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Contribution of Spinal Cord BDNF to Neuropathic Pain: NR2B Activation in Rats

This study explores the role of spinal cord BDNF in neuropathic pain development by activating NR2B-containing NMDA receptors in rats with spinal nerve ligation. The research delves into the interplay of BDNF, NR2B, TrkB receptors, and NMDA channels in the context of pain signal potentiation. Immunohistochemistry and ElisaKit techniques were employed to examine BDNF and NR2B expression in the dorsal horn. Results show the essential role of NR2B in mediating neuropathic pain, with implications for pain management strategies. The findings shed light on the intricate "Chain of Pain" mechanism involving BDNF, TrkB receptors, NR2B, and NMDA channels in the spinal cord.

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Contribution of Spinal Cord BDNF to Neuropathic Pain: NR2B Activation in Rats

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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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