Reward Circuitry Plasticity in Pain Perception and Modulation

Abstract

Although pain is a widely known phenomenon and an important clinical symptom that occurs in numerous diseases, its mechanisms are still barely understood. Owing to the scarce information concerning its pathophysiology, particularly what is involved in the transition from an acute state to a chronic condition, pain treatment is frequently unsatisfactory, therefore contributing to the amplification of the chronic pain burden. In fact, pain is an extremely complex experience that demands the recruitment of an intricate set of central nervous system components. This includes cortical and subcortical areas involved in interpretation of the general characteristics of noxious stimuli. It also comprises neural circuits that process the motivational-affective dimension of pain. Hence, the reward circuitry represents a vital element for pain experience and modulation. This review article focuses on the interpretation of the extensive data available connecting the major components of the reward circuitry to pain suffering, including the nucleus accumbens, ventral tegmental area, and the medial prefrontal cortex; with especial attention dedicated to the evaluation of neuroplastic changes affecting these structures found in chronic pain syndromes, such as migraine, trigeminal neuropathic pain, chronic back pain, and fibromyalgia.

Keywords: chronic pain; migraine; nucleus accumbens; prefrontal cortex; reward circuitry.

FIGURE 1

Corticolimbic circuits and the main components of the reward circuitry are illustrated. Red lines: the nucleus accumbens (NAc) receives afferent nociceptive information mainly via connections with the anterior cingulate cortex (ACC), amygdala (Amy), thalamus, and parabrachial nucleus (PB). Possible direct connections from the spinal cord to the NAc (red dotted line) are also shown. Blue lines: corticostriatal projections arising from the prefrontal cortex (PFC) and ACC. The connections between the Amy, thalamus and ventral tegmental area (VTA) and the NAc are also represented by blue lines. The descending pathway from the NAc to the spinal cord, that putatively regulates nociceptive information, probably through the rostral ventromedial medulla (RVM), is represented by a gold dotted line. Adapted by permission from Macmillan Publishers Ltd: Nature Neuroscience (Navratilova and Porreca, 2014), copyright 2014.

FIGURE 2

Reduced μ-opioid receptor binding potential (μOR BPND) in Trigeminal Neuropathic Pain. Decreased μOR BPND in the left NAc in axial (A), sagittal (B), and coronal (C) planes (T = 3.2) (DosSantos et al., 2012b).

FIGURE 3

Migraine severity and ictal μ-opioid activation. (Left) Pain intensity and location in each migraine patient evaluated. (Center) 3D image representing the average rating of both the pain intensity and the pain location. (Right) Decreased μOR BPND in the mPFC during the migraine ictal phase as compared to the interictal phase (DaSilva et al., 2014).

FIGURE 4

Reduced μOR BPND related to transcranial direct current stimulation (tDCS). (Upper) μOR BPND during the baseline. (Lower) μOR BPND during anodal motor cortex tDCS in the ACC, NAc, and insula (DosSantos et al., 2012a).