Targeted up-regulation of Drp1 in dorsal horn attenuates neuropathic pain hypersensitivity by increasing mitochondrial fission

Redox Biology, 2022 · DOI: https://doi.org/10.1016/j.redox.2021.102216 · Published: January 1, 2022

Simple Explanation

This study explores the role of Drp1, a protein involved in mitochondrial fission, in neuropathic pain (NP). They used a spared nerve injury (SNI) model in mice to mimic NP. The study found that SNI increased Drp1 levels and altered mitochondrial structure in the spinal dorsal horn (SDH), a key area for pain processing. By manipulating Drp1 levels in the SDH, the researchers observed changes in pain sensitivity and anxiety-like behaviors in the SNI mice. Overexpressing Drp1 seemed to alleviate pain, while down-regulating Drp1 did not have the same beneficial effects. The study also examined mitochondrial structure in detail, finding that Drp1 overexpression helped restore normal mitochondrial structure after SNI. These findings suggest that Drp1 and mitochondrial fission may be potential therapeutic targets for neuropathic pain.

Study Duration

Not specified

Participants

Adult male C57BL/6 J mice

Evidence Level

Not specified

Key Findings

1
SNI in mice induces pain behavior and anxiety-like behavior, which is associated with elevation of Drp1, as well as increased density of mitochondria in SDH.
2
Targeted up-regulation of Drp1 within SDH alleviated pain symptoms in SNI mice, while targeted down-regulation of Drp1 did not have the analgesic effect.
3
Up-regulation of Drp1 reduced mitochondrial number, but did not change the external and internal appearance of the mitochondria induced by SNI; on the contrary, down-regulation of Drp1 led SDH mitochondria to be more swollen and with more broken cristae.

Research Summary

This study investigates the role of Dynamin-related protein 1 (Drp1), a key regulator of mitochondrial fission, in neuropathic pain (NP) using a spared nerve injury (SNI) model in mice. The research focuses on the spinal dorsal horn (SDH), a critical area for pain signal processing. The researchers found that SNI leads to pain and anxiety-like behaviors, increased Drp1 levels, and changes in mitochondrial structure within the SDH. These changes include increased mitochondrial density and altered morphology. Manipulating Drp1 levels via overexpression and RNA interference revealed that targeted up-regulation of Drp1 in the SDH alleviates pain symptoms, while down-regulation exacerbates mitochondrial damage and does not provide pain relief, suggesting Drp1 as a potential therapeutic target.

Practical Implications

Therapeutic target

Drp1 could be a novel therapeutic target for pain treatment.

Mitochondrial health

Maintaining mitochondrial health and dynamics could be crucial in managing neuropathic pain.

Further research

Further research is needed to fully understand the mechanisms by which Drp1 affects pain processing and mitochondrial function.

Study Limitations

1
Drp1 OE could not significantly up-regulate Drp1 mRNAs detected by qRT-PCR method, although Drp1 OE could significantly up-regulate Drp1 proteins detected by Western Blot.
2
Our present observation did not distinguish the neuronal types. So in the future, it is necessary to use GABA associated transgenic mice to make research on mitochondrial plasticity.
3
Although many studies have deduced the mitochondrial dysfunction underlying NP, mainly based on the alternation of regulator factors involved in mitochondrial fission or fusion, such as Drp1, Mfn1, or Opa1, studying of mitochondria morphology in nervous system tissue is very limited.

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