Neurochemical Research

, Volume 33, Issue 10, pp 1970–1978 | Cite as

Intracellular Signaling in Primary Sensory Neurons and Persistent Pain

  • Jen-Kun Cheng
  • Ru-Rong JiEmail author
Original Paper


During evolution, living organisms develop a specialized apparatus called nociceptors to sense their environment and avoid hazardous situations. Intense stimulation of high threshold C- and Aδ-fibers of nociceptive primary sensory neurons will elicit pain, which is acute and protective under normal conditions. A further evolution of the early pain system results in the development of nociceptor sensitization under injury or disease conditions, leading to enhanced pain states. This sensitization in the peripheral nervous system is also called peripheral sensitization, as compared to its counterpart, central sensitization. Inflammatory mediators such as proinflammatory cytokines (TNF-α, IL-1β), PGE2, bradykinin, and NGF increase the sensitivity and excitability of nociceptors by enhancing the activity of pronociceptive receptors and ion channels (e.g., TRPV1 and Nav1.8). We will review the evidence demonstrating that activation of multiple intracellular signal pathways such as MAPK pathways in primary sensory neurons results in the induction and maintenance of peripheral sensitization and produces persistent pain. Targeting the critical signaling pathways in the periphery will tackle pain at the source.


Peripheral sensitization Dorsal root ganglion Inflammatory pain Neuropathic pain MAP kinases Neural plasticity 



This study was funded by NIH grants DE17794, NS54932, and TW7180 (RRJ) and Bonica Fellowship from International Association for the Study of Pain (JKC).


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Department of Anesthesiology, Pain Research CenterBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  2. 2.Department of AnesthesiologyMackay Memorial HospitalTaipeiTaiwan

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