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Mechanisms of Pathologic Pain


Pain becomes pathological when it outlives its usefulness as an acute warning system. Understanding the mechanisms of transition from acute to chronic pain, from physiological to pathological pain, and from protective to harmful pain holds the key to effective prevention of chronic pain. Peripheral sensitization refers to a phenomenon, where sensory neurons develop spontaneous pathological activity, unusual excitability, and augmented sensitivity to chemical, thermal, and mechanical stimuli after a peripheral nerve insult or lesion. Central sensitization is a result of neuroplasticity in the central nervous system. Increased volley of afferent input from nociceptors can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in nociceptive pathways. The processes of neuroplasticity involve activation of inflammatory cells, such as macrophages (and microglia in the spinal cord), mast cells, platelets, endothelial cells, fibroblast, and other immune cells, and release of inflammatory mediators such as cytokines, chemokines, and a host of other mediators. Interactions of these mediators with specific receptors in the nociceptors or the spinal cord neurons may lead to phosphorylation or changes in expression of ion channels, receptors, transporters, and other effectors through specific signaling pathways and change the excitability, conductivity, and transmissibility of pain processing pathways. In addition, other mechanisms may include sprouting of afferent fibers in the spinal cord, changes in descending inhibitory/excitatory pathways, and reorganization of the cortical areas and their interconnections.


  • Pathologic pain
  • Peripheral sensitization
  • Central sensitization
  • Pain windup
  • Spinal cord dorsal horn
  • Nociceptors
  • Cytokines
  • Chemokines
  • Inflammatory cells
  • Immune cells
  • Ion channels
  • Receptors

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Suggested Reading

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Correspondence to Jianguo Cheng MD, PhD .

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Cheng, J. (2018). Mechanisms of Pathologic Pain. In: Cheng, J., Rosenquist, R. (eds) Fundamentals of Pain Medicine. Springer, Cham.

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