Anterior insular volume decrease is associated with dysfunction of the reward system in patients with chronic pain

Chronification of pain is associated with both anatomical and functional alterations of the brain. Alteration in regional grey matter volume might potentially be associated with modified activity of specific brain networks. In this cross-sectional, observational study, we sought to identify brain regions with grey matter volume changes in patients with chronic pain and to reveal its significance by analysing alteration in functional connectivity from those regions. We further explored relevance of such alterations with psychometrics of chronic pain.

We recruited 23 patients with chronic pain and 17 age-, gender-matched healthy control subjects. After completing multiple psychophysical questionnaires, each subject underwent resting-state functional magnetic resonance imaging and three-dimensional anatomical imaging on a 3 Tesla magnetic resonance imaging scanner.

Patients with chronic pain showed significant volume decrease at the right anterior insular cortex (p < 0.001) and the left middle cingulate cortex (p < 0.001) compared with healthy controls. They also showed decreased connectivity between the right anterior insular cortex and the left nucleus accumbens in negative association with the Pain Catastrophizing Scale (R²  = 0.20, p = 0.046) and the Beck's Depression Inventory scores (R²  = 0.24, p = 0.017).

Decreased grey matter volumes of those core regions for affective processing of pain might be a common cerebral feature shared by, at least some of, different aetiologies of chronic pain. Dysfunctional network between the anterior insular cortex and the nucleus accumbens might reflect affective and motivational disability involved in chronic pain. Such anatomical and functional profiles could potentially be part of a cerebral signature for chronification of pain.

This article illustrates decreased network activity of the reward system in association with insular cortical volume decrease in patients with chronic pain, and its close relationships with affective and cognitive morbidity of pain. Attenuation of brain's reward system involving cortical plastic changes might have a key role in chronification of pain.