Isoprostanes, novel eicosanoids that produce nociception and sensitize rat sensory neurons

Angela R. Evans, Heidi Junger, Michael D. Southall, Grant Nicol, Linda S. Sorkin, James T. Broome, Timothy W. Bailey, Michael Vasko

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Isoprostanes are a novel class of eicosanoids primarily formed by peroxidation of arachidonic acid. Because of their potential as inflammatory and/or hyperalgesic agents whose formation is largely independent of cyclooxygenases, we examined whether 8-iso prostaglandin E2 (8-iso PGE2) or 8-iso prostaglandin F(2α) (8-iso PGF(2α)) reduces mechanical and thermal withdrawal threshold in rats, and whether they sensitize rat sensory neurons. Injection of 1 μg of 8-iso PGE2 (in 2.5 μl) into the hindpaw of rats significantly reduced mechanical and thermal withdrawal thresholds, whereas 1 μg of 8-iso PGF(2α) elicited a transient decrease in only the mechanical withdrawal threshold. Both isoprostanes enhanced the firing of C-nociceptors in a concentration-dependent manner when injected into peripheral receptive fields. Exposing sensory neurons grown in culture to 1 μM 8-iso PGE2 or 8- iso PGF(2α) augmented the number of action potentials elicited by a ramp of depolarizing current. In contrast, 8-iso PGE2 but not 8-iso PGF(2α) enhanced the release of substance P- and calcitonin gene-related peptide-like immunoreactivity from isolated sensory neurons. Ten micromolar 8-iso PGE2 stimulated peptide release directly, whereas treatment with 1 μM 8-iso PGE2 augmented the release evoked by either bradykinin or capsaicin. Pretreating neuronal cultures with the nonsteroidal anti-inflammatory drug ketorolac did not alter the sensitizing action of 8-iso PGE2 on peptide release, suggesting that this action of the isoprostane was not secondary to the production of prostaglandins via the cyclooxygenase pathway. These data support the notion that isoprostanes are an important class of inflammatory mediators that augment nociception.

Original languageEnglish
Pages (from-to)912-920
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume293
Issue number3
StatePublished - Jun 2000

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Isoprostanes
Nociception
Eicosanoids
Sensory Receptor Cells
Dinoprostone
Prostaglandins F
Prostaglandin-Endoperoxide Synthases
Hot Temperature
Ketorolac
Nociceptors
Peptides
Architectural Accessibility
Calcitonin Gene-Related Peptide
Capsaicin
Bradykinin
Substance P
Arachidonic Acid
Action Potentials
Anti-Inflammatory Agents
Injections

ASJC Scopus subject areas

  • Pharmacology

Cite this

Isoprostanes, novel eicosanoids that produce nociception and sensitize rat sensory neurons. / Evans, Angela R.; Junger, Heidi; Southall, Michael D.; Nicol, Grant; Sorkin, Linda S.; Broome, James T.; Bailey, Timothy W.; Vasko, Michael.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 293, No. 3, 06.2000, p. 912-920.

Research output: Contribution to journalArticle

Evans, AR, Junger, H, Southall, MD, Nicol, G, Sorkin, LS, Broome, JT, Bailey, TW & Vasko, M 2000, 'Isoprostanes, novel eicosanoids that produce nociception and sensitize rat sensory neurons', Journal of Pharmacology and Experimental Therapeutics, vol. 293, no. 3, pp. 912-920.
Evans, Angela R. ; Junger, Heidi ; Southall, Michael D. ; Nicol, Grant ; Sorkin, Linda S. ; Broome, James T. ; Bailey, Timothy W. ; Vasko, Michael. / Isoprostanes, novel eicosanoids that produce nociception and sensitize rat sensory neurons. In: Journal of Pharmacology and Experimental Therapeutics. 2000 ; Vol. 293, No. 3. pp. 912-920.
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