Exacerbation of tonic but not phasic pain by entorhinal cortex lesions.

The hippocampus is actively involved in pain modulation. Previous studies have shown that inhibition, resection or pharmacological interference of the hippocampus or its subcortical afferent sources such as the medial septum and amygdala produce anti-nociceptive effects. But how the cortical connections of the hippocampus modulate pain remains unexplored. The entorhinal cortex (EC) constitutes the major gateway between the hippocampus and the neocortex. In the present study, rats with medial (MEC), lateral (LEC) or sham EC lesions and received the hot plate and the intra-plantar formalin injection tests. Neither MEC nor LEC lesions affected the hot plate test and the first phase of the formalin test. In contrast, paw licking responses in the second phase of the formalin test significantly increased with both MEC and LEC lesions. These results suggested that that the hippocampal-cortical interactions channeled by the EC were involved in tonic but not phasic pain conditions, and that cortical and sub-cortical connections of the hippocampus played independent roles in pain modulation.