The perception of pain is subject to powerful influences. Understanding how these are mediated at a neuroanatomical and neurobiological level provides us with valuable information that has a direct ...impact on our ability to harness positive and minimize negative effects therapeutically, as well as optimize clinical trial designs when developing new analgesics. This is particularly relevant for placebo and nocebo effects. New research findings have directly contributed to an increased understanding of how placebo and nocebo effects are produced and what biological and psychological factors influence variances in the magnitude of the effect. The findings have relevance for chronic pain states and other disorders, where abnormal functioning of crucial brain regions might affect analgesic outcome even in the normal therapeutic setting.
The idea that pain can lead to feelings of frustration, worry, anxiety and depression seems obvious, particularly if it is of a chronic nature. However, there is also evidence for the reverse causal ...relationship in which negative mood and emotion can lead to pain or exacerbate it. Here, we review findings from studies on the modulation of pain by experimentally induced mood changes and clinical mood disorders. We discuss possible neural mechanisms underlying this modulatory influence focusing on the periaqueductal grey (PAG), amygdala, anterior cingulate cortex (ACC) and anterior insula as key players in both, pain and affective processing.
Pain is a subjective sensory experience that can, mostly, be reported but cannot be directly measured or quantified. Nevertheless, a suite of biomarkers related to mechanisms, neural activity, and ...susceptibility offer the possibility—especially when used in combination—to produce objective pain-related indicators with the specificity and sensitivity required for diagnosis and for evaluation of risk of developing pain and of analgesic efficacy. Such composite biomarkers will also provide improved understanding of pain pathophysiology.
This Perspective highlights the significance of chronic pain, its underpinning biology, and the need for composite biomarker signatures alongside self-report. Combining evidence from animal and human research spanning genetics through to neuroimaging, Tracey et al. highlight a few key areas of promise.
Clinical pain is a serious public health issue. Treatment of pain-related suffering requires knowledge of how pain signals are initially interpreted and subsequently transmitted and perpetuated. This ...review article is one of three reviews in this issue of Neuron that address our understanding of the pain process and possible solutions to the problem from both cellular- and systems-level viewpoints.
Our understanding of the neural correlates of pain perception in humans has increased significantly since the advent of neuroimaging. Relating neural activity changes to the varied pain experiences has led to an increased awareness of how factors (e.g., cognition, emotion, context, injury) can separately influence pain perception. Tying this body of knowledge in humans to work in animal models of pain provides an opportunity to determine common features that reliably contribute to pain perception and its modulation. One key system that underpins the ability to change pain intensity is the brainstem's descending modulatory network with its pro- and antinociceptive components. We discuss not only the latest data describing the cerebral signature of pain and its modulation in humans, but also suggest that the brainstem plays a pivotal role in gating the degree of nociceptive transmission so that the resultant pain experienced is appropriate for the particular situation of the individual.
The coronavirus disease 2019 (COVID-19) pandemic is having a profound effect on all aspects of society, including mental health and physical health. We explore the psychological, social, and ...neuroscientific effects of COVID-19 and set out the immediate priorities and longer-term strategies for mental health science research. These priorities were informed by surveys of the public and an expert panel convened by the UK Academy of Medical Sciences and the mental health research charity, MQ: Transforming Mental Health, in the first weeks of the pandemic in the UK in March, 2020. We urge UK research funding agencies to work with researchers, people with lived experience, and others to establish a high level coordination group to ensure that these research priorities are addressed, and to allow new ones to be identified over time. The need to maintain high-quality research standards is imperative. International collaboration and a global perspective will be beneficial. An immediate priority is collecting high-quality data on the mental health effects of the COVID-19 pandemic across the whole population and vulnerable groups, and on brain function, cognition, and mental health of patients with COVID-19. There is an urgent need for research to address how mental health consequences for vulnerable groups can be mitigated under pandemic conditions, and on the impact of repeated media consumption and health messaging around COVID-19. Discovery, evaluation, and refinement of mechanistically driven interventions to address the psychological, social, and neuroscientific aspects of the pandemic are required. Rising to this challenge will require integration across disciplines and sectors, and should be done together with people with lived experience. New funding will be required to meet these priorities, and it can be efficiently leveraged by the UK's world-leading infrastructure. This Position Paper provides a strategy that may be both adapted for, and integrated with, research efforts in other countries.
