Chronic pain: the role of learning and brain plasticity

Abstract

Based on theoretical considerations and recent observations, we argue that continued suffering of chronic pain is critically dependent on the state of motivational and emotional mesolimbic-prefrontal circuitry of the brain. The plastic changes that occur within this circuitry in relation to nociceptive inputs dictate the transition to chronic pain, rendering the pain less somatic and more affective in nature. This theoretical construct is a strong departure from the traditional scientific view of pain, which has focused on encoding and representation of nociceptive signals. We argue that the definition of chronic pain can be recast, within the associative learning and valuation concept, as an inability to extinguish the associated memory trace, implying that supraspinal/cortical manipulations may be a more fruitful venue for adequately modulating suffering and related behavior for chronic pain. We briefly review the evidence generated to date for the proposed model and emphasize that the details of underlying mechanisms remain to be expounded.

Figure 1

A model regarding brain circuitry involved in the transition from acute to chronic pain. Nociceptive information, perhaps distorted by peripheral and spinal cord sensitization processes, impinges on limbic circuitry. The interaction of limbic circuitry with prefrontal processes determines the level at which a certain pain condition transitions to a more emotional state. The limbic circuitry also provides learning/modulation signals to the rest of the cortex inducing functional and anatomical distortions that reflect the suffering and coping strategies, adapted from (Apkarian et al., 2011).

Figure 2

Brain activity meta-analysis maps derived from the Neurosynth tool (Yarkoni et al., 2011), for the four terms indicated. Only brain regions positively activated for each term are shown, with the appropriate color, when activity was thresholded at a z-value > 5.0. At this threshold, “emotion” activates mainly bilateral amygdala and medial prefrontal cortex; “memory” activates bilateral hippocampus and parts of the posterior parietal and lateral prefrontal regions; “reward” activates bilateral nucleus accumbens, hypothalamus, and ventral tegmentum; “pain” activates bilaterally anterior cingulate, thalamus, periaqueductal gray, and insula.