The role of spinal Chrna3-expressing neurons in the pain transmission

The spinal dorsal horn is the primary integration center for somatosensory information. However, the specific neuronal populations responsible for encoding distinct modalities, including pain, remain poorly defined. Here, we performed a deep functional and neurochemical characterisation of a genetically-defined neuronal population in the superficial dorsal horn that expresses the nicotinic acetylcholine receptor subunit Chrna3 (Chrna3+), using Chrna3-eGFP transgenic mice. Our data suggest that spinal Chrna3+ neurons are selectively tuned to acute noxious inputs from Aδ and C-fiber afferents. Remarkably, this population showed profound functional stability. Neither peripheral inflammation nor pharmacological disinhibition significantly altered their synaptic input profile, failing to unmask Aβ-fiber inputs or their intrinsic excitability. This stands in stark contrast to neighbouring Chrna3- neurons, which showed robust plasticity. Our findings define the Chrna3+ population as a highly specialized and functionally insulated circuit. Instead of participating in plastic changes associated with chronic pain states, these neurons appear to function as a robust „binary switch“ for relaying acute nociceptive information from Aδ and C-fibers. This functional stability identifies the Chrna3+ neurons as a potential target for modulating acute pain, distinct from the mechanisms of pain chronification.

Biography: Dr. Pavel Adámek is a neuroscientist who has recently joined the Laboratory of Pain Research at BIOCEV, supported by a Marie Skłodowska-Curie COFUND MERIT fellowship. He returns to Prague following his postdoc at the University Medical Center Hamburg-Eppendorf (UKE) in laboratory of Prof. Stefan G. Lechner. His research focuses on the cellular mechanisms of pain. His previous work, conducted during his Ph.D. in the lab of Dr. Jiří Paleček, identified key mechanisms underlying chemotherapy-induced neuropathic pain. Later on, during his post-doc in Hamburg, he focused on the functional organization of spinal cord circuits involved in nociceptive processing. In his talk, Dr. Adámek will present the primary findings from his postdoctoral project: a multidisciplinary characterization of the Chrna3+ neuronal population in the dorsal horn. Combining quantitative immunohistochemistry, neuronal reconstruction and ex vivo electrophysiology, the study reveals that spinal Chrna3+ neurons serve as a highly specialized circuit for acute nociceptive signaling.

IPHYS contact person: Jiří Paleček, Laboratory of Pain Research, jiri.palecek@fgu.cas.cz

Funding: The programme is co-funded by the European Union’s Horizon Europe programme under the Marie Skłodowska-Curie Actions COFUND scheme and by the Central Bohemian Region.