Estradiol acts in lateral thalamic region to attenuate varicella zoster virus associated affective pain
Autor: | Shaun M. Logan, Phillip R. Kramer, Mahesh Rao, Crystal Stinson, Paul R. Kinchington, Larry L. Bellinger |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty Herpesvirus 3 Human medicine.drug_class Glutamate decarboxylase Estrogen receptor Neuralgia Postherpetic Pain medicine.disease_cause Inhibitory postsynaptic potential Article 03 medical and health sciences Mice 0302 clinical medicine Internal medicine medicine Animals Phosphorylation Extracellular Signal-Regulated MAP Kinases Fulvestrant Estradiol Glutaminase business.industry General Neuroscience Varicella zoster virus Antagonist Estradiol binding 030104 developmental biology Endocrinology Estrogen Varicella Zoster Virus Infection Female business 030217 neurology & neurosurgery hormones hormone substitutes and hormone antagonists Lateral Thalamic Nuclei |
Popis: | Varicella zoster virus (VZV) results in chicken pox and herpes zoster. Female rats show a higher level of herpes zoster associated pain than males, consistent with human studies. In this study, we addressed the novel hypothesis that sex difference in herpes zoster associated pain is due, in part, to estradiol modulating activity in the thalamus. To test this hypothesis a high and low physiological dose of estradiol was administered to castrated and ovariectomized rats and the affective pain response was measured after injection of VZV into the whisker pad. Thalamic infusion of the estrogen receptor antagonist ICI 182,780 concomitant with a high dose of estradiol addressed the role of estradiol binding to its receptor to effect pain. Phosphorylated extracellular signal-regulated protein kinase (pERK) positive cells were measured in excitatory (glutaminase positive) and inhibitory (glutamate decarboxylase 67 positive) cells of the lateral thalamic region. Our results show that a high dose of estradiol significantly reduced the pain response in both males and females. pERK significantly increased in excitatory cells after treatment with a low dose of estradiol and increased in inhibitory cells after treatment with a high dose of estradiol. Administration of ICI 182,780 significantly increased the pain response, reduced expression of GABA related genes in the thalamic region and significantly reduced the number of inhibitory cells expressing pERK. The results suggest that estradiol attenuates herpes zoster pain by increasing the activity of inhibitory neurons within the thalamus and that this reduction includes an estrogen receptor dependent mechanism. |
Databáze: | OpenAIRE |
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