Robert P. Ganley, Marília Sousa, Kira Werder, and their team unveil targeted identification of serotonergic neurons influencing pain perception in their recent publication in eLife.
Ganley, Sousa, Werder, and colleagues highlight two separate populations of serotonergic neurons in the hindbrain that influence pain sensitivity differently. Using virus-based strategies and Tph2-Cre transgenic mice, they identified neurons located in the lateral paragigantocellularis (LPGi) and the medial hindbrain. These neurons respectively innervate the superficial and deep spinal dorsal horn, and their activation yields contrasting effects on sensory perception.
The team found LPGi neurons more susceptible to transduction with spinally injected AAV2retro vectors than their medial hindbrain counterparts. Leveraging this difference, they showed that activating LPGi serotonergic projections reduces thermal sensitivity, while activating medial serotonergic neurons increases sensitivity to mechanical stimulation.
These findings suggest distinct serotonergic hindbrain neurons vary in anatomical location, postsynaptic targets in the spinal cord, and impact on nociceptive sensitivity. LPGi neurons with global and bilateral projections could contribute to widespread systemic pain control.