Mas -related G-protein-coupled receptors inhibit pathological pain in mice

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• Nonpeptidergic and found on sensory neurons

in dorsal root ganglia

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

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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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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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

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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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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