17-β-Estradiol induces spreading depression and pain behavior in alert female rats

Abstract

AimsTest the putative contribution of 17-β-estradiol in the development of spreading depression (SD) events and head pain in awake, non-restrained rats.Main MethodsFemale, Sprague-Dawley rats were intact or underwent ovariectomy followed one week later by surgery to place electrodes onto the dura to detect epidural electroencephalographic activity (dEEG). dEEG activity was recorded two days later for 12 hours after systemic administration of 17-β-estradiol (180 μg/kg, i.p.). A separate set of rats were observed for changes in exploratory, ambulatory, fine, and rearing behaviors; periorbital allodynia was also assessed.Key FindingsA bolus of 17-β-estradiol significantly elevated serum estrogen levels, increased SD episodes over a 12-hour recording period and decreased rearing behaviors in ovariectomized rats. Pre-administration of ICI 182,780, an estrogen receptor antagonist, blocked 17-β-estradiol-evoked SD events and pain behaviors; similar results were observed when the antimigraine therapeutic sumatriptan was used.SignificanceThese data indicate that an estrogen receptor-mediated mechanism contributes to SD events in ovariectomized rats and pain behaviors in both ovariectomized -and intact- rats. This suggests that estrogen plays a different role in each phenomenon of migraine where intense fluctuations in concentration may influence SD susceptibility. This is the first study to relate estrogen peaks to SD development and pain behaviors in awake, freely moving female rats, establishing a framework for future preclinical migraine studies.

Loss of Blood-Brain Barrier Integrity in a KCl-Induced Model of Episodic Headache Enhances CNS Drug Delivery

“…Non-evoked, or pain-suppressed behavior, was also assessed in response to CSD. Previous studies have shown that rearing behaviors are suppressed in response to facial allodynia ( Sandweiss et al, 2017 ; Zhang et al, 2017 ). The ability of cortical KCl to depress rearing behavior was assessed throughout the 72-h behavioral time course.…”

“…Notably, the time of BBB opening corresponded to the peak duration of periorbital allodynia as assessed behaviorally. Non-evoked measures of nociceptive behavior such as rearing have also been used to assess responses in preclinical models of headache ( Sandweiss et al, 2017 ; Zhang et al, 2017 ). Decreases in these non-evoked exploratory behaviors have been suggested to indicate a decrease in quality of life in these animals.…”

https://researchopenworld.com/migraine-a-review-of-basic-clinical-and-translational-approaches-to-new-treatment/#

“…The Dussor research group has developed several models for investigating sex-based differences in progesterone signaling leading to higher incidence of migraines observed in females. An animal model has been developed and utilized by this group to explore the relationship between elevated estrogen levels and specific response patterns to fluctuations of these female sex hormones, further relating to the translational application of progesterone as a treatment [27]. The Dussor and Russo labs have also investigated the differences of CGRP expression in a female model.…”

An underrepresented majority: A systematic review utilizing allodynic criteria to examine the present scarcity of discrete animal models for episodic migraine

“…In 2017, Sandweiss et al. published a protocol for inducing migraine-like pain in rodents, in which ovariectomized rats received a single ip bolus of high dose E2 (133). These rats demonstrated decreased exploratory behavior and decreased periorbital pain thresholds.…”