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Assessment of Changes in the Geographical Distribution of Opioid-Related Mortality Across the United States by Opioid Type, 1999-2016.

As the opioid epidemic evolves, it is vital to identify changes in the geographical distribution of opioid-related deaths, and the specific opioids to which those deaths are attributed, to ensure that federal and state public health interventions remain appropriately targeted.

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Social representations of chronic pain in newspapers, online media, and film.

Social representation theory provides a framework for studying how scientific knowledge affects common sense and communication through inquiries into everyday discourse. This qualitative study examined social representations of chronic pain from 4 sources: North American newspapers; "Chronic Illness Cat" memes from the social media web site, Pinterest; video blogs on YouTube; and from a 2014 film, Cake, and interviews and comments concerning it. Using thematic analysis, we first identified social representations found in our 4 sources and others found in 1 or 2 of them. Second, we analyzed the sources for their rhetorical intentions. Vlogs directly and memes indirectly were first-person accounts, self-authorizing statements of the truth of chronic pain, whereas newspaper articles and the film were third-person accounts of pain, the differences between these perspectives affecting what was said. We conclude that the medium shapes the message.

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Attentional, interpretation and memory biases for sensory-pain words in individuals with chronic headache.

Cognitive biases in attention, interpretation and less consistently memory have been observed in individuals with chronic pain and play a critical role in the onset and maintenance of chronic pain. Despite operating in combination cognitive biases are typically explored in isolation.

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Potentially Unsafe Chronic Medication Use among Older Adult Chronic Opioid Users.

To assess chronic potentially unsafe medication use among older adults using opioids chronically versus those who did not, to assess the likelihood of chronically using medications to treat adverse effects associated with chronic opioid use, and to characterize the differences in chronic potentially unsafe medication use at three morphine equivalent dose (MED) levels/day (<50MED, 50-90MED, and >90MED).

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Prevention of Prescription Opioid Misuse and Projected Overdose Deaths in the United States.

Deaths due to opioid overdose have tripled in the last decade. Efforts to curb this trend have focused on restricting the prescription opioid supply; however, the near-term effects of such efforts are unknown.

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Testing the exteroceptive function of nociception: the role of visual experience in shaping the spatial representations of nociceptive inputs.

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Neural indicators of perceptual variability of pain across species.

Individuals exhibit considerable and unpredictable variability in painful percepts in response to the same nociceptive stimulus. Previous work has found neural responses that, while not necessarily responsible for the painful percepts themselves, can still correlate well with intensity of pain perception within a given individual. However, there is no reliable neural response reflecting the variability in pain perception across individuals. Here, we use an electrophysiological approach in humans and rodents to demonstrate that brain oscillations in the gamma band [gamma-band event-related synchronization (γ-ERS)] sampled by central electrodes reliably predict pain sensitivity across individuals. We observed a clear dissociation between the large number of neural measures that reflected subjective pain ratings at within-subject level but not across individuals, and γ-ERS, which reliably distinguished subjective ratings within the same individual but also coded pain sensitivity across different individuals. Importantly, the ability of γ-ERS to track pain sensitivity across individuals was selective because it did not track the between-subject reported intensity of nonpainful but equally salient auditory, visual, and nonnociceptive somatosensory stimuli. These results also demonstrate that graded neural activity related to within-subject variability should be minimized to accurately investigate the relationship between nociceptive-evoked neural activities and pain sensitivity across individuals.

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Pills to Pot: Observational Analyses of Cannabis Substitution Among Medical Cannabis Users With Chronic Pain.

Chronic pain is common, costly, and challenging to treat. Many individuals with chronic pain have turned to cannabis as an alternative form of pain management. We report results from an ongoing, online survey of medical cannabis users with chronic pain nationwide about how cannabis affects pain management, health, and pain medication use. We also examined whether and how these parameters were affected by concomitant recreational use, and duration of use (novice: <1 year vs experienced: ≥1 year). There were 1,321 participants (59% female, 54% ≥50 years old) who completed the survey. Consistent with other observational studies, approximately 80% reported substituting cannabis for traditional pain medications (53% for opioids, 22% for benzodiazepines), citing fewer side effects and better symptom management as their rationale for doing so. Medical-only users were older (52 vs 47 years old; P < .0001), less likely to drink alcohol (66% vs 79%, P < .0001), and more likely to be currently taking opioids (21% vs 11%, P < .0001) than users with a combined recreational and medical history. Compared with novice users, experienced users were more likely to be male (64% vs 58%; P < .0001), take no concomitant pain medications (43% vs 30%), and report improved health (74% vs 67%; P = .004) with use. Given that chronic pain is the most common reason for obtaining a medical cannabis license, these results highlight clinically important differences among the changing population of medical cannabis users. More research is needed to better understand effective pain management regimens for medical cannabis users. Perspective: This article presents results that confirm previous clinical studies suggesting that cannabis may be an effective analgesic and potential opioid substitute. Participants reported improved pain, health, and fewer side effects as rationale for substituting. This article highlights how use duration and intentions for use affect reported treatment and substitution effects.

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Genomic, Ancestral and Networking Analyses of a High-Altitude Native American Ecuadorian Patient with Congenital Insensitivity to Pain with Anhidrosis.

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Characterization of drug binding within the HCN1 channel pore.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels mediate rhythmic electrical activity of cardiac pacemaker cells, and in neurons play important roles in setting resting membrane potentials, dendritic integration, neuronal pacemaking, and establishing action potential threshold. Block of HCN channels slows the heart rate and is currently used to treat angina. However, HCN block also provides a promising approach to the treatment of neuronal disorders including epilepsy and neuropathic pain. While several molecules that block HCN channels have been identified, including clonidine and its derivative alinidine, lidocaine, mepivacaine, bupivacaine, ZD7288, ivabradine, zatebradine, and cilobradine, their low affinity and lack of specificity prevents wide-spread use. Different studies suggest that the binding sites of these inhibitors are located in the inner vestibule of HCN channels, but the molecular details of their binding remain unknown. We used computational docking experiments to assess the binding sites and mode of binding of these inhibitors against the recently solved atomic structure of human HCN1 channels, and a homology model of the open pore derived from a closely related CNG channel. We identify a possible hydrophobic groove in the pore cavity that plays an important role in conformationally restricting the location and orientation of drugs bound to the inner vestibule. Our results also help explain the molecular basis of the low-affinity binding of these inhibitors, paving the way for the development of higher affinity molecules.

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