Prostaglandin E 2 in the medial preoptic area produces hyperalgesia and activates pain-modulating circuitry in the rostral ventromedial medulla

M. M. Heinricher, M. J. Neubert, M. E. Martenson, L. Gonçalves

Research output: Contribution to journalArticle

25 Scopus citations


Prostaglandin E 2 (PGE 2) produced in the medial preoptic region (MPO) in response to immune signals is generally accepted to play a major role in triggering the illness response, a complex of physiological and behavioral changes induced by infection or injury. Hyperalgesia is now thought to be an important component of the illness response, yet the specific mechanisms through which the MPO acts to facilitate nociception have not been established. However, the MPO does project to the rostral ventromedial medulla (RVM), a region with a well-documented role in pain modulation, both directly and indirectly via the periaqueductal gray. To test whether PGE 2 in the MPO produces thermal hyperalgesia by recruiting nociceptive modulating neurons in the RVM, we recorded the effects of focal application of PGE 2 in the MPO on paw withdrawal latency and activity of identified nociceptive modulating neurons in the RVM of lightly anesthetized rats. Microinjection of a sub-pyrogenic dose of PGE 2 (50 fg in 200 nl) into the MPO produced thermal hyperalgesia, as measured by a significant decrease in paw withdrawal latency. In animals displaying behavioral hyperalgesia, the PGE 2 microinjection activated on-cells, RVM neurons thought to facilitate nociception, and suppressed the firing of off-cells, RVM neurons believed to have an inhibitory effect on nociception. A large body of evidence has implicated prostaglandins in the MPO in generation of the illness response, especially fever. The present study indicates that the MPO also contributes to the hyperalgesic component of the illness response, most likely by recruiting the nociceptive modulating circuitry of the RVM.

Original languageEnglish (US)
Pages (from-to)389-398
Number of pages10
Issue number2
StatePublished - Sep 21 2004



  • extracellular single-unit recording
  • hyperalgesia
  • illness response
  • microinjection
  • pain modulation
  • raphe

ASJC Scopus subject areas

  • Neuroscience(all)

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