Since Elie Mechnikoff discovered the main principles of local acute phase reaction (APR), many new regularities of the development of both local and systemic inflammatory responses have been found. The time has come to examine anew the neurohumoral mechanisms of APR and especially those central and peripheral mechanisms that provide the formation of nociceptive responses aimed at maintaining homeostasis and surviving under unfavourable factors. The review analyses the neurohumoral mechanisms of nociceptive response generation in the course of APR.