Roles of the hippocampal formation in pain information processing

Pain is a complex experience consisting of sensory-discriminative, affective-motivational, and cognitive-evaluative dimensions. Now it has been gradually known that noxious information is processed by a widely-distributed, hierarchically-interconnected neural network, referred to as neuromatrix, in the brain. Thus, identifying the multiple neural networks subserving these functional aspects and harnessing this knowledge to manipulate the pain response in new and beneficial ways are challenging tasks. Albeit with elaborate research efforts on the cortical responses to painful stimuli or clinical pain, involvement of the hippocampal formation (HF) in pain is still a matter of controversy. Here, we integrate previous animal and human studies from the viewpoint of HF and pain, sequentially representing anatomical, behavioral, electrophysiological, molecular/biochemical and functional imaging evidence supporting the role of HF in pain processing. At last, we further expound on the relationship between pain and memory and present some unresolved issues.