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Remifentanil for abdominal surgery is associated unexpectedly unfavorable outcomes.

Insufficient perioperative pain treatment is known as a highly predictive risk factor for the development of chronic postoperative pain. Remifentanil is an ultrashort-acting opioid that provides quick and efficient analgesia but is associated with the induction of opioid-induced hyperalgesia. Despite these well-known characteristics, this substance is being increasingly used in anesthesia and in a variety of medical fields, such as intensive-care medicine and obstetrics.The aim of our study was to reveal whether remifentanil influences postoperative pain, the requirement for postoperative analgesics, and requirement of antiemetics (as indirect indicator of postoperative nausea and vomiting (PONV), as well as the effects on time to extubation and length of stay in the postanesthesia care-unit (PACU) in daily clinical routine.From an electronic medical records database of 55,693 anesthesias, we analyzed data from all patients receiving intraabdominal surgery (visceral, gynecological and urological) under general anesthesia or combined general-epidural anesthesia by propensity score matching.The administration of remifentanil was associated with higher postoperative pain scores despite a higher requirement of postoperative analgesics. Additional epidural analgesia was not able to avoid this finding.The intraoperative use of remifentanil is associated with a deterioration of pain levels and postoperative analgesic requirement, wherefore the potential benefit of this substance seems to be outweighed by its potential disadvantages. Especially in operative procedures in which high postoperative pain scores are expected, the unreflective use should be critically questioned.

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Pain, Anxiety, and Depression in the First Two Years Following Transport-Related Major Trauma: A Population-Based, Prospective Registry Cohort Study.

This study aimed to characterize the population prevalence of pain and mental health problems postinjury and to identify risk factors that could improve service delivery to optimize recovery of at-risk patients.

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Cannabis Use and Cognition in Adults Prescribed Opioids for Persistent Pain.

Adults with persistent pain frequently report cannabis use to help manage their symptoms. The impact of cannabis use on cognition in the presence of concurrent symptoms of depression and anxiety is poorly understood.

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Globotriaosylceramide-induced reduction of K1.1 channel activity and activation of the Notch1 signaling pathway in skin fibroblasts of male Fabry patients with pain.

Fabry disease (FD) is an X-linked lysosomal storage disorder that leads to cellular globotriaosylceramide (Gb3) accumulation due to mutations in the gene encoding α-galactosidase A. Trigger-induced acral burning pain is an early FD symptom of unknown pathophysiology. We aimed at investigating the potential role of skin fibroblasts in nociceptor sensitization.

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A safe bet? Inter-laboratory variability in behaviour-based severity assessment.

Evidence-based severity assessment is essential as a basis for ethical evaluation in animal experimentation to ensure animal welfare, legal compliance and scientific quality. To fulfil these tasks scientists, animal care and veterinary personnel need assessment tools that provide species-relevant measurements of the animals' physical and affective state. In a three-centre study inter-laboratory robustness of body weight monitoring, mouse grimace scale (MGS) and burrowing test were evaluated. The parameters were assessed in naïve and tramadol treated female C57BL/6J mice. During tramadol treatment a body weight loss followed by an increase, when treatment was terminated, was observed in all laboratories. Tramadol treatment did not affect the MGS or burrowing performance. Results were qualitatively comparable between the laboratories, but quantitatively significantly different (inter-laboratory analysis). Burrowing behaviour seems to be highly sensitive to inter-laboratory differences in testing protocol. All locations obtained comparable information regarding the qualitative effect of tramadol treatment in C57BL/6J mice, however, datasets differed as a result of differences in test and housing conditions. In conclusion, our study confirms that results of behavioural testing can be affected by many factors and may differ between laboratories. Nevertheless, the evaluated parameters appeared relatively robust even when conditions were not harmonized extensively and present useful tools for severity assessment. However, analgesia-related side effects on parameters have to be considered carefully.

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Interhemispheric transfer of post-amputation cortical plasticity within the human somatosensory cortex.

