Tmem45b is essential for inﬂammation- and tissue injury–induced mechanical pain hypersensitivity

PNAS, 2022 · DOI: https://doi.org/10.1073/pnas.2121989119 · Published: November 2, 2022

Simple Explanation

Persistent pain hypersensitivity interferes with daily activities and quality of life. The underlying molecular mechanisms are not completely understood. This study identifies Tmem45b as a key molecule in inflammation- and tissue injury-induced mechanical pain hypersensitivity. IB4+ sensory neurons are selectively involved in inflammation- and tissue injury–induced mechanical pain hypersensitivity. Tmem45b is predominantly expressed in these IB4+ DRG neurons. Mice lacking Tmem45b show normal responses to noxious stimuli but do not exhibit mechanical pain hypersensitivity in inflammation and tissue injury. This suggests Tmem45b as a potential therapeutic target.

Study Duration

Not specified

Participants

Adult male and female C57BL/6N mice and Tmem45b-KO C57BL/6N mice

Evidence Level

Not specified

Key Findings

1
IB4+ sensory neurons are selectively involved in inflammation- and tissue injury–induced mechanical pain hypersensitivity, but not in neuropathic pain.
2
Tmem45b is predominantly expressed in IB4+ DRG neurons and is essential for inflammation- and tissue injury–induced mechanical pain hypersensitivity.
3
Acute knockdown of Tmem45b reduces mechanical pain hypersensitivity, suggesting it as a potential therapeutic target.

Research Summary

This study identifies Tmem45b as a crucial molecule for inflammation- and tissue injury-induced mechanical pain hypersensitivity. Tmem45b is mainly expressed in IB4+ sensory neurons. Tmem45b-knockout mice exhibited a selective loss of mechanical pain hypersensitivity in inflammatory and tissue injury pain models, but not in neuropathic pain models. Acute knockdown of Tmem45b using siRNA reduced mechanical pain hypersensitivity, supporting its potential as a therapeutic target for chronic pain.

Practical Implications

Therapeutic Target

Tmem45b presents a novel therapeutic target for treating mechanical pain hypersensitivity associated with inflammation and tissue injury.

Pain Mechanism

The study provides insights into the molecular mechanisms underlying specific types of mechanical pain, particularly those involving IB4+ sensory neurons and Tmem45b.

Drug Development

These findings may contribute to the development of targeted therapies that reduce pathological pain without affecting normal pain sensation or causing central nervous system side effects.

Study Limitations

1
The study focuses on mice, and the findings may not be directly translatable to humans.
2
The precise function of Tmem45b in the trans Golgi apparatus of DRG neurons remains unknown.
3
The study does not fully elucidate the downstream signaling pathways through which Tmem45b mediates mechanical pain hypersensitivity.

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