ReviewThe influence of negative emotions on pain: Behavioral effects and neural mechanisms
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;
References (130)
- et al.
Can anxiety help us tolerate pain?
Pain
(1991) - et al.
Human brain mechanisms of pain perception and regulation in health and disease
Eur. J. Pain
(2005) - et al.
Great expectations: what can fMRI research tell us about psychological phenomena?
Int. J. Psychophysiol.
(2009) - et al.
Pain perception in major depression depends on pain modality
Pain
(2005) - et al.
Decreased sensitivity to experimental pain in adjustment disorder
Eur. J. Pain
(2006) - et al.
Influence of gender and hemispheric lateralization on heat pain perception in major depression
J. Psychiatr. Res.
(2003) - et al.
Increased prefrontal activation during pain perception in major depression
Biol. Psychiatry
(2007) - et al.
When words are painful: unraveling the mechanisms of the nocebo effect
Neuroscience
(2007) The physiological basis of transcranial magnetic stimulation
Trends Cogn. Sci.
(2008)- et al.
Mechanisms of placebo analgesia: rACC recruitment of a subcortical antinociceptive network
Pain
(2006)
Neurocognitive mechanisms of anxiety: an integrative account
Trends Cogn. Sci.
Confidence in beliefs about pain predicts expectancy effects on pain perception and anticipatory processing in right anterior insula
Pain
Depression as a risk factor for onset of an episode of troublesome neck and low back pain
Pain
The basolateral amygdala modulates specific sensory memory representations in the cerebral cortex
Neurobiol. Learn Mem.
The effect of experimentally induced anxiety on the experience of pressure pain
Pain
Pain-related fear is more disabling than pain itself: evidence on the role of pain-related fear in chronic back pain disability
Pain
Affective pictures processing, attention, and pain tolerance
Pain
Do benzodiazepines have a role in chronic pain management?
Pain
Anticipatory brainstem activity predicts neural processing of pain in humans
Pain
Conditioned stress-induced analgesia in humans
Eur. J. Pain
Clinical correlates of stress-induced analgesia: evidence from pharmacological studies
Pain
Contributions of the anterior cingulate cortex and amygdala to pain- and fear-conditioned place avoidance in rats
Pain
Descending modulation of pain
Neurosci. Biobehav. Rev.
Cerebral blood flow changes associated with experimental pain stimulation in patients with major depression
J. Affect Disord.
Altered cerebral response to noxious heat stimulation in patients with somatoform pain disorder
Pain
Determining anatomical connectivities between cortical and brainstem pain processing regions in humans: a diffusion tensor imaging study in healthy controls
Pain
Interoceptive sensitivity and emotion processing: an EEG study
Int. J. Psychophysiol.
Evidence of dysfunctional pain inhibition in Fibromyalgia reflected in rACC during provoked pain
Pain
Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition
Pain
Depression and changed pain perception: hints for a central disinhibition mechanism
Pain
Cholecystokinin-octapeptide antagonizes morphine analgesia in periaqueductal gray of the rat
Brain Res.
Anterior insular cortex anticipates impending stimulus significance
Neuroimage
Pro-nociceptive action of cholecystokinin in the periaqueductal grey: a role in neuropathic and anxiety-induced hyperalgesic states
Neurosci. Biobehav. Rev.
Prospective study on the relationship between depressive symptoms and chronic musculoskeletal pain
Pain
A possible neural basis for stress-induced hyperalgesia
Pain
Central representation of cold-evoked pain relief in capsaicin induced pain: an event-related fMRI study
Pain
Neural correlates of individual differences in pain-related fear and anxiety
Pain
An insular view of anxiety
Biol. Psychiatry
Contributions of the amygdala to emotion processing: from animal models to human behavior
Neuron
Can cognitive processes be inferred from neuroimaging data?
Trends Cogn. Sci.
Interoceptive awareness mediates the relationship between anxiety and the intensity of unpleasant feelings
J. Anxiety Disord.
Chronic pain and medullary descending facilitation
Trends Neurosci.
Pain-related emotions modulate experimental pain perception and autonomic responses
Pain
Anxiety sensitivity, anxiety frequency and the prediction of fearfulness
Behav. Res. Ther.
Fear and anxiety: divergent effects on human pain thresholds
Pain
Gender differences in pain: do emotions play a role?
Gend. Med.
Emotional modulation of spinal nociception and pain: the impact of predictable noxious stimulation
Pain
Emotional control of nociceptive reactions (ECON): do affective valence and arousal play a role?
Pain
Anxiety disorders and comorbid medical illness
Gen. Hosp. Psychiatry
Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated specific subsystems
J. Neurosci.
Cited by (448)
The effect of adverse employment circumstances on physical pain: Evidence from Australian panel data
2023, Preventive MedicineProsocial behaviour helps to ease physical pain: Longitudinal evidence from Britain
2023, Journal of Psychosomatic ResearchIn-person cognitive behavioural therapy vs. usual care after surgical management of extremity fractures: an unsuccessful feasibility trial
2024, Pilot and Feasibility Studies