Cancer-induced anorexia and malaise are mediated by CGRP neurons in the parabrachial nucleus

Anorexia is a common manifestation of chronic diseases, including cancer. Here we investigate the contribution to cancer anorexia made by calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) that transmit anorexic signals. We show that CGRP(PBN) neurons are activated in mice implanted with Lewis lung carcinoma cells. Inactivation of CGRP(PBN) neurons before tumor implantation prevents anorexia and loss of lean mass, and their inhibition after symptom onset reverses anorexia. CGRP(PBN) neurons are also activated in Apc(min/+) mice, which develop intestinal cancer and lose weight despite the absence of reduced food intake. Inactivation of CGRP(PBN) neurons in Apc(min/+) mice permits hyperphagia that counteracts weight loss, revealing a role for these neurons in a 'nonanorexic' cancer model. We also demonstrate that inactivation of CGRP(PBN) neurons prevents lethargy, anxiety and malaise associated with cancer. These findings establish CGRP(PBN) neurons as key mediators of cancer-induced appetite suppression and associated behavioral changes.