Acute inflammation in the joint: Its control by the sympathetic nervous system and by neuroendocrine systems

Abstract

Inflammation of tissues is under neural control involving neuroendocrine, sympathetic and central nervous systems. Here we used the acute experimental inflammatory model of bradykinin-induced plasma extravasation (BK-induced PE) of the rat knee joint to investigate the neural and neuroendocrine components controlling this inflammation. 1. BK-induced PE is largely dependent on the sympathetic innervation of the synovium, but not on activity in these neurons and not on release of norepinephrine. 2. BK-induced PE is under the control of the hypothalamo-pituitary-adrenal (HPA) system and the sympatho-adrenal (SA) system, activation of both leading to depression of BK-induced PE. The inhibitory effect of the HPA system is mediated by corticosterone and dependent on the sympathetic innervation of the synovium. The inhibitory effect of the SA system is mediated by epinephrine and β2-adrenoceptors. 3. BK-induced PE is inhibited during noxious stimulation of somatic or visceral tissues and is mediated by the neuroendocrine systems. The nociceptive-neuroendocrine reflex circuits are (for the SA system) spinal and spino-bulbo-spinal. 4. The nociceptive-neuroendocrine reflex circuits controlling BK-induced PE are under powerful inhibitory control of vagal afferent neurons innervating the defense line (connected to the gut-associated lymphoid tissue) of the gastrointestinal tract. This inhibitory link between the visceral defense line and the central mechanisms controlling inflammatory mechanisms in body tissues serves to co-ordinate protective defensive mechanisms of the body. 5. The circuits of the nociceptive-neuroendocrine reflexes are under control of the forebrain. In this way, the defensive mechanisms of inflammation in the body are co-ordinated, optimized, terminated as appropriate, and adapted to the behavior of the organism.