Animal models reveal that deafferenting forelimb injuries precipitate reorganization in both contralateral and ipsilateral somatosensory cortices. The functional significance and duration of these effects are unknown, and it is unclear whether they also occur in injured humans. We delivered cutaneous stimulation during functional magnetic resonance imaging (fMRI) to map the sensory cortical representation of the intact hand and lower face in a group of chronic, unilateral, upper extremity amputees (N = 19) and healthy matched controls (N = 29). Amputees exhibited greater activity than controls within the deafferented former sensory hand territory (S1f) during stimulation of the intact hand, but not of the lower face. Despite this cortical reorganization, amputees did not differ from controls in tactile acuity on their intact hands. S1f responses during hand stimulation were unrelated to tactile acuity, pain, prosthesis usage, or time since amputation. These effects appeared specific to the deafferented somatosensory modality, as fMRI visual mapping paradigm failed to detect any differences between groups. We conclude that S1f becomes responsive to cutaneous stimulation of the intact hand of amputees, and that this modality-specific reorganizational change persists for many years, if not indefinitely. The functional relevance of these changes, if any, remains unknown.

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Systematic Review of Pain Severity and Opioid Craving in Chronic Pain and Opioid Use Disorder.

To evaluate measurement and associations between pain severity and opioid craving in individuals with chronic pain on long-term opioid therapy and/or with opioid use disorder.

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Congenital insensitivity to pain with anhidrosis syndrome: A series from Jordan.

To present the clinical picture, the associated complications and the genetic findings of Jordanian patients diagnosed with Congenital insensitivity to pain with anhidrosis (CIPA).

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Early Treatment With Metformin in a Mice Model of Complex Regional Pain Syndrome Reduces Pain and Edema.

Metformin, an adenosine monophosphate (AMP)-activated protein kinase activator, as well as a common drug for type 2 diabetes, has previously been shown to decrease mechanical allodynia in mice with neuropathic pain. The objective of this study is to determine if treatment with metformin during the first 3 weeks after fracture would produce a long-term decrease in mechanical allodynia and improve a complex behavioral task (burrowing) in a mouse tibia fracture model with signs of complex regional pain syndrome.

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Reversal of peripheral nerve injury-induced neuropathic pain and cognitive dysfunction via genetic and tomivosertib targeting of MNK.

Neuropathic pain caused by nerve injury presents with severe spontaneous pain and a variety of comorbidities, including deficits in higher executive functions. None of these clinical problems are adequately treated with current analgesics. Targeting of the mitogen-activated protein kinase-interacting kinase (MNK1/2) and its phosphorylation target, the mRNA cap binding protein eIF4E, attenuates many types of nociceptive plasticity induced by inflammatory mediators and chemotherapeutic drugs but inhibiting this pathway does not alter nerve injury-induced mechanical allodynia. We used genetic manipulations and pharmacology to inhibit MNK-eIF4E activity in animals with spared nerve injury, a model of peripheral nerve injury (PNI)-induced neuropathic pain. We assessed the presence of spontaneous pain using conditioned place preference. We also tested performance in a medial prefrontal cortex (mPFC)-dependent rule-shifting task. WT neuropathic animals showed signs of spontaneous pain and were significantly impaired in the rule-shifting task while genetic and pharmacological inhibition of the MNK-eIF4E signaling axis protected against and reversed spontaneous pain and PNI-mediated cognitive impairment. Additionally, pharmacological and genetic inhibition of MNK-eIF4E signaling completely blocked and reversed maladaptive shortening in the length of axon initial segments (AIS) in the mPFC of PNI mice. Surprisingly, these striking positive outcomes on neuropathic pain occurred in the absence of any effect on mechanical allodynia, a standard test for neuropathic pain efficacy. Our results illustrate new testing paradigms for determining preclinical neuropathic pain efficacy and point to the MNK inhibitor tomivosertib (eFT508) as an important drug candidate for neuropathic pain treatment.

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