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Analgesic impact of intra-operative opioids vs. opioid-free anaesthesia: a systematic review and meta-analysis.

Opioids are administered peri-operatively for postoperative analgesia, and intra-operatively to control the sympathetic response to surgical stimuli, frequently as a surrogate for presumed pain. However, opioid use during surgery is a matter of dispute in contemporary practice and carries the risk of side-effects such as postoperative nausea and vomiting. This meta-analysis investigated whether opioid-inclusive, compared with opioid-free anaesthesia, would reduce postoperative pain, without increasing the rate of postoperative nausea and vomiting. The electronic databases Medline and PubMed were searched until June 2018. We included trials investigating pain outcomes and comparing any type of intra-operative opioid administration with placebo injection or no intra-operative opioid. Most meta-analyses were performed using a random effects model. We rated the quality of evidence for each outcome. The primary outcome was pain score at rest (analogue scale, 0-10) at two postoperative hours. Our secondary outcomes included the rate of postoperative nausea and vomiting within the first 24 postoperative hours and length of stay in the recovery area. Twenty-three randomised controlled trials, including 1304 patients, were identified. Pain scores at rest at two postoperative hours were equivalent in the opioid-inclusive and opioid-free groups with a mean difference (95%CI) of 0.2 (-0.2 to 0.5), I = 83%, p = 0.38 and a high quality of evidence. Similarly, there was high-quality evidence that the rate of postoperative nausea and vomiting was reduced in the opioid-free group, with a risk ratio (95%CI) of 0.77 (0.61-0.97), I = 16%, p = 0.03 and high-quality evidence for a similar length of stay in the recovery area, the mean difference (95%CI) being 0.6 (-8.2 to 9.3), min, I = 60%, p = 0.90. As there is strong evidence that opioid-inclusive anaesthesia does not reduce postoperative pain, but is associated with more postoperative nausea and vomiting, when compared with opioid-free anaesthesia, we suggest that anaesthetists should reconsider their intra-operative opioid choices on a case-by-case basis.

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Posttraumatic Stress Symptoms Mediate the Effects of Trauma Exposure on Clinical Indicators of Central Sensitization in Patients With Chronic Pain.

Evidence supports high rates of co-occurrence of posttraumatic stress disorder (PTSD) and chronic pain disorders involving central sensitization (CS). The nature of this relationship, however, remains relatively unexplored. In this study, we aimed to (1) assess how both trauma exposure and current PTSD symptoms are related to clinical manifestations of CS, and (2) test whether PTSD symptoms explain the relationship between trauma exposure and CS. Because experiential avoidance has been shown to impact the relationship between trauma and health outcomes, we (3) explored experiential avoidance as a possible mediator or moderator of the trauma-CS relationship.

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CGRP antagonists in the treatment of episodic migraine.

Migraine is a prevalent, disabling neurological disorder involving the trigeminovascular system. Previous treatments were either originally intended for other conditions and/or associated with intolerable adverse effects. Calcitonin gene-related peptide (CGRP) is the most prevalent neuropeptide in the trigeminal afferent neurons and plays a significant role in pain sensitization central to migraine. The CGRP antagonists (gepants and monoclonal antibodies) are the first treatments created specifically for migraine, modulating pain signaling pathways and alleviating migraine attacks and recurrences. With their efficacy in several clinical trials and relatively fewer adverse effects, the CGRP antagonists show great promise for use in episodic migraine. This article is protected by copyright. All rights reserved.

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Current perspectives on the opioid crisis in the US healthcare system: A comprehensive literature review.

The administration of opioids has been used for centuries as a viable option for pain management. When administered at appropriate doses, opioids prove effective not only at eliminating pain but further preventing its recurrence in long-term recovery scenarios. Physicians have complied with the appropriate management of acute and chronic pain; however, this short or long-term opioid exposure provides opportunities for long-term opioid misuse and abuse, leading to addiction of patients who receive an opioid prescription and/or diversion of this pain medication to other people without prescription. Several reviews attempted to summarize the epidemiology and management of opioid misuse, this integrative review seeks to summarize the current literature related with responsible parties of this opioid abuse crisis and discuss potential associations between demographics (ethnicity, culture, gender, religion) and opioid accessibility, abuse and overdose.

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Towards a neurobiological understanding of pain in neurofibromatosis type 1: mechanisms and implications for treatment.

Neurofibromatosis type 1 (NF1) is the most common of a group of rare diseases known by the term, "Neurofibromatosis," affecting 1 in 3000 to 4000 people. NF1 patients present with, among other disease complications, café au lait patches, skin fold freckling, Lisch nodules, orthopedic complications, cutaneous neurofibromas, malignant peripheral nerve sheath tumors, cognitive impairment, and chronic pain. Although NF1 patients inevitably express pain as a debilitating symptom of the disease, not much is known about its manifestation in the NF1 disease, with most current information coming from sporadic case reports. Although these reports indicate the existence of pain, the molecular signaling underlying this symptom remains underexplored, and thus, we include a synopsis of the literature surrounding NF1 pain studies in 3 animal models: mouse, rat, and miniswine. We also highlight unexplored areas of NF1 pain research. As therapy for NF1 pain remains in various clinical and preclinical stages, we present current treatments available for patients and highlight the importance of future therapeutic development. Equally important, NF1 pain is accompanied by psychological complications in comorbidities with sleep, gastrointestinal complications, and overall quality of life, lending to the importance of investigation into this understudied phenomenon of NF1. In this review, we dissect the presence of pain in NF1 in terms of psychological implication, anatomical presence, and discuss mechanisms underlying the onset and potentiation of NF1 pain to evaluate current therapies and propose implications for treatment of this severely understudied, but prevalent symptom of this rare disease.

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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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