Endogenous prolactin generated during peripheral inflammation contributes to thermal hyperalgesia

Phoebe E. Scotland, Mayur Patil, Sergei Belugin, Michael A. Henry, Vincent Goffin, Kenneth M. Hargreaves, Armen N. Akopian

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Prolactin (PRL) is a hormone and a neuromodulator. It sensitizes TRPV1 (transient receptor potential cation channel subfamily V member 1) responses in sensory neurons, but it is not clear whether peripheral inflammation results in the release of endogenous PRL, or whether endogenous PRL is capable of acting as an inflammatory mediator in a sex-dependent manner. To address these questions, we examined inflammation-induced release of endogenous PRL, and its regulation of thermal hyperalgesia in female and male rats. PRL is expressed in several types of peripheral neuronal and non-neuronal cells, including TRPV1-positive nerve fibers, preadipocytes and activated macrophages/monocytes localized in the vicinity of nerves. Evaluation of PRL levels in hindpaws and plasma indicated that complete Freund's adjuvant (CFA) stimulates release of peripheral, but not systemic, PRL within 6-48h in both ovariectomized females with estradiol replacement (OVX-E) and intact male rats. The time course of release varies in OVX-E and intact male rats. We next employed the prolactin receptor (PRL-R) antagonist Δ1-9-G129R-hPRL to assess the role of locally produced PRL in nociception. Applied at a ratio of 1:1 (PRL:Δ1-9-G129R-hPRL; 40nm each), this antagonist was able to nearly (≈80%) reverse PRL-induced sensitization of capsaicin responses in rat sensory neurons. CFA-induced inflammatory thermal hyperalgesia in OVX-E rat hindpaws was significantly reduced in a dose-dependent manner by the PRL-R antagonist at 6h but not at 24h. In contrast, PRL contributed to inflammatory thermal hyperalgesia in intact male rats at 24, but not at 6h. These findings indicate that inflammation leads to accumulation of endogenous PRL in female and male rats. Furthermore, PRL acts as an inflammatory mediator at different time points for female and intact male rats.

Original languageEnglish (US)
Pages (from-to)745-754
Number of pages10
JournalEuropean Journal of Neuroscience
Volume34
Issue number5
DOIs
StatePublished - Sep 1 2011

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Keywords

  • Inflammation
  • Prolactin
  • Prolactin antagonist
  • Rat
  • Sensory neurons
  • TRPV1

ASJC Scopus subject areas

  • Neuroscience(all)

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