Persistent Hyperalgesia and Cytokines

  • Sergio H. Ferreira
  • Daniela Sachs
  • Fernando Q. Cunha
  • B. B. Lorenzetti


Inflammatory hyperalgesia is the common denominator of all types of inflammatory pain. Hyperalgesia involves an integrated process that results in the functional up-regulation of the primary sensory neuron. In this circumstance, stimuli which in a normal tissue have little or no effect now activate the nociceptors to induce overt behavioural responses in experimental animals and overt pain in man. Depending upon the inflammatory stimulus and the duration of the plateau of hyperalgesia, the hyperalgesia may be classified as immediate, delayed or persistent. Persistent hyperalgesia is induced by successive daily injections of a hyperalgesic stimulus which causes delayed hyperalgesia. After 6–9 daily injections the sensitivity of the nociceptor does not return to its basal level but, instead, reaches a plateau. If this hyperalgesic plateau is maintained for 7-9 days, by additional daily injections, it persists (in the absence of further injections) for more than thirty days. These observations regarding persistent hyperalgesia indicate an important role for the sensitization of the primary sensory neuron in the establishment of chronic pain and point to the importance of using effective doses of peripherally acting analgesics during the treatment of inflammatory states of long duration. The prevention of a long lasting hyperalgesic state is crucial in order to avoid the development of persistent hyperalgesia. Once the persistent hyperalgesic state is established, cyclo-oxygenase inhibitors are ineffective and the only analgesics able to inhibit the ongoing hyperalgesia are analgesics with other mechanisms of action.

Key words

Persistent pain Primary sensory neuron Cytokines Prostaglandins 


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Copyright information

© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Sergio H. Ferreira
    • 1
  • Daniela Sachs
    • 1
  • Fernando Q. Cunha
    • 1
  • B. B. Lorenzetti
    • 2
  1. 1.Department of Pharmacology, Faculty of Medicine of Ribeirão PretoUniversity of São PauloRibeirão Preto, São PauloBrazil
  2. 2.Department of PharmacologyUniversity Federal ParanáCuritiba, ParanáBrazil

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