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Pain is the primary symptom of chronic pancreatitis (CP), but methods for sensory testing and pain characterization have not previously been validated for clinical use. We present a clinically feasible method for the assessment and characterization of pain mechanisms in patients with CP based on quantitative sensory testing (QST).
Learn More >This updated systematic review evaluated the efficacy, tolerability and safety of opioids compared to placebo in chronic non-cancer neuropathic pain.
Learn More >Opioids are commonly used to provide analgesia for cancer pain, and functional opioid receptors have been identified on natural killer (NK) cells, the lymphocytes responsible for surveillance and elimination of cancer cells. Opioids also bind to other lymphocyte receptors, such as Toll-like receptor (TLR)-4. Here, we characterized the effects of morphine on primary human NK cell cytotoxicity and mediator release, which occur through classical opioid receptor or TLR4 signaling.
Learn More >The trigeminal nerve (TGN) is the largest cranial nerve and can be involved in multiple inflammatory, compressive, ischemic or other pathologies. Currently, imaging-based approaches to identify the TGN mostly rely on T2-weighted magnetic resonance imaging (MRI), which provides localization of the cisternal portion of the TGN where the contrast between nerve and cerebrospinal fluid (CSF) is high enough to allow differentiation. The course of the TGN within the brainstem as well as anterior to the cisternal portion, however, is more difficult to display on traditional imaging sequences. An advanced imaging technique, diffusion MRI (dMRI), enables tracking of the trajectory of TGN fibers and has the potential to visualize anatomical regions of the TGN not seen on T2-weighted imaging. This may allow a more comprehensive assessment of the nerve in the context of pathology. To date, most work in TGN tracking has used clinical dMRI acquisitions with a b-value of 1000 s/mm and conventional diffusion tensor MRI (DTI) tractography methods. Though higher b-value acquisitions and multi-tensor tractography methods are known to be beneficial for tracking brain white matter fiber tracts, there have been no studies conducted to evaluate the performance of these advanced approaches on nerve tracking of the TGN, in particular on tracking different anatomical regions of the TGN.
Learn More >Migraine is recognized as a neurological condition that is often associated with comorbid psychiatric symptoms such as anxiety, depression, bipolar disorder and/or panic disorder. Though some studies have demonstrated the link between migraine and anxiety disorders, there are no systematic reviews that have been published in this area to summarize the evidence. The aim of the present study is to systematically review the literature associated with comorbidity of migraine and anxiety disorders among migraineurs compared to non-migraineurs. The present systematic review included population-based, cohort and cross-sectional studies if they were reporting the frequency of migraine with either anxiety or depression as diagnosed by a medical practitioner according to the International Classification of Headache Disorders (ICHD-2/3). Eight eligible studies from 2060 relevant citations were included in the review. All participants were migraine patients from both primary care and outpatient settings, as well as tertiary headache and anxiety centers, and were compared to non-migraineurs. The results of the systematic review showed that there is a strong and consistent relationship between migraine and anxiety. The co-morbidity of co-occurrence for migraine and anxiety has an average OR of 2.33 (2.20-2.47) among the prevalence and cross sectional studies and an average RR of 1.63 (1.37-1.93) for two cohort studies; The major limitations of included studies were small sample sizes and a lack of adjusting of confounding factors. The results highlight the need for inclusion of an anxiety screening tool during initial assessments of migraine patients by medical practitioners and/or physicians and may explain why some anxiolytic medications work better than others for migraine mitigation.
Learn More >Chronic pain is prevalent in idiopathic Parkinson's disease (PD) with many individuals also experiencing cognitive deficits negatively impacting everyday life.
