The peripheral nervous system is connected with lymphoid organs through sensory nerves that mediate pain reflexes and may influence immune responses through the release of neuropeptides such as calcitonin gene-related peptide (CGRP). Local and systemic levels of CGRP increase rapidly during inflammatory responses. CGRP inhibits effector functions of various immune cells and dampens inflammation by distinct pathways involving the amplification of IL-10 production and/or the induction of the transcriptional repressor inducible cAMP early repressor (ICER). Thus, available evidence suggests that, in neuro-immunological interactions, CGRP mediates a potent peptidergic anti-inflammatory pathway.