Regulation of Expression of Hyperalgesic Priming by Estrogen Receptor α in the Rat

Luiz F Ferrari; Dionéia Araldi; Jon D Levine

doi:10.1016/j.jpain.2016.12.017

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Regulation of Expression of Hyperalgesic Priming by Estrogen Receptor α in the Rat

Journal article

Peer reviewed

Regulation of Expression of Hyperalgesic Priming by Estrogen Receptor α in the Rat

Luiz F Ferrari, Dionéia Araldi and Jon D Levine

The journal of pain, Vol.18(5), pp.574-582

05/01/2017

DOI: 10.1016/j.jpain.2016.12.017

PMID: 28089711

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Abstract

Hyperalgesic priming, a sexually dimorphic model of transition to chronic pain, is expressed as prolongation of prostaglandin E2-induced hyperalgesia by the activation of an additional pathway including an autocrine mechanism at the plasma membrane. The autocrine mechanism involves the transport of cyclic adenosine monophosphate (AMP) to the extracellular space, and its conversion to AMP and adenosine, by ecto-5'phosphodiesterase and ecto-5'nucleotidase, respectively. The end product, adenosine, activates A1 receptors, producing delayed onset prolongation of prostaglandin E2 hyperalgesia. We tested the hypothesis that the previously reported, estrogen-dependent, sexual dimorphism observed in the induction of priming is present in the mechanisms involved in its expression, as a regulatory effect on ecto-5'nucleotidase by estrogen receptor α (EsRα), in female rats. In the primed paw AMP hyperalgesia was dependent on conversion to adenosine, being prevented by ecto-5'nucleotidase inhibitor α,β-methyleneadenosine 5'-diphosphate sodium salt and A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine. To investigate an interaction between EsRα and ecto-5'nucleotidase, we treated primed female rats with oligodeoxynucleotide antisense or mismatch against EsRα messenger RNA. Whereas in rats treated with antisense AMP-induced hyperalgesia was abolished, the A1 receptor agonist N -cyclopentiladenosine still produced hyperalgesia. Thus, EsRα interacts with this autocrine pathway at the level of ecto-5'nucleotidase. These results demonstrate a sexually dimorphic mechanism for the expression of priming. This study presents evidence of an estrogen-dependent mechanism of expression of chronic pain in female rats, supporting the suggestion that differential targets must be considered when establishing protocols for the treatment of painful conditions in men and women.

5'-Nucleotidase - metabolism

Adenosine - analogs & derivatives

Adenosine - toxicity

Adenosine A1 Receptor Antagonists - toxicity

Adenosine Monophosphate - toxicity

Animals

Chronic Pain - chemically induced

Chronic Pain - physiopathology

Dinoprostone - toxicity

Disease Models, Animal

DNA, Antisense - therapeutic use

Estrogen Receptor alpha - chemistry

Estrogen Receptor alpha - genetics

Estrogen Receptor alpha - metabolism

Female

Gene Expression Regulation - drug effects

Gene Expression Regulation - physiology

Hyperalgesia - drug therapy

Male

Pain Threshold - drug effects

Rats

Rats, Sprague-Dawley

Ryanodine - toxicity

Sex Factors

Time Factors

Xanthines - toxicity

Details

Title: Subtitle: Regulation of Expression of Hyperalgesic Priming by Estrogen Receptor α in the Rat
Creators: Luiz F Ferrari - University of California, San Francisco
Dionéia Araldi - University of California, San Francisco
Jon D Levine - University of California, San Francisco
Resource Type: Journal article
Publication Details: The journal of pain, Vol.18(5), pp.574-582
DOI: 10.1016/j.jpain.2016.12.017
PMID: 28089711
ISSN: 1526-5900
eISSN: 1528-8447
Grant note: R01 NS084545 / NINDS NIH HHS
Language: English
Date published: 05/01/2017
Academic Unit: Neuroscience and Pharmacology
Record Identifier: 9985177946702771

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