Transcript Travis Bjordahl

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
Figure 1A
Figure 1B
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
Figure 2A
Figure 2B
Figure 2C
Figure 2D
Figure 2E
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
Figure 3A
Figure 3B
Figure 3C
Figure 3C
Figure 3D
Figure 3D
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
Figure 4A
Figure 4A
Figure 4B
Figure 4C
Figure 4D
Figure 4D