Persistent Link:
http://hdl.handle.net/10150/556881
Title:
Spinal Mechanisms of Hyperalgesic Priming
Author:
Kim, JiYoung
Issue Date:
2015
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The mechanisms that mediate the maintenance of chronic pain states are poorly understood, but elucidation of such could yield insight into how pain becomes chronic and how the process can potentially be reversed. This thesis investigated the role of ascending and descending spinal dorsal horn circuitry and interneurons in the plasticity that mediates a transition to pathological pain plasticity using hyperalgesic priming model. The results showed that, while dorsal horn neurokinin 1 receptor-positive neurons or descending serotonergic neurons mediated IL-6- and carrageenan-induced acute mechanical hypersensitivity, they were not required for PGE₂-induced mechanical hypersensitivity. In stark contrast, ablation of dopaminergic neurons did interrupt the IL-6- and carrageenan-induced mechanical hypersensitivity, but the subsequent PGE₂ injection failed to cause mechanical hypersensitivity - thereby reflecting that primed state plasticity is driven by differential mechanisms. In addition, the pharmacological antagonism of spinal dopamine D1/D5 receptors reversed priming and its agonism induced mechanical hypersensitivity exclusively in primed mice, which suggests dopaminergic control of pathological pain plasticity in a D1/D5-dependent manner. Moreover, in a primed state, changes to spinal dorsal horn GABA pharmacology were accompanied by upregulation of neuroligin 2 mRNA and protein expression. These findings 1) indicate a novel role for descending dopaminergic neurons in the maintenance of pathological pain plasticity, and 2) point to the inhibitory synaptic expression of neuroligin-2 as the spinal determinants of this type of pain plasticity.
Type:
text; Electronic Dissertation
Keywords:
Dopamine; GABA; Hyperalgesic Priming; NK1; Medical Pharmacology; Chronic Pain
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Medical Pharmacology
Degree Grantor:
University of Arizona
Advisor:
French, Edward; Price, Theodore J.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleSpinal Mechanisms of Hyperalgesic Primingen_US
dc.creatorKim, JiYoungen
dc.contributor.authorKim, JiYoungen
dc.date.issued2015en
dc.publisherThe University of Arizona.en
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en
dc.description.abstractThe mechanisms that mediate the maintenance of chronic pain states are poorly understood, but elucidation of such could yield insight into how pain becomes chronic and how the process can potentially be reversed. This thesis investigated the role of ascending and descending spinal dorsal horn circuitry and interneurons in the plasticity that mediates a transition to pathological pain plasticity using hyperalgesic priming model. The results showed that, while dorsal horn neurokinin 1 receptor-positive neurons or descending serotonergic neurons mediated IL-6- and carrageenan-induced acute mechanical hypersensitivity, they were not required for PGE₂-induced mechanical hypersensitivity. In stark contrast, ablation of dopaminergic neurons did interrupt the IL-6- and carrageenan-induced mechanical hypersensitivity, but the subsequent PGE₂ injection failed to cause mechanical hypersensitivity - thereby reflecting that primed state plasticity is driven by differential mechanisms. In addition, the pharmacological antagonism of spinal dopamine D1/D5 receptors reversed priming and its agonism induced mechanical hypersensitivity exclusively in primed mice, which suggests dopaminergic control of pathological pain plasticity in a D1/D5-dependent manner. Moreover, in a primed state, changes to spinal dorsal horn GABA pharmacology were accompanied by upregulation of neuroligin 2 mRNA and protein expression. These findings 1) indicate a novel role for descending dopaminergic neurons in the maintenance of pathological pain plasticity, and 2) point to the inhibitory synaptic expression of neuroligin-2 as the spinal determinants of this type of pain plasticity.en
dc.typetexten
dc.typeElectronic Dissertationen
dc.subjectDopamineen
dc.subjectGABAen
dc.subjectHyperalgesic Primingen
dc.subjectNK1en
dc.subjectMedical Pharmacologyen
dc.subjectChronic Painen
thesis.degree.namePh.D.en
thesis.degree.leveldoctoralen
thesis.degree.disciplineGraduate Collegeen
thesis.degree.disciplineMedical Pharmacologyen
thesis.degree.grantorUniversity of Arizonaen
dc.contributor.advisorFrench, Edwarden
dc.contributor.advisorPrice, Theodore J.en
dc.contributor.committeememberFrench, Edwarden
dc.contributor.committeememberPrice, Theodore J.en
dc.contributor.committeememberVanderah, Todden
dc.contributor.committeememberZinsmaier, Konraden
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