Prostaglandin E2 increases the proportion of neonatal rat dorsal root ganglion neurons that respond to bradykinin

C. L. Stucky, S. A. Thayer, V. S. Seybold

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35 Scopus citations

Abstract

Prostaglandins sensitize some nociceptors to noxious mechanical, thermal and chemical stimuli; however, not all nociceptors are sensitized by prostaglandins. We used cultures of dorsal root ganglion neurons from neonatal rats to determine whether prostaglandins differentially after the responsiveness of populations of neurons to the chemical stimulus bradykinin. Groups of dorsal root ganglion neurons were defined by size of the cell soma and by the presence of immunoreactivity for substance P. An increase in the concentration of free intracellular Ca2+ was used as an indicator of responsiveness to bradykinin. Pretreatment (5 min) with prostaglandin E2 (100 nM) increased the proportion of intermediate-size neurons (small areas of 240-320 μm2) that responded to 30 nM bradykinin by two-fold but did not alter the proportion of small-size neurons (somal areas of 160-239 μm2) that responded. Pretreatment with prostaglandin E2 had no effect on the maximum increase in free intracellular Ca2+ evoked by 30 nM bradykinin in either population of neurons, defined by size. Although pretreatment with PGE2, did not increase the proportion of intermediate-size neurons that responded to a lower concentration of bradykinin (3 nM), it did increase the concentration of free intracellular Ca2+ evoked by 3 nM bradykinin. Both results were consistent with a leftward shift in the stimulus-response relationship for bradykinin following pretreatment with PGE2. Small- and intermediate-size neurons that responded to bradykinin also differed in their expression of immunoreactivity for substance P. Furthermore, intermediate-size neurons that expressed immunoreactivity for substance P were more likely to respond to bradykinin after treatment with prostaglandin E2. These results support the hypothesis that prostaglandin E2 sensitizes some normally unresponsive primary afferent neurons to chemical stimuli. One population of neurons which becomes responsive to bradykinin after treatment with prostaglandin E2 can be defined based on cell size, and furthermore, these neurons are likely to express substance P. During inflammation, recruitment of primary afferent neurons that are immunoreactive for substance P would enhance the participation of substance P in central mechanisms that contribute to hyperalgesia.

Original languageEnglish (US)
Pages (from-to)1111-1123
Number of pages13
JournalNeuroscience
Volume74
Issue number4
DOIs
StatePublished - Oct 1996

Keywords

  • Bradykinin
  • Dorsal root
  • Ganglion neurons
  • Prostaglandin E
  • Senzitization
  • Substance P

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