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Primary headaches during lifespan.

Primary headaches are one of the most prevalent neurological disorders and can occur during a wide range of lifespan. Primary headaches, especially migraine, are cyclic disorders with a complex sequence of symptoms within every headache attack. There is no systematic review of whether these symptoms changes during lifespan. Indeed, the clinical presentation of migraine shows an age-dependent change with a significantly shorter duration of the attacks and occurrence of different paroxysmal symptoms, such as vomiting, abdominal pain or vertigo, in childhood and, in contrast, largely an absence of autonomic signs and a more often bilateral headache in the elderly. The age-dependent differences in the clinical presentation are less distinct in cluster headache and, especially, in tension-type headache. The differences in the clinical presentation are in agreement with the idea that the connectivity of hypothalamic areas with different brainstem areas, especially the central parasympathetic areas, is important for the clinical manifestation of migraine, as well as, the change during lifespan.

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Migraine and episodic Vertigo: a cohort survey study of their relationship.

Migraine headache and vestibular-type vertigo co-occur in the general population about three times more often than expected by chance. Attacks of episodic vertigo (eV) are currently not recognized as migraine equivalents or variants in the International Classification of Headache Disorders, 3rd edition (ICHD III). No strong data exist about the prevalence of eV during the phases of a migraine attack. The aim of this study is to analyze the timing association between migraine-related episodic vertigo and the phases of migraine.

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Cognitive self-regulation influences pain-related physiology.

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Somatosensory predictors of response to pregabalin in painful chemotherapy-induced peripheral neuropathy: a randomized, placebo-controlled, crossover study.

Painful chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and treatment-resistant sequela of many chemotherapeutic medications. Ligands of α2δ subunits of voltage-gated Ca channels, such as pregabalin, have shown efficacy in reducing mechanical sensitivity in animal models of neuropathic pain. In addition, some data suggest that pregabalin may be more efficacious in relieving neuropathic pain in subjects with increased sensitivity to pinprick. We hypothesized that greater mechanical sensitivity, as quantified by decreased mechanical pain threshold (MPT) at the feet, would be predictive of a greater reduction in average daily pain in response to pregabalin versus placebo. In a prospective, randomized, double-blinded study, 26 patients with painful CIPN from oxaliplatin, docetaxel, or paclitaxel received 28-day treatment with pregabalin (titrated to maximum dose 600 mg per day) and placebo in cross-over design. Twenty-three participants were eligible for efficacy analysis. MPT was not significantly correlated with reduction in average pain (P = 0.97) or worst pain (P = 0.60) in response to pregabalin. There was no significant difference between pregabalin and placebo in reducing average daily pain (22.5% vs 10.7%, P = 0.23) or worst pain (29.2% vs 16.0%, P = 0.13) from baseline. Post-hoc analysis of patients with CIPN caused by oxaliplatin (n = 18) demonstrated a larger reduction in worst pain with pregabalin than with placebo (35.4% versus 14.6%, P = 0.04). In summary, baseline MPT tested on dorsal feet did not meaningfully predict the analgesic response to pregabalin in painful CIPN.

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Remembering the pain of surgery one year later: a longitudinal examination of anxiety in children’s pain memory development.

Children who develop greater negatively biased recall of pain (i.e., recalled pain is higher than the initial pain report) following surgery are at risk for developing chronic pain; therefore, identifying risk factors for the development of biased pain memories is important. Higher anxiety has been implicated in the development of greater negatively biased recall of pain; however, studies have not examined anxiety at multiple time points before and after a surgery and its relationship to children's post-surgical pain memories after one year. This prospective study examined a cohort of 237 children and adolescents undergoing major surgery. Anxiety sensitivity, pain catastrophizing, and pain anxiety were assessed at baseline, 48-72 hours post-surgery, and at 6- and 12-month follow-ups. Pain intensity at rest, movement-evoked pain intensity, and pain unpleasantness were assessed daily in hospital. Memories for pain were elicited via telephone one-year post surgery. Findings revealed that children who had higher levels of anxiety at baseline and 48-72 hours post-surgery developed greater negatively biased recall of pain intensity 12 months after surgery. Specifically, higher anxiety sensitivity at baseline and greater tendencies to catastrophize about pain at baseline and in the immediate acute recovery phase were most strongly linked to greater negatively biased recall of pain. Greater negatively biased recall of pain was related to higher pain intensity at 6- and 12-months post-surgery. Findings support conceptual models of anxiety and pain memory biases and can inform intervention efforts to reduce anxiety in the pre- and post-op periods to minimize negative biases in pain memories.

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Cortisol affects pain sensitivity and pain-related emotional learning in experimental visceral but not somatic pain: A randomized-controlled study in healthy men and women.

