Crosstalk between the nociceptive and immune systems in host defence and disease

Nociceptors can be activated and eventually sensitized by several pro-inflammatory mediators, including cytokines and chemokines. These mediators cause profound changes in sensory neurons, including mobilization of intracellular calcium, an increase in voltage- or ligand-gated channel expression or function, and alteration of the cellular transcriptional profile.The role of autoantibodies is increasingly being recognized in persistent pain states. Some autoantibodies trigger inflammation and have destructive effects within the sensory nervous system — for instance, neuromyelitis optica and Guillain–Barré syndrome. Some autoantibodies may alter the functional status of the somatosensory system, such as antibodies directed against voltage-gated potassium channel complexes.Nociceptors can affect vascular permeability and modulate the phenotype of immune cells through the release of neuropeptides (such as calcitonin gene-related peptide or substance P) or potentially via the other mediators that are readily released upon activation.Several studies suggest that the interactions between nociceptors and immune cells may have a role in the pathogenesis of several immune-mediated diseases, including arthritis, colitis and psoriasis, as well as upon infection. As a proof of concept, chemical disruption or genetic ablation of nociceptors has a drastic impact on the onset, severity and resolution of several pathological conditions in vivo. Similar conclusions have been suggested by clinical reports.