Inflaming the brain: CRPS a model disease to understand neuroimmune interactions in chronic pain.

We review current concepts in CRPS from a neuroimaging perspective and point out topics and potential mechanisms that are suitable to be investigated in the next step towards understanding the pathophysiology of CRPS. We have outlined functional aspects of the syndrome, from initiating lesion via inflammatory mechanisms to CNS change and associated sickness behavior, with current evidence for up-regulation of immunological factors in CRPS, neuroimaging of systemic inflammation, and neuroimaging findings in CRPS. The initiation, maintenances and CNS targets implicated in CRPS and in the neuro-inflammatory reflex are discussed in terms of CRPS symptoms and recent preclinical studies. Potential avenues for investigating CRPS with PET and fMRI are described, along with roles of inflammation, treatment and behavior in CRPS. It is our hope that this outline will provoke discussion and promote further empirical studies on the interactions between central and peripheral inflammatory pathways manifest in CRPS.