Critical role of nociceptor plasticity in chronic pain.
The transition from acute to chronic pain states might be the most important challenge in research to improve clinical treatment of debilitating pain. We describe a recently identified mechanism of neuronal plasticity in primary afferent nociceptive nerve fibers (nociceptors) by which an acute inflammatory insult or environmental stressor can trigger long-lasting hypersensitivity of nociceptors to inflammatory cytokines. This phenomenon, "hyperalgesic priming," depends on the epsilon isoform of protein kinase C (PKCepsilon) and a switch in intracellular signaling pathways that mediate cytokine-induced nociceptor hyperexcitability. We discuss the impact of this discovery on our understanding of, and ultimately our ability to treat, a variety of enigmatic and debilitating pain conditions, including those associated with repetitive injury, and generalized pain conditions, such as fibromyalgia.
Department of Oral and Maxillofacial Surgery and Division of Neuroscience, University of California, San Francisco, CA 94143-0440, USA.
David B
DB
Reichling
Jon D
JD
Levine
D000818:Animals; D002908:Chronic Disease; D006801:Humans; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology; D007527:Isoenzymes / Q000378:metabolism; D008954:Models, Biological; D009473:Neuronal Plasticity / Q000502:physiology*; D009619:Nociceptors / Q000378:metabolism / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D013312:Stress, Physiological / Q000502:physiology; D014947:Wounds and Injuries / Q000503:physiopathology
D007527:Isoenzymes; D051744:Protein Kinase C-epsilon