Pharmacogenetic inhibition of TrkB signaling in adult mice attenuates mechanical hypersensitivity and improves locomotor function after spinal cord injury

Frontiers in Cellular Neuroscience, 2022 · DOI: 10.3389/fncel.2022.987236 · Published: September 26, 2022

Spinal Cord Injury Neurology Pain Management

Simple Explanation

This study explores how a specific signaling pathway (BDNF-TrkB) contributes to pain and impaired movement after spinal cord injury (SCI) in mice. BDNF, a brain-derived neurotrophic factor, signals through the TrkB receptor. The researchers used a special type of mouse (TrkBF616) that allows them to temporarily block TrkB signaling using a drug called 1NM-PP1 (1NMP). They then observed the effects on pain sensitivity, movement, and changes in the spinal cord and skin. The findings suggest that blocking TrkB signaling shortly after SCI can reduce pain and improve motor function. This indicates that early TrkB signaling contributes to the development of maladaptive changes leading to pain and impaired movement.

Study Duration

4 weeks

Participants

TrkBF616 and wild-type C57BL/6 mice

Evidence Level

Original Research

Key Findings

1
Inhibition of TrkB signaling after SCI attenuates the onset and maintenance of mechanical hypersensitivity after SCI.
2
Early inhibition of TrkB signaling immediately after SCI improves the recovery of locomotion.
3
At the cellular level, 1NMP treatment prevented the increases in spinal pERK1/2 expression otherwise seen after SCI.

Research Summary

The study investigates the role of TrkB signaling in pain and locomotor dysfunction following spinal cord injury (SCI) in mice using pharmacogenetic inhibition. Results indicate that early TrkB inhibition after SCI attenuates mechanical hypersensitivity, improves locomotor recovery, and prevents SCI-induced increases in spinal pERK1/2 expression. The findings suggest that early onset TrkB signaling after SCI contributes to maladaptive plasticity, leading to pain hypersensitivity and impaired locomotor function.

Practical Implications

Therapeutic Potential

Early intervention targeting TrkB signaling could produce beneficial outcomes after SCI.

Maladaptive Plasticity

Early onset TrkB signaling has the potential to produce maladaptive plasticity, leading to pain hypersensitivity and compromised locomotor recovery.

Further Investigation

Further investigation into the role of BDNF-TrkB signaling in chronic neuropathic pain after SCI is needed.

Study Limitations

1
The exact site of action (central vs. peripheral) of 1NMP is unknown.
2
Whether early blockade of TrkB signaling remains effective in the more chronic stages of injury is unknown.
3
Potential widespread actions of small molecule kinase inhibitors need consideration regarding the speciﬁcity of 1NMP treatment.

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