Therapeutic effects of p38 mitogen-activated protein kinase inhibition on hyperexcitability of capsaicin sensitive bladder afferent neurons in mice with spinal cord injury

Life Sci., 2023 · DOI: 10.1016/j.lfs.2023.121738 · Published: July 15, 2023

Simple Explanation

Spinal cord injury (SCI) can lead to bladder dysfunction due to changes in nerve excitability. This study investigates how a specific protein, p38 MAPK, affects bladder nerves in mice with SCI. The researchers examined the impact of inhibiting p38 MAPK on the electrical properties of bladder afferent neurons, which are sensitive to capsaicin (the active component of chili peppers). They found that inhibiting p38 MAPK reversed some of the changes in nerve excitability caused by SCI, suggesting this protein plays a role in bladder dysfunction after SCI.

Study Duration

4 Weeks

Participants

57 female C57BL/6 mice

Evidence Level

Not specified

Key Findings

1
SCI significantly reduced the spike threshold and increased the number of action potentials during 800 ms membrane depolarization in capsaicin-sensitive bladder afferent neurons.
2
The densities of slow-decaying A-type K+ (KA) and sustained delayed rectifier-type K+ (KDR) currents were significantly reduced by SCI.
3
The reduction of KA, but not KDR, current density was reversed by the treatment with p38 MAPK inhibitor.

Research Summary

This study investigated the role of p38 MAPK in the hyperexcitability of capsaicin-sensitive bladder afferent neurons in mice with spinal cord injury (SCI). The findings suggest that p38 MAPK plays an important role in the increased excitability of these neurons due to a reduction in KA channel activity after SCI. The study concludes that targeting NGF and its p38 MAPK downstream signaling pathway could be effective for treating lower urinary tract dysfunction, such as detrusor overactivity after SCI.

Practical Implications

Therapeutic Target

NGF and p38 MAPK downstream signaling pathway could be effective targets for the treatment of LUTD such as DO after SCI.

Drug Development

The findings suggest that drugs inhibiting p38 MAPK could potentially alleviate bladder dysfunction following spinal cord injury.

Understanding SCI

The study enhances the understanding of the mechanisms underlying bladder dysfunction after SCI, specifically highlighting the role of p38 MAPK.

Study Limitations

1
The study focused on changes in Kv channel activity after SCI, while p38 MAPK also modulates sodium channels.
2
The study did not include a group of SI mice treated with p38 MAPK inhibitors.
3
The results of our current study may not be applicable for the entire bladder afferent population.

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