Dataset Information

Defining and Managing Pain in Stroke and Traumatic Brain Injury Research.

ABSTRACT: Neurologic conditions such as stroke and traumatic brain injury are challenging conditions to study in humans. Animal models are necessary to uncover disease processes and develop novel therapies. When attempting to model these or other neurologic diseases, the accompanying anesthesia and analgesia create variables that are not part of the onset of the clinical disease in the human population but are critical components of the postinjury care both in humans and animals. To maximize model validity, researchers must consider whether the disease process or a novel therapy is being studied. Damage to the neurons of the brain or the spinal cord is not painful at the neural tissue itself, but alterations to nociceptive signaling along the pain pathway can induce chronic pain. In addition, trauma or surgery leading to the event is associated with damage to peripheral tissue. Inflammation is inextricably associated with tissue injury. Inflammation is known to evoke nociception in the periphery and drive long-term changes to neurons in the CNS. Analgesics and anesthetics alter these responses yet are required as part of humane animal care. Careful planning for effective drug administration consistent with the standard of care for humans and equivalent animal care is required.

SUBMITTER: Larson CM

PROVIDER: S-EPMC6935700 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Defining and Managing Pain in Stroke and Traumatic Brain Injury Research.

Larson Christina M CM Wilcox George L GL Fairbanks Carolyn A CA

Comparative medicine 20191220 6

Neurologic conditions such as stroke and traumatic brain injury are challenging conditions to study in humans. Animal models are necessary to uncover disease processes and develop novel therapies. When attempting to model these or other neurologic diseases, the accompanying anesthesia and analgesia create variables that are not part of the onset of the clinical disease in the human population but are critical components of the postinjury care both in humans and animals. To maximize model validit ...[more]

PMID: 31896392

Similar Datasets

Project description:Traumatic brain injury (TBI) can lead to a variety of comorbidities, including chronic pain. Although brain tissue metabolite alterations have been extensively examined in several chronic pain populations, it has received less attention in people with TBI. Thus, the primary aim of this study was to compare brain tissue metabolite levels in people with TBI and chronic pain (n = 16), TBI without chronic pain (n = 17), and pain-free healthy controls (n = 31). The metabolite data were obtained from participants using whole-brain proton magnetic resonance spectroscopic imaging (1H-MRSI) at 3 Tesla. The metabolite data included N-acetylaspartate, myo-inositol, total choline, glutamate plus glutamine, and total creatine. Associations between N-acetylaspartate levels and pain severity, neuropathic pain symptom severity, and psychological variables, including anxiety, depression, post-traumatic stress disorder (PTSD), and post-concussive symptoms, were also explored. Our results demonstrate N-acetylaspartate, myo-inositol, total choline, and total creatine alterations in pain-related brain regions such as the frontal region, cingulum, postcentral gyrus, and thalamus in individuals with TBI with and without chronic pain. Additionally, NAA levels in the left and right frontal lobe regions were positively correlated with post-concussive symptoms; and NAA levels within the left frontal region were also positively correlated with neuropathic pain symptom severity, depression, and PTSD symptoms in the TBI with chronic pain group. These results suggest that neuronal integrity or density in the prefrontal cortex, a critical region for nociception and pain modulation, is associated with the severity of neuropathic pain symptoms and psychological comorbidities following TBI. Our data suggest that a combination of neuronal loss or dysfunction and maladaptive neuroplasticity may contribute to the development of persistent pain following TBI, although no causal relationship can be determined based on these data.

Project description:Traumatic brain injury (TBI) is the most common cause of death and disability in the age group below 40 years. The financial cost of loss of earnings and medical care presents a massive burden to family, society, social care, and healthcare, the cost of which is estimated at £1 billion per annum (about brain injury (online)). At present, we still lack a full understanding on the pathophysiology of TBI, and biomarkers represent the next frontier of breakthrough discoveries. Unfortunately, many tenets limit their widespread adoption. Brain tissue sampling is the mainstay of diagnosis in neuro-oncology; following on this path, we hypothesise that information gleaned from neural tissue samples obtained in TBI patients upon hospital admission may correlate with outcome data in TBI patients, enabling an early, accurate, and more comprehensive pathological classification, with the intent of guiding treatment and future research. We proposed various methods of tissue sampling at opportunistic times: two methods rely on a dedicated sample being taken; the remainder relies on tissue that would otherwise be discarded. To gauge acceptance of this, and as per the guidelines set out by the National Research Ethics Service, we conducted a survey of TBI and non-TBI patients admitted to our Trauma ward and their families. 100 responses were collected between December 2017 and July 2018, incorporating two redesigns in response to patient feedback. 75.0% of respondents said that they would consent to a brain biopsy performed at the time of insertion of an intracranial pressure (ICP) bolt. 7.0% replied negatively and 18.0% did not know. 70.0% would consent to insertion of a jugular bulb catheter to obtain paired intracranial venous samples and peripheral samples for analysis of biomarkers. Over 94.0% would consent to neural tissue from ICP probes, external ventricular drains (EVD), and lumbar drains (LD) to be salvaged, and 95.0% would consent to intraoperative samples for further analysis.

Project description:Pressure reactivity index (PRx) and brain tissue oxygen (PbtO2) are associated with outcome in traumatic brain injury (TBI). This study explores the relationship between PRx and PbtO2 in adult moderate/severe TBI. Using the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high resolution intensive care unit (ICU) sub-study cohort, we evaluated those patients with archived high-frequency digital intraparenchymal intracranial pressure (ICP) and PbtO2 monitoring data of, a minimum of 6 h in duration, and the presence of a 6 month Glasgow Outcome Scale -Extended (GOSE) score. Digital physiological signals were processed for ICP, PbtO2, and PRx, with the % time above/below defined thresholds determined. The duration of ICP, PbtO2, and PRx derangements was characterized. Associations with dichotomized 6-month GOSE (alive/dead, and favorable/unfavorable outcome; ≤ 4 = unfavorable), were assessed. A total of 43 patients were included. Severely impaired cerebrovascular reactivity was seen during elevated ICP and low PbtO2 episodes. However, most of the acute ICU physiological derangements were impaired cerebrovascular reactivity, not ICP elevations or low PbtO2 episodes. Low PbtO2 without PRx impairment was rarely seen. % time spent above PRx threshold was associated with mortality at 6 months for thresholds of 0 (area under the curve [AUC] 0.734, p = 0.003), > +0.25 (AUC 0.747, p = 0.002) and > +0.35 (AUC 0.745, p = 0.002). Similar relationships were not seen for % time with ICP >20 mm Hg, and PbtO2 < 20 mm Hg in this cohort. Extreme impairment in cerebrovascular reactivity is seen during concurrent episodes of elevated ICP and low PbtO2. However, the majority of the deranged cerebral physiology seen during the acute ICU phase is impairment in cerebrovascular reactivity, with most impairment occurring in the presence of normal PbtO2 levels. Measures of cerebrovascular reactivity appear to display the most consistent associations with global outcome in TBI, compared with ICP and PbtO2.

Dataset Information

Defining and Managing Pain in Stroke and Traumatic Brain Injury Research.

Publications

Defining and Managing Pain in Stroke and Traumatic Brain Injury Research.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets