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The placebo effect can be defined as the improvement of symptoms in a patient after the administration of an innocuous substance in a context that induces expectations regarding its effects. During recent years, it has been discovered that the placebo response not only has neurobiological functions on analgesia, but that it is also capable of generating effects on the immune and endocrine systems. The possible integration of changes in different systems of the organism could favor the well-being of the individuals and go hand in hand with conventional treatment for multiple diseases. In this sense, classic conditioning and setting expectations stand out as psychological mechanisms implicated in the placebo effect. Recent advances in neuroimaging studies suggest a relationship between the placebo response and the opioid, cannabinoid, and monoaminergic systems. Likewise, a possible immune response conditioned by the placebo effect has been reported. There is evidence of immune suppression conditioned through the insular cortex and the amygdala, with noradrenalin as the responsible neurotransmitter. Finally, a conditioned response in the secretion of different hormones has been determined in different studies; however, the molecular mechanisms involved are not entirely known. Beyond studies about its mechanism of action, the placebo effect has proved to be useful in the clinical setting with promising results in the management of neurological, psychiatric, and immunologic disorders. However, more research is needed to better characterize its potential use. This review integrates current knowledge about the psycho-neuro-endocrine-immune basis of the placebo effect and its possible clinical applications.
Learn More >The central pathophysiological mechanisms underlying irritable bowel syndrome (IBS), a female-predominant gastrointestinal disorder characterized by abdominal pain and abnormal bowel habits, remain poorly understood. IBS patients often report that chronic stress exacerbates their symptoms. Brain imaging studies have revealed that the amygdala, a stress-responsive brain region, of IBS patients is overactive when compared to healthy controls. Previously, we demonstrated that downregulation of the glucocorticoid receptor (GR) in the central nucleus of the amygdala (CeA) underlies stress-induced visceral hypersensitivity in female rats. In the current study, we aimed to evaluate in the CeA of female rats whether chronic water avoidance stress (WAS) alters DNA methylation of the GR exon 1 promoter region, a region homologous to the human GR promoter. As histone deacetylase (HDAC) inhibitors are able to change DNA methylation, we also evaluated whether administration of the HDAC inhibitor trichostatin A (TSA) directly into the CeA prevented WAS-induced increases in DNA methylation of the GR exon 1 promoter. We found that WAS increased overall and specific CpG methylation of the GR promoter in the CeA of female rats, which persisted for up to 28 days. Administration of the TSA directly into the CeA prevented these stress-induced changes of DNA methylation at the GR promoter. Our results suggest that, in females, changes in DNA methylation are involved in the regulation of GR expression in the CeA. These changes in DNA methylation may contribute to the central mechanisms responsible for stress-induced visceral hypersensitivity.
Learn More >International guidelines recommend diaries in migraine trials for prospective collection of headache symptoms. Studies in other patient populations suggest higher adherence with electronic diaries instead of pen-and-paper. This study examines the feasibility of a text message-based (texting) diary for children and adolescents with headache.
Learn More >Noxious pain signals are transduced in the peripheral nervous system as action potentials, which rely on the activities of voltage-gated sodium channels (NaVs). Blocking NaVs is thus a valuable strategy for pain treatment. Here, we report the characterization of a novel NaVs antagonist, 2-(2-(diethylamino)ethyl)indeno[1,2,3-de]phthalazin-3(2H)-one (C65780), and investigation of its action mechanisms. C65780 inhibited the resting NaV1.7, NaV1.8, and NaV1.9 channels with IC50s of 11.3 ± 0.4 μM, 2.7 ± 0.3 μM and 19.2 ± 2.3 μM, respectively. Mechanistic analysis revealed that C65780 quickly bound to its high-affinity receptor site in NaV1.7 as formed by the fast inactivation process and stabilized the channels in a slowly recovering state, for which it facilitated NaV1.7 channels' inactivation by shifting their inactivation-voltage relationship in the hyperpolarizing direction, increasing the plateau proportion of inactivated channels, and blunting their time-dependent recovery. The slow inactivation of NaV1.7, however, is not involved in the action of C65780. In DRG neurons, C65780 also inhibited activity of NaVs, thus dampening neuronal excitability. These effects parlayed into a broad efficacy of orally administrated C65780 in various models of pain, with an efficacy comparable to the antidepressant/neuropathic pain drug Amitriptyline. Excitingly, C65780 demonstrated weaker inactivated state inhibition of related NaV1.4 and NaV1.5 channels compared to amitriptyline, and no toxicity or inhibition of locomotion in a forced-swimming test was observed in mice at pain-relieving doses. These results demonstrate that C65780 acts by trapping NaVs in the inactivated and slowly-recovering state to produce pain relief and may represent an excellent starting compound for developing analgesics.
Learn More >Despite concerns about long-term dependence, opioids remain the mainstay of treatment for acute pain from traumatic injuries. Additionally, early pain management has been associated with improved long-term outcomes in injured patients. We sought to identify the patterns of prehospital pain management across the United States.
Learn More >The bidirectional relationship between anxiety and chronic pain in youth is well-known, but how anxiety contributes to the maintenance of pediatric chronic pain needs to be elucidated. Sensitivity to pain traumatization (SPT), an individual's propensity to develop responses to pain that resemble a traumatic stress response, may contribute to the mutual maintenance of anxiety and pediatric chronic pain. A clinical sample of youth (aged 10-18 years) with chronic pain completed a measure of SPT at baseline and rated their anxiety and pain characteristics for seven consecutive days at baseline and at three-month follow-up. Multiple linear regression analyses were conducted to model whether SPT moderated the relationship between baseline anxiety and pain intensity, unpleasantness, and interference three months later. SPT significantly moderated the relationship between anxiety and pain intensity. High anxiety youth with high SPT reported increased pain intensity three months later, while high anxiety youth with low SPT did not. High anxiety youth who experience pain as potentially traumatizing are more likely to report higher pain intensity three months later than high-anxiety youth who do not. Future research should examine whether children's propensity to become traumatized by their pain predicts the development of chronic pain and response to intervention.
Learn More >Cogniphobia refers to the fear and avoidance of cognitive exertion, believed to cause or exacerbate headache. The objective of the present study was to demonstrate associations between cogniphobia and key fear-avoidance constructs.
Learn More >This study aimed to explore and compare the association between psychosocial factors, sleep, central sensitization, and chronic neck, back, limbs, and multiregional pain and disability.
Learn More >Australian people living with chronic pain (n=206; 90% female) and carers (n=10; 40% female) described their pain care priorities (eDelphi, Round 1). A coding framework was inductively derived from 842 pain care priorities (9 categories, 52 priorities) including: validation; communication; multidisciplinary approaches; holistic care; partnerships; practitioner knowledge; self-management; medicines and diagnosis.
Learn More >The Patient-Reported Outcomes Information System (PROMIS®) is more and more extensively being used in medical literature in patients with an orthopedic fracture. Yet, many articles studied heterogeneous groups with chronic orthopedic disorders in which fracture patients were included as well. At this moment, there is no systematic overview of the exact use of PROMIS measures in the orthopedic fracture population. Therefore this review aimed to provide an overview of the PROMIS health domains physical health, mental health and social health in patients suffering an orthopedic fracture.
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