Pain perception in relation to emotional learning
Introduction
The role of the cortex in human pain perception remained controversial until the advent of noninvasive brain imaging technologies. Over the past 15 years solid evidence was generated indicating that multiple cortical and subcortical structures are involved in human pain perception [1•, 2]. The general assumption from the studies performed in healthy subjects and studying primarily pain after acute, experimental stimuli is the notion that the activation of a fixed set of brain structures evoke this percept, and that clinical pains must be due to small variations in the details of activations across these elements. More recent studies have emphasized the active role of the cortex in clinical, primarily chronic, pain conditions, and suggest that distinct chronic pains may have unique associated brain activity, reorganize the brain in unique ways, and also impact modulation of information processing in specific ways. The brain circuitry interfacing acute pain representation and diverse chronic pain conditions involves areas commonly thought to be essential in emotional learning and memory, and in reward and addictive behavior. This evidence is reviewed from the viewpoint of new insights regarding the role of reward circuitry and related behavior in pain perception, especially in clinical conditions.
Section snippets
Perceptual dimensions and types of pain
The definition of pain segregates it in two dimensions: an unpleasant sensory and emotional experience associated with actual or potential damage, or described in terms of such damage. As the threat for damage has negative survival connotations, perception of pain is always accompanied by negative emotions. Moreover, pain has a strong attentional tone; motor responses (pain leads to escape related reflexes); and autonomic/homeostatic responses. Classically, pain representation in the brain is
Cortical and subcortical circuitry for acute pain
The two brain structures most consistently activated in acute pain studies are the insula (INS) and anterior cingulate (ACC), while subcortically the most consistent activations are seen in the thalamus (TH) and basal ganglion (BG) [1•]. This activity pattern already suggests that pathways outside of the spinothalamic inputs are involved in acute pain since at least the activations in BG must be mediated through a separate nociceptive pathway [8]. Additional activity is observed in multiple
Cortical and subcortical circuitry for chronic pain
It can be asserted that there is increased activation of prefrontal cortical regions (PFCs) in clinical chronic pain conditions [1•], which in and of itself implies that chronic pain distorts cognitive and emotional perception/processing of everyday experiences, and is consistent with the vast clinical data indicating that such patients usually suffer from elevated anxiety and depression, and decreased quality of life. Chronic pain, defined as pain persisting past the healing process is
Chronic pain and brain atrophy
Contrasting brain metabolites between CBP and healthy subjects shows that N-acetyl-aspartate is diminished in multiple prefrontal regions in these patients [22], implying brain atrophy by decreased neural density in those regions. When this idea was directly tested using automated morphometry we were able to show that dorsolateral prefrontal cortex (DLPFC) and TH exhibit decreased gray matter density, and that these decreases were related to the duration and severity of CBP [23•]. Following
Supraspinal reorganization in chronic pain: evidence from animal studies
Recent animal studies show that cortical manipulations can modulate pain behavior [29, 30, 31, 32, 33]. Results emphasize the role of the INS, ACC, mPFC, and amygdala in pain, limbic structures with strong interconnectivity. Particularly relevant is the study by Johansen and Fields [30] demonstrating that ACC/mPFC activity is necessary and sufficient for noxious stimuli to produce an aversive memory, via a glutamate-mediated neuronal activation.
Pain and emotional learning and memory are intimately related, and chronic pain can be defined in this context
Chronic pain is defined as a state of continued suffering, sustained long after the initial inciting injury has healed. In terms of learning and memory one could recast this definition as: Chronic pain is a persistence of the memory of pain and/or the inability to extinguish the memory of pain evoked by an initial inciting injury. From this viewpoint the peripheral afferent barrage can be considered as part of the inciting event and the central representation/reorganization/sensitization as the
Conclusions
The above discussion suggests that the definition of chronic pain should be modified to incorporate the active role of the cortex and its reorganization, rendering such conditions at least partly a neurodegenerative disease. The cortical reorganization seems to impinge mainly on circuitry involved in emotional learning and memory; as such this circuitry must be considered part of the definition of chronic pain.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
The author thanks all the patients and volunteers who have contributed to the science we have generated over the last decade or so, as well as all the students and collaborating colleagues. This work was supported by NIH NINDS grants NS35115, NS53602, and NS57704.
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