Elsevier

NeuroImage

Volume 47, Issue 3, September 2009, Pages 987-994
NeuroImage

Review
The influence of negative emotions on pain: Behavioral effects and neural mechanisms

https://doi.org/10.1016/j.neuroimage.2009.05.059Get rights and content

Abstract

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.

Introduction

The power emotions have over pain has been experienced by most of us in many facets. The headache that stops the minute the long-awaited visitor rings the door bell or the toothache that becomes unbearable after an argument with a colleague are well-known examples of this influence. For patients suffering from persistent pain this tight relationship between pain and emotions can have detrimental consequences. In their treatment of chronic pain, individuals with comorbid mental disorders feel more disabled and respond less favorably to rehabilitation than those with no co-occurring mental disorders (Dersh et al., 2002). Several population-based longitudinal studies have emerged supporting the hypothesis that mood disorders can increase the risk of developing chronic pain. Depressed, pain-free individuals for instance are on average two times more likely to develop chronic musculoskeletal pain than non-depressed, pain-free individuals (Magni et al., 1994, Carroll et al., 2004, Larson et al., 2004). Likewise, there is some evidence to suggest that anxiety disorders precede the onset of pain (Roy-Byrne et al., 2008). However, it should be noted that chronic pain in turn can lead to long lasting emotional disturbances often referred to as ‘secondary pain affect’ (Price, 2000). This might include worrying about the interference of pain with their life, difficulties of enduring pain over time and implications for the future. Often, this sets up a vicious circle where secondary pain affect aggravates pain which then fuels worrying and secondary pain affect. In a patient presenting with both, chronic pain and persistent mood changes, it is therefore often difficult – and maybe even clinically irrelevant – to determine the causal relationship between the two problems.

Current concepts of pain emphasize that the perception of pain is not necessarily linearly related to the noxious input, but is critically influenced by psychological variables. As a consequence of this assumed multidimensionality of pain, sensory aspects of pain (i.e., location, intensity and quality of pain) are differentiated and separately assessed from cognitive–affective aspects. That both dimensions can vary independently has been shown on a behavioral as well as on a neural level using hypnosis. Whereas hypnotic suggestions changing the sensory, but not the affective dimension lead to signal changes in the primary somatosensory cortex (Hofbauer et al., 2001), affective without sensory changes were correlated with activation in the anterior cingulate cortex (Rainville et al., 1997). In the light of such findings, it is not surprising that emotional factors commonly affect unpleasantness without necessarily changing the intensity of pain (Villemure and Bushnell, 2002, Villemure and Bushnell, 2009, Villemure et al., 2003).

The differentiation of the two dimensions has turned out to be particularly useful in explaining pain-related disability. For instance, in a series of experiments on patients with chronic low back pain, Crombez et al. (1999) showed that pain-related fear is a better predictor of pain-related disability than pain intensity. Furthermore, the differentiation is important in understanding the pain-alleviating effect of interventions primarily targeting cognitive–affective pain aspects. Benzodiazepines, for instance, have been shown to provide pain relief, although they – at least in a strict sense – have no analgesic properties. It can be assumed that the pain-reducing effect of these substances is at least partly mediated by reducing anxiety and thereby the unpleasantness of pain (Dellemijn and Fields, 1994). A similar mechanism might underlie the beneficial effect of relaxation techniques which are commonly used in chronic pain (Molton et al., 2007).

In this review, we will summarize current evidence for a modulation of pain by negative emotions and discuss potential neural mechanisms underlying this influence. Before proceeding, it should be noted that in the literature on pain modulation, emotional factors are often differentiated from cognitive factors. The first comprise short-lasting moods (e.g., contextual anxiety, anger) as well as longer lasting emotional states such as clinical forms of anxiety or depression. In contrast, mental processes such as attention, expectation or catastrophizing are commonly referred to as cognitive modulators of pain. However, given their strong interdependance the two components are almost impossible to separate. In clinical depression, for instance, negative mood as the most prominent feature is almost inevitably accompanied by automatic thoughts, cognitive distortions, dysfunctional beliefs, and information processing biases (Beck, 2008). Likewise, cognitive processes certainly also have a strong emotional component. For example, if a substance is believed to increase pain (nocebo expectation) it seems reasonable to assume that this not only changes expectations, but also leads to anticipatory anxiety. It therefore has to be emphasized that a cognitive modulation of pain inevitably comprises an emotional response and that the influence emotions have on pain most likely include cognitive operations. However, in this review we will focus on studies explicitly addressing emotional aspects, discuss their outcome particularly in reference to the mature literature on normal and pathological emotion processing and only refer to cognitive processing where the direct interaction aids in understanding underlying mechanisms. For a recent review on cognitive modulation of pain see Wiech et al. (2008b).

Section snippets

Studies on the effect of mood induction on experimental pain

According to the motivational priming theory (Lang, 1995), the experience of emotions is determined by two opponent motive systems: the appetitive system that is activated by appetitive stimuli (e.g., sex, food) and results in positive emotions and the defensive system activated by harmful or potentially harmful stimuli (e.g., threat, pain) and resulting in negatively valenced emotion. If one of these motive system is activated (primed), future responses emanating from that system will be

Studies on pain in patients with clinical mood disorders

Experimental mood inductions offer the advantage of a defined onset of negative mood relative to pain, ensuring that changes in pain follow changes in mood. However, it can be argued that they have a very short-lasting effect and can therefore only be a first approximation to the investigation of long-term changes occurring in persistent mood changes. Studies investigating changes in pain sensitivity in populations with clinical mood disorders are therefore valuable additional sources of

Mechanisms underlying the modulation of pain by emotion

How can a feeling of sadness or anxiety lead to changes in the perception of pain? Most brain regions showing altered pain processing in the experimental and clinical studies mentioned above are part of the descending pain modulatory system. It comprises prefrontal, anterior cingulate and insular cortices, amygdala, hypothalamus and brainstem structures like the periaqueductal grey (PAG), rostral ventromedial medulla, dorsolateral pons/tegmentum, and the descending projections to the spinal

Emotional modulation of pain: the influence of prefrontal regions

Although structures such as PAG, amygdala and insula are certainly key players in implementing emotional modulation of pain, they themselves seem to be governed by prefrontal cortex regions (Mohr et al., 2008). Direct evidence for a crucial role of the prefrontal cortex in pain modulation comes from neuroimaging studies on emotional regulation and its effect on pain perception. If subjects are taught to emotionally distance themselves from the negative affective impact of pain, the resulting

Future research directions

Despite the growing number of neuroimaging studies on emotional pain modulation there are still several open questions. First, studies using functional MRI to show changes in brain activity related to a change in perceived pain intensity are by nature correlative, not causal. Hence, data from these studies cannot prove a causal relationship, for instance between increased prefrontal cortex activity and the effect emotions have on pain. Techniques such as transcranial magnetic stimulation (TMS;

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