Pain is a powerful motivator of behavior and it is more than the perception of nociceptive
input. It is a complex experience that comprises different components: sensory
discriminative, emotional-motivational and cognitive components. In chronic pain, a negative
hedonic shift has been proposed that is characterized by disproportionally increased
emotional-motivational compared to sensory-discriminative pain components. Such a negative
hedonic shift is mirrored in a high comorbidity of chronic pain with affective disorders like
depression and anxiety. However, the neurobiological mechanisms underlying such a negative
hedonic shift i remain elusive. Animal work suggests an involvement of neuroinflammation,
caused by chronic pain, which in turn is related to impaired release of the neurotransmitter
dopamine. In line with this observation, impaired dopamine functioning has been described in
chronic pain. Importantly, dopamine acts also as a neuromodulator, regulating functional
connectivity between brain regions. Therefore, dysfunctional dopamine in chronic pain,
possibly caused by neuroinflammation, might lead to altered functional connectivity.
Correspondingly, altered functional connectivity in fronto-striatal brain networks has been
shown to be predictive of transition from subacute to chronic pain. The aim of this study is
to investigate the psychobiological mechanisms underlying the negative hedonic shift in
chronic pain with a focus on the causal role of neuroinflammation (substudy 1) and the role
of dopamine (substudy 2) in functional connectivity of fronto-striatal brain networks and
their relation to heightened emotional-motivational pain processing.