TrkB Agonist (7,8-DHF)-Induced Responses in Dorsal Root Ganglia Neurons Are Decreased after Spinal Cord Injury: Implication for Peripheral Pain Mechanisms

eNeuro, 2025 · DOI: https://doi.org/10.1523/ENEURO.0219-24.2024 · Published: January 1, 2025

Spinal Cord Injury Neurology Pain Management

Simple Explanation

This study examines how TrkB signaling, which involves a protein called TrkB, changes in nerve cells near the spinal cord after a spinal cord injury (SCI). These changes could be related to the pain that develops after such injuries. The study found that after a spinal cord injury, the response of these nerve cells to a drug that activates TrkB is reduced. Additionally, the amount of TrkB protein in these cells also decreases. These results suggest that although TrkB signaling in DRG neurons might not underlie nociceptor hyperexcitability or neuropathic pain, more specific targeting of TrkB mechanisms, includ- ing peripheral components, is needed to address SCI-induced pain.

Study Duration

3-4 Weeks

Participants

55 adult male and female Ntrk2F616A (F616) mice

Evidence Level

Not specified

Key Findings

1
SCI decreased 7,8-DHF-induced current while increasing the latency to its peak amplitude.
2
SCI induced changes in TrkB activation in DRG neurons even though these alterations are likely not contributing to pain hypersensitivity by nociceptor hyperexcitability.
3
SCI led to a less negative resting membrane potential and more neurons fired an action potential once the threshold was reached.

Research Summary

The study investigated TrkB signaling in DRG neurons as a potential neural mechanism that underlies pain hypersensitivity after SCI. The results revealed that TrkB-mediated inward current and its protein expression are drastically reduced in the DRG after SCI. SCI altered several neuronal properties, consistent with increased neuronal hyperexcitability, although not exclusively in a TrkB-dependent manner.

Practical Implications

Peripheral Mechanisms

The locus of TrkB-mediated pain hypersensitivity may be more peripheral than the DRGs.

Complex TrkB Changes

Complex results reveal a potential multifaceted nature of the changes in TrkB expression. Further research is needed to determine the exact changes to TrkB cell surface expression.

Potential Multifaceted Nature

Further studies are needed to fully elucidate the role of TrkB signaling in pain hypersensitivity after SCI through specific targeting of TrkB

Study Limitations

1
The small-diameter neurons in the electrophysiological recordings are not ascertained to be nociceptors.
2
An important concern is whether the expression of the mutated TrkB in F616 mice fully recapitulates that of native TrkB.
3
Sensory neurons are sensitive to the dissociation process, enzymatic and mechanical dissociation and the 24 h incubation period may have allowed an altered phenotype to be established in neurons, thereby changing their properties.

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