The clinically-approved compounds, pramipexole and dexpramipexole, reverse chronic allodynia from sciatic nerve damage in mice, and alter IL-1β and IL-10 expression from immune cell culture

Neurosci Lett, 2023 · DOI: 10.1016/j.neulet.2023.137419 · Published: September 25, 2023

Simple Explanation

Neuropathic pain often involves hypersensitized nerve cells releasing signals in the spinal cord. This leads to activation of glial cells, which then release pro-inflammatory cytokines, enhancing pain transmission. This process ultimately results in light touch hypersensitivity, known as allodynia. Pramipexole, typically used for Parkinson's disease, has shown promise in reducing inflammatory pain in animal models. Dexpramipexole, a related compound with fewer dopamine-related side effects, has also demonstrated efficacy in both inflammatory and neuropathic pain models. This study uses a mouse model of sciatic nerve neuropathy to investigate whether pramipexole and dexpramipexole can reverse chronic allodynia and affect the production of inflammatory and anti-inflammatory substances in immune cells.

Study Duration

Not specified

Participants

Adult male and female C57BL/6 mice, Long-Evans rats

Evidence Level

Not specified

Key Findings

1
Both pramipexole and dexpramipexole significantly reduced allodynia in mice within one hour of intravenous injection, although the effect was temporary, with allodynia returning after 24 hours.
2
Pramipexole was found to significantly decrease the production of IL-1β protein from stimulated human monocytes, suggesting a direct anti-inflammatory effect.
3
Dexpramipexole induced an increase in the expression of IL-10 mRNA from rat splenocytes, indicating that it promotes the production of an anti-inflammatory cytokine.

Research Summary

This study investigates the effects of pramipexole and dexpramipexole on chronic allodynia and cytokine expression in mice with sciatic nerve damage. The researchers hypothesized that both compounds would reverse chronic neuropathy and alter cytokine production in immune cell cultures. The results show that both pramipexole and dexpramipexole effectively reduce allodynia in mice, but only temporarily. Furthermore, pramipexole reduces IL-1β production in human monocytes, and dexpramipexole increases IL-10 mRNA expression in rat splenocytes. The authors conclude that these clinically-approved compounds have potential as anti-inflammatory agents to treat chronic neuropathy, offering a basis for developing new, opioid-independent treatments for neuropathic pain.

Practical Implications

Potential for New Pain Treatments

Pramipexole and dexpramipexole could offer new, non-opioid options for managing chronic neuropathic pain.

Targeting Inflammation

The drugs' anti-inflammatory properties suggest that targeting inflammation may be a viable strategy for treating neuropathic pain.

Multifaceted Approaches

Future pain treatments could benefit from a multifaceted approach that targets multiple mechanisms, such as inflammation and nerve signaling.

Study Limitations

1
The anti-allodynic effects of both drugs are transient.
2
The study does not fully explain the mechanisms through which pramipexole reduces NF-kB activation and IL-1β production.
3
The study acknowledges that the dexpramipexole may induce IL-10 production without splenocyte stimulation.

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