<p>The afferent matrix (peripheral nerve fibers and central processing) provides the brain with information regarding processes occurring at the surface of the skin, in the musculoskeletal system, and in the organs. Nerve fibers encoding tissue-damaging stimuli and events—the nociceptors—comprise an important information channel of this matrix. Nociceptors are not only activated by damaging stimuli but also sensitized by them. Nociceptors contain specific ion channels that can be opened in response to mechanical, thermal, and chemical stimuli. The thereby-induced depolarization leads to generation of action potentials via the opening of voltage-gated sodium channels. Moreover, nociceptors possess metabotropic receptors to which ligands (e.g., inflammatory mediators) can bind. This activates intracellular molecular signaling pathways in the nociceptor, which can render the ion channels more sensitive. This is the foundation of sensitization in the case of inflammatory diseases. Via this route, numerous immune mediators (e.g., cytokines), nerve growth factor, antigen–antibody complexes, pathogens (pathogen-associated molecular patterns), and degradation products released from damaged cells (damage-associated molecular patterns) lead to sensitization of nociceptors. Some mediators, e.g., opioids, inhibit this sensitization. In addition to their sensory functions, many nociceptors also have a secretory function. Upon depolarization they release neuropeptides such as substance&#xa0;P and calcitonin gene-related peptide into the tissue, which act on blood vessels and local inflammatory cells to influence blood supply and local inflammatory processes. This neurogenic inflammation can promote inflammatory processes, but it likely also stimulates recovery processes.</p>