title: Microglial GRK2: a novel regulator of transition from acute to chronic pain.
abstract: Pain is a hallmark of tissue damage and inflammation promoting tissue protection and thereby contributing to repair. Therefore, transient acute pain is an important feature of the adaptive response to damage. However, in a significant number of cases, pain persists for months to years after the problem that originally caused the pain has resolved. Such chronic pain is maladaptive as it no longer serves a protective aim. Chronic pain is debilitating, both physiologically and psychologically, and treatments to provide relief from chronic pain are often ineffective. The neurobiological mechanisms underlying the transition from adaptive acute pain to maladaptive chronic pain are only partially understood. In this review, we will summarize recent evidence that a kinase known as G protein-coupled receptor kinase (GRK2) is a key regulator of the transition from acute to chronic inflammatory pain. Our recent studies have shown that mice with a reduction in the cellular level of GRK2 develop chronic hyperalgesia in response to inflammatory mediators that induce only transient hyperalgesia in WT mice. This finding is clinically relevant because rodent models of chronic pain are associated with reduced cellular levels of GRK2. We propose that GRK2 is a newly discovered major player in the regulation of chronic pain. The pathways regulated by this kinase may open up new avenues for development of treatment strategies that target the cause, and not the symptoms of chronic pain.
authors.affiliation: Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands. A.Kavelaars@umcutrecht.nl
authors.forename: Annemieke
authors.initials: A
authors.lastname: Kavelaars
authors.forename: Niels
authors.initials: N
authors.lastname: Eijkelkamp
authors.forename: Hanneke L D M
authors.initials: HL
authors.lastname: Willemen
authors.forename: Huijing
authors.initials: H
authors.lastname: Wang
authors.forename: Anibal Garza
authors.initials: AG
authors.lastname: Carbajal
authors.forename: Cobi J
authors.initials: CJ
authors.lastname: Heijnen
mesh_terms: D059787:Acute Pain / Q000201:enzymology / Q000503:physiopathology; D000818:Animals; D059350:Chronic Pain / Q000201:enzymology* / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005544:Forecasting; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006930:Hyperalgesia / Q000201:enzymology / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology*; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017628:Microglia / Q000201:enzymology* / Q000378:metabolism; D009437:Neuralgia / Q000201:enzymology* / Q000503:physiopathology; D017472:Receptors, Interleukin-1 / Q000502:physiology; D012584:Sciatic Nerve / Q000293:injuries; D015398:Signal Transduction; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology; D013127:Spinal Nerves / Q000293:injuries
chemical_list: D016207:Cytokines; D017472:Receptors, Interleukin-1; C496567:GRK2 protein, human; C496568:GRK2 protein, mouse; D054769:G-Protein-Coupled Receptor Kinase 2