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Many clinical trials fail because of placebo responses. Prior therapeutic experiences and patients' expectations may affect the capacity to respond to placebos in chronic disorders.
Abrocitinib, an oral, once-daily Janus kinase 1 selective inhibitor, was effective and well tolerated in a phase 3 monotherapy trial of patients with moderate-to-severe atopic dermatitis (AD).
Irritable bowel syndrome (IBS) is a disorder involving dysfunctional brain-gut interactions characterized by chronic recurrent abdominal pain, altered bowel habits, and negative emotion. Previous studies have linked the habenula to the pathophysiology of negative emotion and pain. However, no studies to date have investigated habenular function in IBS patients. In this study, we investigated the resting-state functional connectivity (rsFC) and effective connectivity of the habenula in 34 subjects with IBS and 34 healthy controls and assessed the feasibility of differentiating IBS patients from healthy controls using a machine learning method. Our results showed significantly enhanced rsFC of the habenula-left dorsolateral prefrontal cortex (dlPFC) and habenula-periaqueductal grey (PAG, dorsomedial part), as well as decreased rsFC of the habenula-right thalamus (dorsolateral part), in the IBS patients compared with the healthy controls. Habenula-thalamus rsFC was positively correlated with pain intensity (r = .467, p = .005). Dynamic causal modeling (DCM) revealed significantly decreased effective connectivity from the right habenula to the right thalamus in the IBS patients compared to the healthy controls that was negatively correlated with disease duration (r = -.407, p = .017). In addition, IBS was classified with an accuracy of 71.5% based on the rsFC of the habenula-dlPFC, habenula-thalamus, and habenula-PAG in a support vector machine (SVM), which was further validated in an independent cohort of subjects (N = 44, accuracy = 65.2%, p = .026). Taken together, these findings establish altered habenular rsFC and effective connectivity in IBS, which extends our mechanistic understanding of the habenula's role in IBS.
Itch and pain are important attention-demanding sensations that allow adaptive responses to potential bodily harm. An attentional bias towards itch and pain stimuli, i.e. preferential attention allocation towards itch- and pain-related information, has been found in healthy, as well as patient groups. However, it remains unclear whether attentional bias for itch and pain differs from a general bias towards negative information. Therefore, this study investigated attentional bias towards itch and pain in 70 itch- and pain-free individuals. In an attention task, itch- and pain-related stimuli, as well as negative stimuli, were presented alongside neutral stimuli. The results did not indicate an attentional bias towards itch-, pain-, and negative visual information. This finding suggests that people without itch and pain symptoms do not prioritize itch- and pain-related information above neutral information. Future research should investigate whether attention towards itch- and pain-related information might be biased in patients with chronic itch and pain.
The present study examined pre- to post-treatment changes in volumes for brain structures known to be associated with pain processing (thalamus, caudate, putamen, pallidum, hippocampus, amygdala, and accumbens) following an interdisciplinary pain management program.
Background and aims Recognition of the biopsychosocial aspects of pain is important for a true understanding of the burden of pain and the necessity of pain management. Biopsychosocial aspects of pain may differ between countries and cultures. Market research methods can be well suited and effective for assessing patient perspectives of pain and biopsychosocial differences. We conducted and combined 3 cross-sectional, international surveys to document the impact of pain on physical and emotional aspects of life, as well as quality of life (QOL). Methods Online panelists from 24 countries took part in our surveys in 2014, 2016, and 2017. Fourteen countries (Australia, Brazil, Canada, China, Germany, Italy, Japan, Poland, Russia, United Kingdom, United States, Mexico, Sweden, Saudi Arabia) contributed data in all 3 surveys and comprise the analysis population. A Global Pain Index (GPI) was constructed using 8 questions in 3 categories: Physical (frequency, duration, intensity of pain), Emotional (anxiety, impact on self-esteem, happiness), and Impact on QOL and ability to enjoy life. Each item was scored as the percentage of respondents meeting a prespecified threshold indicative of a substantial pain impact. Scores for the items within each category were averaged to obtain a category score, category scores were averaged to obtain a total score for each survey, and total scores from each survey were averaged to obtain a final combined score. Scores were assessed for the overall population, by individual countries, by age and gender, and by self-identified pain-treatment status (treat immediately, wait, never treat). Results Of the 50,952 adult respondents, 28,861 (56.6%) had ever experienced musculoskeletal pain; 50% of those with pain had pain with a multifaceted impact based on the GPI (Physical: 51%; Emotional: 40%; QOL Impact: 59%). Russia (57%) and Poland (56%) had the highest scores; Mexico (46%), Germany (47%), and Japan (47%) had the lowest. GPI score was higher in women (52%) than men (48%), and initially increased with age through age 54 (18‒24 years: 45%; 25‒34 years: 52%; 35‒44 years: 53%; 45‒54 years: 54%), after which it decreased again (55‒64 years: 51%; ≥65 years: 45%). A majority (65%) of respondents wait to treat their pain, whereas 21% treat their pain immediately and 14% never treat pain. The most common reason for waiting (asked in survey 3 only) was to avoid taking medication. Conclusions In this combined analysis of 3 international surveys using a novel biopsychosocial pain assessment tool, pain had a substantial impact on ~50% of respondents' lives, spanning physical (51%), emotional (40%), and QOL effects (59%). Despite the substantial impact, a majority of patients tried to avoid treating their pain. Implications Clinicians should take a biopsychosocial approach to pain by asking patients not only about the presence and severity of pain, but the extent to which it affects various aspects of their lives and daily functioning. Patients may also need education about the efficacy and safety of available treatments for self-management of pain. The GPI may be a useful new tool for future studies of the biopsychosocial effects of pain in large populations.
