mas -related g-protein-coupled receptors inhibit pathological pain in mice
DESCRIPTION
Mas -related G-protein-coupled receptors inhibit pathological pain in mice. Travis Bjordahl. Mrgprs. Mrgprs are orphan receptors related to MAS1 MAS1 binds angiotensin 1-7 and opposes angiotensin-2 type 1 receptors All have 7 transmembrane helices Are believed to be immediate early genes - PowerPoint PPT PresentationTRANSCRIPT
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Mas-related G-protein-coupled receptors inhibit pathological pain in
mice
Travis Bjordahl
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Mrgprs
• Mrgprs are orphan receptors related to MAS1• MAS1 binds angiotensin 1-7 and opposes
angiotensin-2 type 1 receptors• All have 7 transmembrane helices • Are believed to be immediate early genes• Nonpeptidergic and found on sensory neurons
in dorsal root ganglia
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Experimental Overview
• 12 Mrgpr sequences deleted in KO mice• Studied sensitization between KO and WT
mice• Effect of Mrgpr agonists on persistant
inflammatory and neuropathic pain• Effect of agonists on neuron sensitization
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Do Mrgprs Modulate Pain?
• Injected formalin solution(2% ; 5µL) into plantar tissue of one hind paw
• Observed first phase nociceptor activation and second phase tissue inflammation
• Studied expression of c-fos in neurons in laminae I and II of L4-L6
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Figure 1A
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Figure 1B
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Do Mrgprs Effect Sensitization of Wide Dynamic Range Neurons
• Repeated stimuli sensitize neurons and increase excitability
• Studied sensitization of neurons in KO and WT mice
• KO mice showed increased sensitization and excitability compared to WT
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Figure 2A
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Figure 2B
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Figure 2C
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Figure 2D
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Figure 2E
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Effect of Mrgpr Agonists on Pain
• Used bovine adrenal medulla peptide 8-22 as agonist
• Looked at how BAM 8-22 changed responses to thermal stimuli in mice with persistent inflammatory pain
• Studied effect of BAM 8-22 on mechanical allodynia after nerve ligation
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Thermal Hyperalgesia
• Injected CFA into hind paw• Intrathecally injected BAM 8-22 to treat pain• Observed difference between effect on acute
and chronic thermal pain using Hargreaves test
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Figure 3A
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Figure 3B
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Figure 3C
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Figure 3C
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Figure 3D
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Figure 3D
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Mrgpr Agonist BAM 8-22 Inhibits Sensitization
• Used electrical stimulation to cause sensitization of WDR neurons
• Addition of BAM 8-22 reduced sensitization in WT mice
• BAM 8-22 increased windup and excitability of WDR neurons in KO mice
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Figure 4A
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Figure 4A
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Figure 4B
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Figure 4C
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Figure 4D
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Figure 4D