Learn More >Orofacial pain features may negatively influence a person's well-being and vice versa. Some aspects of well-being can be measured with axis II instruments that assess patients' psychosocial and behavioral status. The aim of this study was to investigate associations between pain features and psychosocial variables as indicators of well-being. Seven hundred ninety-nine anonymized datasets collected using the Web-based Interdisciplinary Symptom Evaluation (WISE) of patients reporting to the Interdisciplinary Orofacial Pain Unit, University of Zurich, between March 19, 2017 and May 19, 2019, were analyzed. Pain features including intensity, number of locations, impact, and duration were evaluated. Psychometric measures assessed pain-related catastrophizing and disability, illness perception, distress, anxiety, depression, injustice experience, dysmorphic concerns, and insomnia. Most patients were between 30 and 59 years old (58.3%), female (69.8%), working (66.0%), and experienced pain for more than 6 months (68.5%). Pain intensities were higher in women than men and higher in disabled than working patients. Scores indicating elevated stress and depression were also observed in disabled patients. The sample prevalence rates of clinically relevant axis II instrument scores were as follows: Graded Chronic Pain Scale for the Head (GCPS-H), 27%; Patient Health Questionnaire 4 (PHQ4), 21%; PHQ9, 21%; Pain Catastrophizing Scale (PCS), 20%; General Anxiety Disorder 7 (GAD7), 15%; Insomnia Severity Index (ISI), 15%; Injustice Experience Questionnaire (IEQ), 14%; GCPS for the Body (GCPS-B), 13%; PHQ for Stress (PHQstr), 6%; and Dysmorphic Concern Questionnaire (DCQ), 2%. Noteworthy results of correlation analysis of the clinically relevant axis II scores and pain measures were as follows: the PHQstr had moderate associations (0.34-0.43) with the sum of pain intensity at rest and during function, number of pain locations, and typical pain intensity. The IEQ scores were moderately associated with typical pain intensity at 0.39. The DCQ scores were moderately associated with pain extension at 0.41. Moderate correlations of certain pain and well-being measures were found in patients reporting clinically relevant stress, injustice experience, and dysmorphic concern, all of which reflect impaired well-being. PHQ4 is suitable for routine distress screening in the clinical setting.
Learn More >Reported pain intensity depends not only on stimulus intensity but also on previously experienced pain. A painfully hot temperature applied to the skin evokes a lower subjective pain intensity if immediately preceded by a higher temperature, a phenomenon called offset analgesia. Previous work indicated that prior pain experience can also increase subsequent perceived pain intensity. Therefore, we examined whether a given noxious stimulus is experienced as more intense when it is preceded by an increase from a lower temperature. Using healthy volunteer subjects, we observed a disproportionate increase in pain intensity at a given stimulus intensity when this intensity is preceded by a rise from a lower intensity. This disproportionate increase is similar in magnitude to that of offset analgesia. We call this effect onset hyperalgesia. Control stimuli, in which a noxious temperature is held constant, demonstrate that onset hyperalgesia is distinct from receptor or central sensitization. The absolute magnitudes of offset analgesia and onset hyperalgesia correlate with each other but not with the noxious stimulus temperature. Finally, the magnitude of both offset analgesia and onset hyperalgesia depends on preceding temperature changes. Overall, this study demonstrates that the perceptual effect of a noxious thermal stimulus is influenced in a bidirectional manner depending upon both the intensity and direction of change of the immediately preceding thermal stimulus.
Learn More >Preoperative patient-specific risk factors may elucidate the mechanisms leading to the persistence of pain and opioid use after surgery. This study aimed to determine whether similar or discordant preoperative factors were associated with the duration of postoperative pain and opioid use.
Learn More >Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent, painful side effect which arises due to a number of chemotherapy agents. CIPN can have a prolonged effect on quality of life. Chemotherapy treatment is often reduced or stopped altogether because of the severe pain. Currently, there are no FDA-approved treatments for CIPN partially due to its complex pathogenesis in multiple pathways involving a variety of channels, specifically, voltage-gated ion channels. One aspect of neuropathic pain is hyperexcitability in dorsal root ganglia (DRG) peripheral sensory neurons. Our study employs bifurcation theory to investigate the role of voltage-gated ion channels in inducing hyperexcitability as a consequence of spontaneous firing due to the common chemotherapy agent paclitaxel. Our mathematical investigation of a reductionist DRG neuron model comprised of sodium channel Na1.7, sodium channel Na1.8, delayed rectifier potassium channel, A-type transient potassium channel, and a leak channel suggests that Na1.8 and delayed rectifier potassium channel conductances are critical for hyperexcitability of small DRG neurons. Introducing paclitaxel into the model, our bifurcation analysis predicts that hyperexcitability is highest for a medium dose of paclitaxel, which is supported by multi-electrode array (MEA) recordings. Furthermore, our findings using MEA reveal that Na1.8 blocker A-803467 and delayed rectifier potassium enhancer L-alpha-phosphatidyl-D-myo-inositol 4,5-diphosphate, dioctanoyl (PIP) can reduce paclitaxel-induced hyperexcitability of DRG neurons. Our approach can be readily extended and used to investigate various other contributors of hyperexcitability in CIPN.
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