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Shan-Jing Geng, et al. 2010

Contribution of the spinal cord BDNF to the development of neuropathic pain by activation of the NR 2B -containing NMDA receptors in rats with spinal nerve ligation. Shan-Jing Geng, et al. 2010. “brain food”. -~ BDNF ~-. BDNF added. Control. Receptor for BDNF Involved in synaptogenesis

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Shan-Jing Geng, et al. 2010

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  1. Contribution of the spinal cord BDNF to the development of neuropathic pain by activation of the NR2B-containing NMDA receptors in rats with spinal nerve ligation Shan-Jing Geng, et al. 2010

  2. “brain food” -~BDNF~- BDNF added Control

  3. Receptor for BDNF • Involved in synaptogenesis • More receptors, more response - TrkB -

  4. NMDA • Calcium channel involved in plasticity Ca2+ Glutamate

  5. NMDA • Channels made out of 4 subunits • NR2 has different isoforms: NR2 A, B, C, D Today we care about NR2B Ca2+ NR1 NR2 Glutamate

  6. NMDA • NR2B • In the context of neuropathic pain it Potentiates the signal CAUSING pain • Can’t have neuropathic pain w/o NR2B • (It’s wicked important)

  7. The mechanism BDNF NMDA channel TrkB receptor NR2B NR2B

  8. “Chain of Pain” Brain • Pain receptor • Mechanical • polymodal Spinothalamic tract Dorsal Horn: Lamina I & II C & A δ Fibers

  9. “Chain of Pain” Light Brain Spinothalamic Tract Dorsal Horn C & Aδ Fibers Pain Receptor

  10. Dorsal Horn was examined • Immunohistochemistryfor BDNF & NR2B • Lamina I & II • ElisaKitfor BDNF • Dorsal horn • Western for TrkB • Dorsal horn

  11. Spinal Nerve Ligation (SNL) Poor Rats  • Induces neuropathic pain Intrathecal Catheter Implant Makes for a precise injection

  12. ?

  13. Von Frey Filiments

  14. R2=0.94 Early Late R2=0.11

  15. BDNF NMDA channel TrkB receptor NR2B NR2B

  16. BDNFimmunohistochemical

  17. Follows the pattern of BDNF TrkB

  18. NR2Bimmunohistochemical

  19. BDNF NR2B

  20. NR2B Blocker (antagonist) • Co-administered with BDNF • Does not affect BDNF binding or signaling Ro 25-6981 experiment

  21. Ro BDNF TrkB receptor NR2B NR2B

  22. NR2B is essential to BDNF mediated neuropathic pain • BDNF initiates Neuropathic pain • NR2B keeps it going • Why does pain stay when NR2B goes back down? • AMPA Almost there..

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