Sex-/ovarian steroid-dependent release of endomorphin 2 from spinal cord.

Full Abstract

Mu-opioid receptor (MOR) agonists have been shown to be more potent analgesics in male than female rodents. Regulation of spinal MOR-coupled antinociception by 17beta-estradiol (estrogen, E2) and progesterone (P) is also sexually dimorphic; pregnancy levels of E2/P activate MOR-coupled analgesic pathways in male but not female rats. We hypothesized that the sexual dimorphic characteristics of MOR-coupled antinociception reflects sexual dimorphism in the regulation of the release from spinal cord of the endogenous MOR agonist, endomorphin 2 (EM2). Parameters of spinal EM2 release manifesting sexual dimorphism include its 1) magnitude:
in vitro basal and K+-evoked release of EM2 from spinal tissue of male rats is approximately 50% greater than that observed from spinal cord of females; 2) modulation by ovarian sex steroids:
E2/P treatment significantly enhanced K+-evoked EM2 release from spinal tissue of males, but not females; and 3) enhancement by opioid receptor blockade:
naloxone enhanced stimulated EM2 release from spinal tissue of both males and females, but it augmented basal release from spinal tissue of only males. Enhancement of EM2 release by naloxone reflects negative coupling of MOR to EM2 release and hence its modulation by negative feedback since only activation of MOR, not kappa-or delta-opioid receptors, was able to inhibit evoked EM2 release. These data reveal that the EM2-MOR spinal analgesic system is more robust and "higher gain" in male versus female rodents. These findings could provide a mechanistic rubric for understanding the male female dichotomy in prevalence and intensity of chronic pain syndromes.

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Author information

Author/s: Gupta, Daya S (DS); von Gizycki, Hans (H); Gintzler, Alan R (AR);

Affiliation: Box 8, Department of Biochemistry, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.

Grants: DA00289315 (Agency:NIDA NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther), published in United States. (Language: eng)

Reference: 2007-May; vol 321 (issue 2) : pp 635-41

Dates: Created 2007/04/17; Completed 2007/06/06; Revised 2007/12/03;

PMID: 17308039, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Dose-Response Relationship, Drug
Female
Gonadal Steroid Hormones - physiology
Male
Naloxone - pharmacology
Oligopeptides - secretion

Oligopeptides - secretion
Opioid Peptides - pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Opioid, mu - physiology
Sex Characteristics
Spinal Cord - secretion

Associated Chemicals: Gonadal Steroid Hormones (0) ; Oligopeptides (0) ; Opioid Peptides (0) ; Receptors, Opioid, mu (0) ; endomorphin 2 (0) ; nociceptin (0) ; Naloxone (465-65-6)

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