title: Advancing our understanding of the mechanisms and mediators underlying pain and inflammation.
abstract: The inflammation process underlying rheumatic diseases is a complex cascade of events that involves several mediators, leading to a chronic condition of pain and correlated symptoms that affect the quality of life. As opposed to physiological pain, inflammatory pain arises from tissue damage via the sensitization of pain receptors (nociceptors). Sensitization leads to a lowering of the threshold for activation of nociceptors and an increase in the pain response to a given stimulus, and can occur at both a peripheral and central level. Following peripheral trauma or injury, inflammatory mediators such as phospholipase A(2) are upregulated, inducing the release of arachidonic acid, which is then converted to prostanoids such as prostaglandin E(2) (PGE(2)) via the action of the enzyme cyclo-oxygenase (COX)-2. PGE(2), the most abundant prostanoid found in injured tissue, is believed to be the principal mediator of hypersensitivity and is implicated in the processes of primary and secondary hyperalgesia. At a peripheral level, PGE(2) interacts with other inflammatory mediators to sensitize the peripheral terminals of the primary afferent nociceptors (primary hyperalgesia). In addition to its effect on peripheral pain, at a central level PGE(2) enhances excitatory glutaminergic transmission and downregulates inhibitory glycinergic transmission through the blockade of a glycine receptor subtype (GlyR α-3). These central mechanisms play an important role in the increase of pain sensitivity following inflammation and are responsible for the development of secondary hyperalgesia to regions beyond the injured tissue. Understanding the physiological mechanisms of inflammatory pain as well as preventing peripheral and central prostanoids production are important steps forward when considering the symptomatic treatment of patients with rheumatic conditions.
authors: Department of Physiology and Pathophysiology, University of Erlangen/Nürnberg, 91054, Erlangen, Germany. handwerker@physiologie1.uni-erlangen.de
authors: Hermann O
authors: HO
authors: Handwerker
mesh_terms: D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*
chemical_list: D018836:Inflammation Mediators
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