The Emotional Brain as a Predictor and Amplifier of Chronic Pain

Abstract

Human neuroimaging studies and complementary animal experiments now identify the gross elements of the brain involved in the chronification of pain. We briefly review these advances in relation to somatic and orofacial persistent pain conditions. First, we emphasize the importance of reverse translational research for understanding chronic pain-that is, the power of deriving hypotheses directly from human brain imaging of clinical conditions that can be invasively and mechanistically studied in animal models. We then review recent findings demonstrating the importance of the emotional brain (i.e., the corticolimbic system) in the modulation of acute pain and in the prediction and amplification of chronic pain, contrasting this evidence with recent findings regarding the role of central sensitization in pain chronification, especially for orofacial pain. We next elaborate on the corticolimbic circuitry and underlying mechanisms that determine the transition to chronic pain. Given this knowledge, we advance a new mechanistic definition of chronic pain and discuss the clinical implications of this new definition as well as novel therapeutic potentials suggested by these advances.

Altered Hypothalamic Region Covariance in Migraine and Cluster Headache: A Structural MRI Study

“…14 Weakened hypothalamic connections in patients with migraine and CH might suggest a dysfunction/ disconnection to the pain control/modulatory systems 25 and contribute to the notion that alterations in the corticolimbic circuitry might contribute to pain chronification. 37,38 Although the main focus of this study was to better understand how the hypothalamic covariance patterns that are present in HC are altered or "weakened" in patients with migraine and in patients with CH, it is noteworthy that the within-group analyses in migraine patients and CH patients showed significant structural covariance patterns that were not found in the healthy control cohort.…”

“…Weakened hypothalamic connections in patients with migraine and CH might suggest a dysfunction/disconnection to the pain control/modulatory systems and contribute to the notion that alterations in the corticolimbic circuitry might contribute to pain chronification …”

Cortical arousal in children and adolescents with functional neurological symptoms during the auditory oddball task

“…In the resting state, subjective pain is associated with increases in activation in the amygdala, insula and medial prefrontal cortex (Apkarian et al, 2011, Vachon-Presseau et al, 2016). The medial prefrontal cortex encodes both the intensity of subjective pain (Apkarian et al, 2011, Vachon-Presseau et al, 2016) and it modulates cardiovascular responses (Gianaros et al, 2004). Our finding of a correlation between pain and heart rate may be reflective this overlap of functions within the medial prefrontal cortex.…”

Emerging Targets for the Management of Osteoarthritis Pain

“…Since many of the pathways described above can be selectively and potently targeted, they offer an exciting opportunity for analgesic drug development. However, it should be realized that OA is a multifactorial chronic disease, and human brain imaging studies are increasingly uncovering the complex networks of sensory and emotional experiences that underlie chronic pain [84]. Therefore, a final description of OA pain will presumably involve integration of peripheral and central components at all levels of the neuraxis.…”