Abstract
Brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) are known to contribute to both protective and pronociceptive processes. However, their contribution to neuropathic pain after spinal cord injury (SCI) needs further investigation. In a recent study utilizing TrkBF616A mice, it was shown that systemic pharmacogenetic inhibition of TrkB signaling with 1NM-PP1 (1NMP) immediately after SCI delayed the onset of pain hypersensitivity, implicating maladaptive TrkB signaling in pain after SCI. To examine potential neural mechanisms underlying the behavioral outcome, patch-clamp recording was performed in small-diameter dissociated thoracic (T) dorsal root ganglia (DRG) neurons to evaluate TrkB signaling in uninjured mice and after T10 contusion SCI. Bath-applied 7,8-dihydroxyflavone (7,8-DHF), a selective TrkB agonist, induced a robust inward current in neurons from uninjured mice, which was attenuated by 1NMP treatment. SCI also decreased 7,8-DHF-induced current while increasing the latency to its peak amplitude. Western blot revealed a concomitant decrease in TrkB expression in DRGs adjacent to the spinal lesion. Analyses of cellular and membrane properties showed that SCI increased neuronal excitability, evident by an increase in resting membrane potential and the number of spiking neurons. However, SCI did not increase spontaneous firing in DRG neurons. These results suggest that SCI induced changes in TrkB activation in DRG neurons even though these alterations are likely not contributing to pain hypersensitivity by nociceptor hyperexcitability. Overall, this reveals complex interactions involving TrkB signaling and provides an opportunity to investigate other, presumably peripheral, mechanisms by which TrkB contributes to pain hypersensitivity after SCI.