Investigating the specificity of the neurologic pain signature against breathlessness and finger opposition

Brain biomarkers of pain, including pain-predictive “signatures” based on brain activity, can provide measures of neurophysiological processes and potential targets for interventions. A central issue relates to the specificity of such measures, and understanding their current limits will both advance their development and explore potentially generalizable properties of pain to other states. Here, we used 2 data sets to test the neurologic pain signature (NPS), an established pain neuromarker. In study 1, brain activity was measured using high-field functional magnetic resonance imaging (7T fMRI, N = 40) during 5 to 25 seconds of experimental breathlessness (induced by inspiratory resistive loading), conditioned breathlessness anticipation, and finger opposition. In study 2, we assessed anticipation and breathlessness perception (3T, N = 19) under blinded saline (placebo) and remifentanil administration. The NPS responded to breathlessness, anticipation, and finger opposition, although no direct comparisons with painful events were possible. Local NPS patterns in anterior or midinsula, S2, and dorsal anterior cingulate responded to breathlessness and finger opposition and were reduced by remifentanil. Local NPS responses in the dorsal posterior insula did not respond to any manipulations. Therefore, significant global NPS activity alone is not specific for pain, and we offer insight into the overlap between NPS responses, breathlessness, and somatomotor demand

Dyspnea-related cues engage the prefrontal cortex - evidence from functional brain imaging in COPD

Dyspnea is the major source of disability in chronic obstructive pulmonary disease (COPD). In COPD, environmental cues (e.g. the prospect of having to climb stairs) become associated with dyspnea, and may trigger dyspnea even before physical activity commences. We hypothesised that brain activation relating to such cues would be different between COPD patients and healthy controls, reflecting greater engagement of emotional mechanisms in patients. Methods: Using FMRI, we investigated brain responses to dyspnea-related word cues in 41 COPD patients and 40 healthy age-matched controls. We combined these findings with scores of self-report questionnaires thus linking the FMRI task with clinically relevant measures. This approach was adapted from studies in pain that enables identification of brain networks responsible for pain processing despite absence of a physical challenge. Results: COPD patients demonstrate activation in the medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC) which correlated with the visual analogue scale (VAS) response to word cues. This activity independently correlated with patient-reported questionnaires of depression, fatigue and dyspnea vigilance. Activation in the anterior insula, lateral prefrontal cortex (lPFC) and precuneus correlated with the VAS dyspnea scale but not the questionnaires. Conclusions: Our findings suggest that engagement of the brain's emotional circuitry is important for interpretation of dyspnea-related cues in COPD, and is influenced by depression, fatigue, and vigilance. A heightened response to salient cues is associated with increased symptom perception in chronic pain and asthma, and our findings suggest such mechanisms may be relevant in COPD

Scale interactions between the MJO and the western maritime continent

State-of-the-art regional climate model simulations that are able to resolve key mesoscale circulations are used, for the first time, to understand the interaction between the large-scale convective environment of the MJO and processes governing the strong diurnal cycle over the islands of the Maritime Continent (MC). Convection is sustained in the late afternoon just inland of the coasts due to sea breeze convergence. Previous work has shown that the variability in MC rainfall associated with the MJO is manifested in changes to this diurnal cycle; land-based rainfall peaks before the active convective envelope of the MJO reaches the MC, whereas oceanic rainfall rates peak whilst the active envelope resides over the region. The model simulations show that the main controls on oceanic MC rainfall in the early active MJO phases are the large-scale environment and atmospheric stability, followed by high oceanic latent heat flux forced by high near-surface winds in the later active MJO phases. Over land, rainfall peaks before the main convective envelope arrives (in agreement with observations), even though the large-scale convective environment is only moderately favourable for convection. The causes of this early rainfall peak are convective triggers from land-sea breeze circulations that are strong due to high surface insolation and surface heating. During the peak MJO phases cloud cover increases and surface insolation decreases, which weakens the strength of the mesoscale circulations and reduces land-based rainfall, even though the large-scale environment remains favourable for convection at this time. Hence, scale interactions are an essential part of the MJO transition across the MC