Pain is a highly complex and subjective experience that is not linearly related to the nociceptive input. What is clear from anecdotal reports over the centuries and more recently from animal and ...human experimentation is that nociceptive information processing and consequent pain perception is subject to significant pro- and anti-nociceptive modulations. These modulations can be initiated reflexively or by contextual manipulations of the pain experience including cognitive and emotional factors. This provides a necessary survival function since it allows the pain experience to be altered according to the situation rather than having pain always dominate. The so-called descending pain modulatory network involving predominantly medial and frontal cortical areas, in combination with specific subcortical and brain stem nuclei appears to be one key system for the endogenous modulation of pain. Furthermore, recent findings from functional and anatomical neuroimaging support the notion that an altered interaction of pro- and anti-nociceptive mechanisms may contribute to the development or maintenance of chronic pain states. Research on the involved circuitry and implemented mechanisms is a major focus of contemporary neuroscientific research in the field of pain and should provide new insights to prevent and treat chronic pain states.
Imaging of the living human brain is a powerful tool to probe the interactions between brain, gut and microbiome in health and in disorders of brain-gut interactions, in particular IBS. While altered ...signals from the viscera contribute to clinical symptoms, the brain integrates these interoceptive signals with emotional, cognitive and memory related inputs in a non-linear fashion to produce symptoms. Tremendous progress has occurred in the development of new imaging techniques that look at structural, functional and metabolic properties of brain regions and networks. Standardisation in image acquisition and advances in computational approaches has made it possible to study large data sets of imaging studies, identify network properties and integrate them with non-imaging data. These approaches are beginning to generate brain signatures in IBS that share some features with those obtained in other often overlapping chronic pain disorders such as urological pelvic pain syndromes and vulvodynia, suggesting shared mechanisms. Despite this progress, the identification of preclinical vulnerability factors and outcome predictors has been slow. To overcome current obstacles, the creation of consortia and the generation of standardised multisite repositories for brain imaging and metadata from multisite studies are required.
Relief fits the definition of a reward. Unlike other reward types the pleasantness of relief depends on the violation of a negative expectation, yet this has not been investigated using neuroimaging ...approaches. We hypothesized that the degree of negative expectation depends on state (dread) and trait (pessimism) sensitivity. Of the brain regions that are involved in mediating pleasure, the nucleus accumbens also signals unexpected reward and positive prediction error. We hypothesized that accumbens activity reflects the level of negative expectation and subsequent pleasant relief. Using fMRI and two purpose-made tasks, we compared hedonic and BOLD responses to relief with responses during an appetitive reward task in 18 healthy volunteers. We expected some similarities in task responses, reflecting common neural substrates implicated across reward types. However, we also hypothesized that relief responses would differ from appetitive rewards in the nucleus accumbens, since only relief pleasantness depends on negative expectations. The results confirmed these hypotheses. Relief and appetitive reward task activity converged in the ventromedial prefrontal cortex, which also correlated with appetitive reward pleasantness ratings. In contrast, dread and pessimism scores correlated with relief but not with appetitive reward hedonics. Moreover, only relief pleasantness covaried with accumbens activation. Importantly, the accumbens signal appeared to specifically reflect individual differences in anticipation of the adverse event (dread, pessimism) but was uncorrelated to appetitive reward hedonics. In conclusion, relief differs from appetitive rewards due to its reliance on negative expectations, the violation of which is reflected in relief-related accumbens activation.
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