Elevated serotonin in mouse spinal dorsal horn is pronociceptive

bioRxiv preprint, 2023 · DOI: https://doi.org/10.1101/2023.08.10.552838 · Published: August 14, 2023

Simple Explanation

The study investigates how serotonin, a chemical in the brain, affects pain processing in mice. Specifically, it looks at the role of serotonin released in the spinal cord from a brain region called the rostral ventral medulla (RVM). The researchers found that activating serotonin-releasing neurons in the spinal cord made the mice more sensitive to pain and caused them to avoid places where these neurons were activated. This suggests that serotonin can increase pain. In mice with a nerve injury that causes chronic pain, the researchers found higher levels of serotonin in a specific area of the spinal cord. This suggests that increased serotonin levels may contribute to chronic pain.

Study Duration

Not specified

Participants

Adult male and female transgenic mice

Evidence Level

Not specified

Key Findings

1
Optogenetic activation of RVM serotonergic afferents in the spinal cord produces mechanical hypersensitivity and conditioned place aversion in naïve mice.
2
Neuropathic pain evoked a tonic increase in serotonin concentrations within the spinal trigeminal nucleus caudalis (SpVc).
3
CCI-ION had no effect on the phasic serotonin transients in SpVc, evoked by noxious pinch.

Research Summary

This study investigates the contribution of RVM serotonergic neurons to pain processing in the spinal trigeminal nucleus caudalis (SpVc) in acute and chronic pain models in mice. The findings suggest that serotonin release in the spinal cord is pronociceptive, and that a sustained increase in serotonin levels, rather than event-driven release, contributes to chronic pain phenotypes. Optogenetic activation of RVM5HT terminals in SpVc produces mechanical allodynia and aversion, while tonic serotonin levels are elevated in SpVc of mice with trigeminal neuropathy.

Practical Implications

Therapeutic Target

Targeting spinally projecting RVM5HT neurons may be a viable therapeutic approach in treating chronic pain.

Understanding Serotonin's Role

Further clarifying the role of serotonin in nociception can aid in developing more effective and targeted pain management strategies.

Local Inhibition

Local inhibition of serotonin release or increased uptake may be a viable therapeutic approach in treating chronic pain.

Study Limitations

1
The exact mechanisms through which RVM5HT neurons begin to facilitate nociception are unknown.
2
The study did not directly test whether sex contributes to the effect size due to an insufficient number of each sex.
3
Changes in expression patterns of serotonin receptor subtypes complicate understanding the impact of sustained increases in serotonergic signaling on nociception.

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