Objective Prolonged exposure to opioids is known to produce neuroplastic changes in animals; however, few studies have investigated the effects of short-term prescription opioid use in humans. A previous study from our laboratory demonstrated a dosage-correlated volumetric decrease in the right amygdala of participants administered oral morphine daily for 1 month. The purpose of this current study was to replicate and extend the initial findings. Methods Twenty-one participants with chronic low back pain were enrolled in this double-blind, placebo-controlled study. Participants were randomized to receive daily morphine (n = 11) or a matched placebo (n = 10) for 1 month. High-resolution anatomical images were acquired immediately before and after the treatment administration period. Morphological gray matter changes were investigated using tensor-based morphometry, and significant regions were subsequently tested for correlation with morphine dosage. Results Decreased gray matter volume was observed in several reward- and pain-related regions in the morphine group, including the bilateral amygdala, left inferior orbitofrontal cortex, and bilateral pre-supplementary motor areas. Morphine administration was also associated with significant gray matter increases in cingulate regions, including the mid cingulate, dorsal anterior cingulate, and ventral posterior cingulate. Conclusions Many of the volumetric increases and decreases overlapped spatially with the previously reported changes. Individuals taking placebo for 1 month showed neither gray matter increases nor decreases. The results corroborate previous reports that rapid alterations occur in reward-related networks following short-term prescription opioid use.

Background: Evidence suggests that neurometabolic abnormalities can persist after traumatic brain injury (TBI) and drive clinical symptoms such as fatigue and cognitive disruption. Magnetic resonance spectroscopy has been used to investigate metabolite abnormalities following TBI, but few studies have obtained data beyond the subacute stage or over large brain regions. Objective: To measure whole-brain metabolites in chronic stages of TBI. Design: Observational study. Setting: University. Participants: Eleven men with a moderate or severe TBI more than 12 months prior and 10 age-matched healthy controls completed whole-brain spectroscopic imaging. Main Measures: Ratios of N-acetylaspartate (NAA), choline (CHO), and myoinositol (MI) to creatine (CR) were measured in whole-brain gray and white matter as well as 64 brain regions of interest. Arterial spin labeling (ASL) data were also collected to investigate whether metabolite abnormalities were accompanied by differences in cerebral perfusion. Results: There were no differences in metabolite ratios within whole-brain gray and white matter regions of interest (ROIs). Linear regression showed lower NAA/CR in the white matter of the left occipital lobe but higher NAA/CR in the gray matter of the left parietal lobe. Metabolite abnormalities were observed in several brain regions in the TBI group including the corpus callosum, putamen, and posterior cingulate. However, none of the findings survived correction for multiple comparison. There were no differences in cerebral blood flow between patients and controls. Conclusion: Higher MI/CR may indicate ongoing gliosis, and it has been suggested that low CHO/CR at chronic time points may indicate cell death or lack of healthy turnover and repair. However, with the small sample size of this study, we caution against the over interpretation of our results. None of the findings within ROIs survived correction for multiple comparison. Thus, they may be considered possible avenues for future research in this area.

Acute administration of donepezil did not significantly improve measures of cognitive or functional ability beyond that of treatment as usual in patients with moderate-to-severe TBI.

OBJECTIVES/SPECIFIC AIMS: In this pilot study, we are testing a new approach for detecting neuroinflammation in individuals who have sustained a traumatic brain injury (TBI). We hypothesize that many long-term adverse consequences of TBI are driven by abnormal inflammatory processes in the brain that occur secondary to the original neural injury. This inflammation can spread well beyond the damaged tissue and cause profound fatigue, widespread pain, cognitive impairment, and depressed mood. METHODS/STUDY POPULATION: Using a technique based on magnetic resonance spectroscopy, we can obtain precise and accurate temperature measurements throughout the human brain, which may serve as a proxy for neuroinflammation. In this study, we examine 20 men who have sustained a moderate-to-severe TBI and 10 age-matched healthy men without history of TBI. Temperature is assessed on a voxel-by-voxel basis throughout the entire brain. Cognitive ability is measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Information on pain, fatigue, and mood is collected through questionnaire. RESULTS/ANTICIPATED RESULTS: We anticipate that (1) average whole-brain temperature will be significantly higher in the TBI group than the healthy control group; (2) severity of (a) pain, (b) fatigue, and (c) mood symptoms will be correlated with brain temperature; and (3) severity of cognitive impairment will be correlated with brain temperature. DISCUSSION/SIGNIFICANCE OF IMPACT: If the hypotheses are confirmed, this tool will fill a need for objective tests of TBI pathology that can be used to improve diagnostic and treatment decisions and predict long-term functioning. This test would be the first completely noninvasive tool for detecting neuroinflammation, and will allow for safe and inexpensive longitudinal testing. Ultimately, we hope this noninvasive scanning technique will accurately track neuroinflammation in TBI, leading to more targeted and effective treatments.

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