Despite growing interest in the role of stress mediators in pain chronicity, the effects of the stress hormone cortisol on acute pain remain incompletely understood. In a randomized, double-blind, placebo-controlled study with N=100 healthy volunteers, we tested the effects of oral hydrocortisone (20 mg) in two widely-used pain models for the visceral and somatic modality.Salivary cortisol was increased in the hydrocortisone group (time x group: p<.001). For the visceral modality, assessed using pressure-controlled rectal distensions, hydrocortisone decreased the pain threshold from pre- to post-treatment (time x group: p=.011), an effect primarily driven by women (time x sex: p=.027). For the somatic modality, cutaneous heat pain thresholds remained unaffected by hydrocortisone. Hydrocortisone did not alter perceived pain intensity or unpleasantness of either modality. Conditioned pain-related fear in response to predictive cues was only observed for the visceral modality (time x modality: p=.026), an effect that was significantly reduced by hydrocortisone compared ot placebo (time x group: p=.028).This is the first psychopharmacological study to support that acutely increased cortisol enhances pain sensitivity and impairs pain-related emotional learning within the visceral, but not the somatic pain modality. Stress-induced visceral hyperalgesia and deficits in emotional pain-related learning could play a role in the pathophysiology of chronic visceral pain.

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The efficacy of a transdiagnostic emotion-focused exposure treatment for chronic pain patients with comorbid anxiety and depression: a randomized controlled trial.

The comorbidity between chronic pain and emotional problems has proven difficult to address with current treatment options. This study addresses the efficacy of a transdiagnostic emotion focused exposure treatment ("hybrid") for chronic pain patients with comorbid emotional problems. Adults (n=115) with chronic musculoskeletal pain, functional and emotional problems were included in a two centre, parallel randomized controlled, open label trial comparing this treatment to an active control condition receiving a guided internet delivered pain management treatment based on CBT principles (iCBT). The hybrid treatment (n=58, 10-16 sessions) integrates exposure in vivo for chronic pain based on the fear-avoidance model with an emotion regulation approach informed by procedures in Dialectical Behavior Therapy. The iCBT (n=57; 8 treatment modules) addresses topics such as pain education, coping strategies, relaxation, problem solving, stress and sleep management using standard CBT techniques. Patient-reported outcomes were assessed pre- and posttreatment as well as at a 9-month primary end point. Across conditions, 78% participants completed post-treatment and 81% follow-up assessment. Intent-to-treat analyses showed that the hybrid had a significantly better post-treatment outcome on pain catastrophizing (d=0.39) and pain interference (d=0.63) and significantly better follow-up outcomes on depression (d=0.43) and pain interference (d=0.51). There were no differences on anxiety and pain intensity. Observed proportions of clinically significant improvement favoured the hybrid on all but one comparison, but no statistically significant differences were observed. We conclude that the hybrid emotion focused treatment may be considered an acceptable, credible and efficacious treatment option for chronic pain patients with comorbid emotional problems.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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The combination of opioid and neurotensin receptor agonists improves their analgesic/adverse effect ratio.

Opioid and neurotensin (NT) receptors are expressed in both central and peripheral nervous systems where they modulate nociceptive responses. Nowadays, opioid analgesics like morphine remain the most prescribed drugs for the treatment of moderate to severe pain. However, despite their daily used, opioids can produce life-threatening side effects, such as constipation or respiratory depression. Besides, NT analogs exert strong opioid-independent analgesia. Here, we thus hypothesized that the combined use of opioid and NT agonists would require lower doses to produce significant analgesic effects, hence decreasing opioid-induced adverse effects. We used isobologram analyses to determine if the combination of a NT brain-penetrant analog, An2-NT(8-13) with morphine results in an inhibitory, synergistic or additive analgesic response. We found that intravenous administration of An2-NT(8-13) reduced by 90% the nocifensive behaviors induced by formalin injection, at the dose of 0.018mg/kg. Likewise, subcutaneous morphine reduced pain by 90% at 1.8mg/kg. Importantly, isobologram analyses revealed that the co-injection of An2-NT(8-13) with morphine induced an additive analgesic response. We finally assessed the effects of morphine and An2-NT(8-13) on the gastrointestinal tract motility using the charcoal meal test. As opposed to morphine which significantly reduced the intestinal motility at the analgesic effective dose of 1.8mg/kg, An2-NT(8-13) did not affect the charcoal meal intestinal transit at 0.018mg/kg. Interestingly, at the dose providing 90% pain relief, the co-administration of morphine with An2-NT(8-13) had a reduced effect on constipation. Altogether, these results suggest that combining NT agonists with morphine may improve its analgesic/adverse effect ratio.

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Association Between Opioid Dose Variability and Opioid Overdose Among Adults Prescribed Long-term Opioid Therapy.

Attempts to discontinue opioid therapy to reduce the risk of overdose and adhere to prescribing guidelines may lead patients to be exposed to variability in opioid dosing. Such dose variability may increase the risk of opioid overdose even if therapy discontinuation is associated with a reduction in risk.

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Within-finger maps of tactile and nociceptive input in the human parietal cortex.

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