Price, Theodore J.
Permanent URI for this collectionhttps://hdl.handle.net/10735.1/4097
Theodore Price is an Associate Professor of Neuroscience. He is alos the head of the Pain Neurobiology Research Group. "Our laboratory is interested in the fundamental principles underlying pain plasticity. Our goal is to develop novel therapeutics based on these discoveries with the potential to either prevent the development of or permanently reverse chronic pain states. We focus on two major areas: 1) plasticity in peripheral nociceptive neurons following injury and, 2) plasticity in central nervous system circuits that results from persistent stimulation of peripheral nociceptors. We utilize molecular, biochemical, genetic, behavioral and electrophysiological techniques combined with an overarching interest in pharmacology and drug discovery to tackle this problem."
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Browsing Price, Theodore J. by Author "Avona, Amanda"
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Item Dural Calcitonin Gene-Related Peptide Produces Female-Specific Responses in Rodent Migraine Models(Society for Neuroscience, 2019-05-29) Avona, Amanda; Burgos-Vega, Carolina; Burton, Michael D.; Akopian, A. N.; Price, Theodore J.; Dussor, Gregory; 0000-0002-6971-6221 (Price, TJ); 0000-0002-0628-824X (Burton, MD); Avona, Amanda; Burgos-Vega, Carolina; Burton, Michael D.; Price, Theodore J.; Dussor, GregoryMigraine is the second leading cause for disability worldwide and the most common neurological disorder. It is also three times more common in women; reasons for this sex difference are not known. Using preclinical behavioral models of migraine, we show that application of calcitonin gene-related peptide (CGRP) to the rat dura mater produces cutaneous periorbital hypersensitivity. Surprisingly, this response was observed only in females; dural CGRP at doses from 1 pg to 3.8 μg produce no responses in males. In females, dural CGRP causes priming to a pH 7.0 solution after animals recover from the initial CGRP-induced allodynia. Dural application of interleukin-6 causes acute responses in males and females but only causes priming to subthreshold dural CGRP (0.1 pg) in females. Intracisternal application of BDNF also causes similar acute hypersensitivity responses in males and females but only priming to subthreshold dural CGRP (0.1 pg) in females. Females were additionally primed to a subthreshold dose of the NO-donor sodium nitroprusside (0.1 mg/kg) following dural CGRP. Finally, the sexually dimorphic responses to dural CGRP were not specific to rats as similar female-specific hypersensitivity responses were seen in mice, where increased grimace responses were also observed. These data are the first to demonstrate that CGRP-induced headache-like behavioral responses at doses up to 3.8 μg are female-specific both acutely and following central and peripheral priming. These data further implicate dural CGRP signaling in the pathophysiology of migraine and propose a model where dural CGRP-based mechanisms contribute to the sexual disparity of this female-biased disorder.SIGNIFICANCE STATEMENT Calcitonin gene-related peptide (CGRP) has long been implicated in the pathophysiology of migraine, and CGRP-based therapeutics are efficacious for the treatment of migraine in humans. However, the location of action for CGRP in migraine remains unclear. We show here that application of CGRP to the cranial meninges causes behavioral responses consistent with headache in preclinical rodent models. Surprisingly, however, these responses are only observed in females. Acute responses to meningeal CGRP are female-specific and sensitization to CGRP after two distinct stimuli are also female-specific. These data implicate the dura mater as a primary location of action for CGRP in migraine and suggest that female-specific mechanisms downstream of CGRP receptor activation contribute to the higher prevalence of migraine in women. Copyright © 2019 the authors.Item Non-Invasive Dural Stimulation in Mice: A Novel Preclinical Model of Migraine(Sage Publications Ltd, 2018-05-31) Burgos-Vega, Carolina Christina; Quigley, Lilyana D.; dos Santos, Gabriela Trevisan; Yan, Flora; Asiedu, Marina; Jacobs, Blaine; Motina, Marina; Safdar, Nida; Yousuf, Hayyan; Avona, Amanda; Price, Theodore J.; Dussor, Greg; Burgos-Vega, Carolina Christina; Quigley, Lilyana D.; Yan, Flora; Asiedu, Marina; Jacobs, Blaine; Motina, Marina; Safdar, Nida; Yousuf, Hayyan; Avona, Amanda; Price, Theodore J.; Dussor, GregBackground Migraine is characterized by a collection of neurological symptoms in the absence of injury or damage. However, several common preclinical migraine models require significant damage to the skull to stimulate the dura mater, the likely source of afferent signaling leading to head pain. The goal of this study was to determine whether dural stimulation can be performed in mice using an injection that does not cause injury or damage. Methods Using mice, injections of stimuli were administered to the dura mater through the soft tissue at the intersection between the lambdoidal and sagittal sutures. This technique did not require a permanent cannula nor did it cause damage to the skull or dura. Following injection of noxious stimuli, migraine-like behaviors were measured including cutaneous allodynia and facial grimace. The retrograde tracer fluorogold was applied onto the dura using the same injection technique to label trigeminal ganglion cell bodies, which were then testing in vitro using patch-clamp electrophysiology. Results Dural injection of allyl-isothiocyanate, low pH, interleukin-6, or inflammatory soup but not vehicles, led to cephalic/extracephalic allodynia. Facial grimace responses were also observed with allyl-isothiocyanate, pH 6.0, and interleukin-6. Stimulation with interleukin-6 causes priming to normally subthreshold pH 7.0 stimulation of the dura following resolution of the initial interleukin-6 behavior. Systemic injection of sumatriptan at the time of dural stimulation with inflammatory soup decreased the resulting cutaneous hypersensitivity. Trigeminal ganglion cell bodies retrogradely labeled from the dura had low pH-evoked currents similar to those generated by acid-sensing ion channels. Conclusion Non-invasive dural stimulation in mice can be used as a model of migraine in the absence of injury.