The descending serotonergic pathway, from the brainstem to spinal cord, modulates various aspects of pain processing. The spinal 5-hydroxytryptamine (5-HT) and 5-HT receptors play pivotal roles in pain modulation. Perospirone is a novel atypical antipsychotic that serves as a 5-hydroxytryptamine (5-HT) receptor agonist, a 5-HT receptor antagonist, and a dopamine D receptor antagonist. Little is known about the effect of perospirone on pain transmission. Here, we explored whether perospirone attenuated neuropathic and inflammatory pain in the spinal cord. A chronic constriction injury to the sciatic nerve was induced in male Sprague-Dawley rats. We evaluated the effects of intrathecal administration of perospirone (10, 20, or 40 μg) on mechanical and cold hyperalgesia using the electronic von Frey and cold plate tests, respectively. Normal rats were assessed in terms of inflammatory nociception using the formalin test and for motor coordination employing the rotarod test. To define the mechanism underlying the action of perospirone, the effects of intrathecal pretreatment with the 5-HT receptor antagonist WAY-100635, the 5-HT receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-aminopropane (DOI), and the dopamine D receptor agonist sumanirole on perospirone action were examined using the electronic von Frey test and cold plate test. Perospirone dose-dependently alleviated mechanical and cold hyperalgesia, but not inflammatory nociception in the spinal cord, and affected motor coordination. WAY-100635 reversed the antihyperalgesic action of perospirone significantly, but neither DOI nor sumanirole exhibited such an effect. We conclude that perospirone attenuates mechanical and cold hyperalgesia principally via 5-HT receptor activation in the spinal cord, and the agent is a promising novel candidate for neuropathic pain relief.
To investigate the relationship of emotion regulation strategies (i.e., emotional suppression and reappraisal) with pain catastrophizing, fear of pain, pain intensity, worry, and depression as function of age in samples of older and younger adults.
Chronic pruritus is a cardinal symptom of the inflammatory skin disease atopic dermatitis (AD). Pathogenic mechanisms in the periphery, spinal cord and the brain have been implicated in AD-related pruritus. Therefore, both systemic and topical administration of drugs could potentially provide relief. Despite efforts to elucidate the mechanisms behind AD-related pruritus and the relative contribution of peripheral nervous system and central nervous system (CNS), specific and successful treatment options have not yet been developed. Several small molecule drugs are currently being investigated to treat AD and AD-related pruritus. These small molecule drugs can be applied systemically but also topically, as they are able to penetrate into the skin due to their small size. Small molecule drugs specifically targeting peripheral itch transmission, e.g. peripherally selective κ-opioid receptors agonists and neurokinin 1 receptors antagonists, have so far been unable to improve AD-related pruritus when applied systemically, possibly because of the lack of CNS activity. Current evidence from clinical and preclinical trials with centrally acting or peripherally selective oral κ-opioid receptors agonists implies that CNS activity is required for an antipruritic effect. CNS activity is, however, directly associated with CNS-mediated side-effects. On the other hand, topical application of small molecules with anti-inflammatory activity such as Janus kinase inhibitors and phosphodiesterase 4 inhibitors, and also of κ-opioid receptor agonists, has shown promising results regarding their ability to reduce AD-related pruritus. In conclusion, topical application of anti-inflammatory compounds appears to be a highly promising strategy for the treatment of AD-related pruritus.