples had significantly higher mean alexithymia scores compared with nonclinical (d = 0.81) and clinical nonpain (d = 0.55) controls. In chronic pain samples, alexithymia was significantly positively associated with pain intensity (d = 0.20), physical interference (d = 0.17), depression (d = 0.46), and anxiety (d = 0.43). Secondary meta-analyses of 14 studies that conducted partial correlations that controlled for negative affect-related measures revealed that alexithymia was no longer significantly related to pain intensity or interference. Meta-analysis findings demonstrated that alexithymia is elevated in individuals with chronic pain and related to greater pain intensity and physical interference, although the latter relationships may be accounted for by negative affect. Critical future work is needed that examines alexithymia assessed using non-self-report measures, develops a person-centered perspective on this construct, and identifies how alexithymia is relevant to the assessment and treatment of individuals with chronic pain.

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GRK Mediates μ-Opioid Receptor Plasma Membrane Reorganization.

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Behavioral and psychological aspects of cluster headache: an overview.

This paper overviews available literature addressing behavioral and psychological aspects of cluster headache. Behavioral correlates of sleep and drug use are explored, as are the psychological correlates pertaining to psychopathology and cognitive functioning. We conclude with a review of the few investigations addressing adjunctive behavioral treatments for cluster headache, and provide suggestions for possible ways to enhance effects of behavioral interventions for this painful and difficult to treat headache disorder.

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