Microglial P2X4 receptors are essential for spinal neurons hyperexcitability and tactile allodynia in male and female neuropathic mice

iScience, 2023 · DOI: https://doi.org/10.1016/j.isci.2023.108110 · Published: November 17, 2023

Simple Explanation

This research investigates the role of P2X4 receptors in microglia, a type of immune cell in the spinal cord, in the development of neuropathic pain (nerve damage pain) in both male and female mice. The study finds that increased P2X4 on the surface of cells can cause increased sensitivity to touch and hyperexcitability of spinal cord neurons in both male and female mice. Blocking P2X4 receptors or a related molecule, TrkB, can relieve neuropathic pain, indicating that P2X4 in microglia is crucial for neuropathic pain regardless of sex.

Study Duration

Not specified

Participants

6-24 mice per condition, male and female, various genotypes (WT, P2X4KI, P2X4KO, myeloid P2X4KO)

Evidence Level

Not specified

Key Findings

1
Increased cell surface expression of P2X4 induces hypersensitivity to mechanical stimulations and hyperexcitability in spinal cord neurons of both male and female naive mice.
2
During neuropathy, both wild-type (WT) and P2X4KI mice of both sexes develop tactile allodynia accompanied by spinal neuron hyperexcitability.
3
The upregulation of P2X4 in microglia is crucial for neuropathic pain, regardless of sex.

Research Summary

The study demonstrates that increased cell surface expression of the P2X4 receptor induces hypersensitivity to mechanical stimulation and hyperexcitability in spinal cord neurons in both male and female mice. During neuropathy, both wild-type and P2X4KI mice of both sexes developed tactile allodynia and spinal neuron hyperexcitability, responses associated with P2X4. The upregulation of P2X4 in microglia is crucial for neuropathic pain, regardless of sex, and can be relieved by pharmacological blockade of P2X4 or TrkB.

Practical Implications

Therapeutic Target

P2X4 receptors in microglia represent a potential therapeutic target for the development of new pain medications.

Sex-Independent Treatment

The findings suggest that treatments targeting microglial P2X4 could be effective in both male and female patients with neuropathic pain.

Understanding Neuropathic Pain

The research contributes to a better understanding of the mechanisms underlying neuropathic pain and the role of neuroimmune interactions in its development.

Study Limitations

1
The study was conducted on mice, and the results may not be directly applicable to humans.
2
The specific mechanisms by which P2X4 in microglia leads to neuronal hyperexcitability and allodynia require further investigation.
3
The role of other immune cells and signaling pathways in neuropathic pain was not fully explored.

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