Critical role of nociceptor plasticity in chronic pain

Trends Neurosci. 2009 Dec;32(12):611-8. doi: 10.1016/j.tins.2009.07.007. Epub 2009 Sep 24.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Chronic Disease
  • Humans
  • Hyperalgesia / metabolism
  • Hyperalgesia / physiopathology
  • Isoenzymes / metabolism
  • Models, Biological
  • Neuronal Plasticity / physiology*
  • Nociceptors / metabolism
  • Nociceptors / physiology*
  • Pain / physiopathology*
  • Protein Kinase C-epsilon / metabolism
  • Stress, Physiological / physiology
  • Wounds and Injuries / physiopathology


  • Isoenzymes
  • Protein Kinase C-epsilon