Breathlessness and inflammation: relationship and implications

Purpose of Review: Breathlessness and chronic inflammation both span a wide range of disease contexts and hold prognostic significance. The possibility of a causal relationship between the two has been hypothesised. The aims of this article are 1) to review the intersections between breathlessness and inflammation in the literature, 2) to describe potential mechanisms connecting the two phenomena, and 3) to discuss the potential clinical implications of a causal relationship. Recent findings: There is a very limited literature exploring the relationship between systemic inflammation and breathlessness in COPD, heart failure and cancer. One large study in cancer patients is suggestive of a weak association between self-reported breathlessness and inflammation. Studies exploring the relationship between inflammation and MRC Dyspnoea grade have produced inconsistent findings. Though a causal relationship has not yet been demonstrated, this relationship might be mediated through the effects of both inflammation and breathlessness on the skeletal muscle and stress hormone systems. Summary: There is much progress to be made in this area. Interventional studies, evaluating the impact of anti-inflammatory interventions on breathlessness, are needed to help determine whether a causal relationship exists. If proven, this relationship might have important implications for both the treatment and impact of breathlessness

The evidence base for oxygen for chronic refractory breathlessness: issues, gaps, and a future work plan

Breathlessness or “shortness of breath”, medically termed dyspnoea, remains a devastating problem for many people and those who care for them. As a treatment intervention, administration of opioids to relieve breathlessness is an area where progress has been made with the development of an evidence base. As evidence in support of opioids has accumulated, so has our collective understanding about trial methodology, research collaboration and infrastructure that is crucial to generate reliable research results for palliative care clinical settings. Analysis of achievements to date and what it takes to accomplish these studies provides important insights into knowledge gaps needing further research as well as practical insight into design of pharmacological and non-pharmacological intervention trials in breathlessness and palliative care. This paper presents current understanding of opioids for treating breathlessness, what is still unknown as priorities for future research and highlights methodological issues for consideration in planned studies.This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors

DYSPNEA FROM NEUROPSYCHYATRIC PERSPECTIVE: A NARRATIVE REVIEW

Dyspnea or breathlessness is a term primarily used in respiratory medicine. Nevertheless, in the last fifteen years, studies from other fields focus on the affective component of this complex phenomenon due to the frequent observation that psychological states can cause or be caused by dyspnea. Research so far shows that besides the biological component, dyspnea has a strong emotional and psychosocial determinant. This means that apart from its biological factors, dyspnea and its intensity are affected by emotions, personality, anxiety and depression, etc. Individuals with psychiatric disorders, in the same conditions, will evaluate their dyspnea as more intense and disturbing compared to individuals without psychiatric comorbidity. Emotional states in healthy individuals can amplify the sense of dyspnea which is of extreme importance for clinical practice in order to consider the whole person and not just the symptom which is being presented. Also, dyspnea seems to be frequent complaint in some groups of patients with psychiatric disorders (e.g.panic disorder), where the fear of suffocation is presented as clinical symptom. Further research of dyspnea as a complex, multicomponent phenomenon, can contribute to better treatment options and better differential diagnosis concerning possible psychiatric background of physical symptoms

Breathlessness and inflammation: potential relationships and implications.

PURPOSE OF REVIEW: Breathlessness and chronic inflammation both span a wide range of disease contexts and hold prognostic significance. The possibility of a causal relationship between the two has been hypothesized. The aims of this article are to review the intersections between breathlessness and inflammation in the literature, describe potential mechanisms connecting the two phenomena, and discuss the potential clinical implications of a causal relationship. RECENT FINDINGS: There is a very limited literature exploring the relationship between systemic inflammation and breathlessness in chronic obstructive pulmonary disease, heart failure, and cancer. One large study in cancer patients is suggestive of a weak association between self-reported breathlessness and inflammation. Studies exploring the relationship between inflammation and Medical Research Council Dyspnoea grade in chronic obstructive pulmonary disease patients have produced inconsistent findings. Although a causal relationship has not yet been proven, there is evidence to support the existence of potential mechanisms mediating a relationship. This evidence points to a role for the skeletal muscle and stress hormone systems. SUMMARY: There is much progress to be made in this area. Interventional studies, evaluating the impact of anti-inflammatory interventions on breathlessness, are needed to help determine whether a causal relationship exists. If proven, this relationship might have important implications for both the treatment and impact of breathlessness.R.R. was funded by a National Institute for Health Research (NIHR) Doctoral Research Fellowship Award from January 2013–December 2015