The Role of Brain Derived Neurotrophic Factor (BDNF) and Colony Stimulating Factor (CSF-1) In the Generation of Central Sensitization and Neuropathic Pain

• Author / Creator

  Boakye, Paul

• This dissertation addressed two main hypotheses:

  1. BDNF acts through different receptors and/or transduction mechanisms to increase release of excitatory transmitter onto excitatory neurons (using the Trk B signaling pathways) and to decrease release of excitatory transmitter onto inhibitory neurons (via the p75 signaling pathway).
  2. The release of CSF-1 by primary afferents after nerve injury leading to the generation of neuropathic pain involves an excitatory action on the dorsal horn mediated via the release of BDNF. Using an organotypic slice preparation of mice spinal cord slices, seven electrophysiological cell types were identified in the substantia gelatinosa of GAD67-EGFP Tamaguchi CL-1 white albino Swiss mice using whole-cell recording. Of the seven cell types, delay tonic and delay irregular, which are excitatory in nature almost never expressed GAD67 (GAD67-EGFP-) and are largely glutamatergic. Long term chronic studies using defined medium organotypic cultures (DMOTC) of mice spinal cords was established and it was determined that all the seven neuronal phenotypes found in acute slices were preserved in culture. The stability of the overall neuronal population decreased but stabilized over the entire duration in culture and slices were intact and healthy during the period of growth. These observations suggested the suitability of using defined medium organotypic cultures of mice spinal cord as long-term disease state models.

• Subjects / Keywords

  • Neuropathic Pain
  • Defined Medium Organotypic Cultures
  • Tamamaki mice
  • Brain Derived Neurotrophic Factor
  • Colony Stimulating Factor-1
  • substantia gelatinosa

• Graduation date

  Fall 2018

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3GT5FX58

• License

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