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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

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

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  1. Mas-related G-protein-coupled receptors inhibit pathological pain in mice Travis Bjordahl

  2. 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

  3. 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

  4. 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

  5. Figure 1A

  6. Figure 1B

  7. 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

  8. Figure 2A

  9. Figure 2B

  10. Figure 2C

  11. Figure 2D

  12. Figure 2E

  13. 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

  14. 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

  15. Figure 3A

  16. Figure 3B

  17. Figure 3C

  18. Figure 3C

  19. Figure 3D

  20. Figure 3D

  21. 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

  22. Figure 4A

  23. Figure 4A

  24. Figure 4B

  25. Figure 4C

  26. Figure 4D

  27. Figure 4D

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