Dyspnea and pain share emotion-related brain network

Abstract

The early detection of stimuli signalling threat to an organism is a crucial evolutionary advantage. For example, the perception of aversive bodily sensations such as dyspnea and pain strongly motivates fast adaptive behaviour to ensure survival. Their similarly threatening and motivating characters led to the speculation that both sensations are mediated by common brain areas, which has also been suggested by neuroimaging studies on either dyspnea or pain. By using functional magnetic resonance imaging (fMRI), we formally tested this hypothesis and compared the cortical processing of perceived heat pain and resistive load induced dyspnea in the same group of participants. Here we show that the perception of both aversive sensations is processed in similar brain areas including the insula, dorsal anterior cingulate cortex, amygdala and medial thalamus. These areas have a documented role in the processing of emotions such as fear and anxiety. Thus, the current study highlights the role of a common emotion-related human brain network which underlies the perception of aversive bodily sensations such as dyspnea and pain. This network seems crucial for translating the threatening character of different bodily signals into behavioural consequences that promote survival.

Introduction

Charles Darwin (1872) already proposed that the early detection of threatening and potentially harmful stimuli is a crucial evolutionary advantage because it allows the fast initiation of adequate actions that promote survival of the organism, i.e. fight or flight behaviour. Bodily sensations such as dyspnea (breathlessness) and pain are key examples for those threatening and potentially harmful stimuli that, although they have distinct features, share several similarities. Both are subjectively perceived sensations, signal direct bodily disturbances and strongly motivate rapid adaptive behaviour to regain homeostatic balance (Banzett et al., 2000b, Tracey and Mantyh, 2007). Most obvious is their common aversive and threatening character signalling potential risk for survival, including suffocation and severe tissue damage.

Besides this important alarm function, recurrent or chronic experiences of dyspnea or pain are prominent and frightening symptoms in various cardiopulmonary diseases such as asthma and chronic obstructive pulmonary disease (COPD) or in various pain syndromes (American Thoracic Society, 1999, International Association for the Study of Pain, 1994), which are associated with great individual burden as well as socio-economic costs. Recent research has shown that many patients with dyspnea as well as pain suffer from comorbid emotional symptoms such as anxiety and depression (Hamelsky and Lipton, 2006, Maurer et al., 2008), which can also have a considerable impact on the perception of both sensations and disease management (e.g., self medication, physician visits, activity levels) (Leeuw et al., 2007, von Leupoldt and Dahme, 2007). However, whereas many previous studies led to a solid body of knowledge on perceptual and neural mechanisms of pain (Tracey and Mantyh, 2007), only little is known about the mechanisms of dyspnea. In particular, the neural processing of dyspnea and possible interactions with emotional states and motivated behaviour are poorly understood (von Leupoldt and Dahme, 2005), which contributes to the current lack of efficient treatment options for chronic dyspnea.

The first neuroimaging studies on dyspnea (Banzett et al., 2000a, Corfield et al., 1995, Evans et al., 2002, Liotti et al., 2001, Macey et al., 2006, McKay et al., 2008, Peiffer et al., 2001, Peiffer et al., 2008, von Leupoldt et al., 2008) and the various neuroimaging studies on pain (Price, 2000, Tracey and Mantyh, 2007) have suggested similarities in the cortical processing of both sensations, which include prominent activations of emotion-related areas such as the insula and anterior cingulate cortex. Therefore, it has been speculated for some time that the perception of aversive bodily sensations such as dyspnea and pain is at least in part processed by a common brain network (Banzett et al., 2000b, Craig, 2002, Critchley, 2005, Peiffer, 2008, Schön et al., 2008, von Leupoldt and Dahme, 2005).

To address this question, we collected functional magnetic resonance imaging (fMRI) data while healthy participants repeatedly underwent conditions of mild dyspnea, severe dyspnea, mild pain and severe pain, which were induced by breathing through inspiratory flow resistive loads and by contact heat pain, respectively. We hypothesized that, besides distinct brain activation patterns for dyspnea and pain, both sensations would be processed in similar brain areas such as the insula and anterior cingulate cortex.