Sex-specificity and estrogen-dependence of kappa opioid receptor-mediated antinociception and antihyperalgesia

Autor: Analisa D. Thompson, S. S. Mokha, Subodh Nag, Kera P. Lawson
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Agonist
Male
Pain Threshold
medicine.medical_specialty
medicine.drug_class
Ovariectomy
Central nervous system
Estrogen receptor
Pain
Estrous Cycle
κ-opioid receptor
Naltrexone
Article
Rats
Sprague-Dawley
Internal medicine
Medicine
Animals
Testosterone
Orchiectomy
Injections
Spinal
Pain Measurement
Inflammation
Analysis of Variance
Sex Characteristics
Dose-Response Relationship
Drug
Estradiol
business.industry
Reverse Transcriptase Polymerase Chain Reaction
Receptors
Opioid
kappa
3
4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide
(trans)-Isomer
Lumbosacral Region
Analgesics
Non-Narcotic
Rats
Anesthesiology and Pain Medicine
Nociception
Endocrinology
medicine.anatomical_structure
Neurology
Spinal Cord
Estrogen
Area Under Curve
Female
Neurology (clinical)
Analgesia
business
hormones
hormone substitutes
and hormone antagonists
medicine.drug
Popis: This investigation determined whether the activation of the kappa opioid receptor (KOR) in the spinal cord produces estrogen-dependent, sex-specific modulation of acute and inflammation-induced persistent nociception. We demonstrate for the first time that KOR antinociception and gene expression are enhanced by exogenous or endogenous estrogen in the female. The lack of KOR antinociception and KOR gene expression are not altered by the hormonal status (testosterone or estrogen) in males. Cannulae were implanted intrathecally in male, gonadectomized male (GDX), intact and ovariectomized female (OVX) Sprague–Dawley rats. Estradiol was injected subcutaneously, 48 h before testing (GDX+E and OVX+E). Intrathecal injection of U50,488H, a selective KOR agonist, dose dependently increased heat-evoked tail flick latencies (TFLs) in proestrous and OVX+E groups, but not in male, GDX, GDX+E, OVX, and diestrous groups. Further, estrogen dose-dependently enhanced the effect of U50,488H in OVX rats. KOR selective antagonist, nor-binaltorphimine (Nor-BNI), blocked the antinociceptive effect of U50,488H. U50,488H reversed the carrageenan-induced thermal hyperalgesia in OVX+E rats, but not in male or OVX rats. However, U50,488H treatment did not alter mechanical thresholds in any group, with or without inflammation. KOR gene expression was enhanced in proestrous and OVX+E groups as compared to any other group. We conclude that selective activation of KOR in the spinal cord produces sex-specific, stimulus- and estrogen-dependent attenuation of acute and inflammatory pain in the rat via estrogen-induced upregulation of the KOR gene expression in the spinal cord. These findings may further implicate estrogen dependence of KOR effects in learning, epilepsy, stress response, addiction etc.
Databáze: OpenAIRE
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