Humans and other animal species can experience many types of pain throughout the course of their lives, varying in intensity, unpleasantness, and origin. Several past neuroscience studies have explored the neural underpinnings of pain, yet the processes supporting the ability to distinguish different types of physical pain are not fully understood.
In most vertebrates, painful sensations are known to arise from the nervous system, which includes the brain, an intricate network of nerves and the spinal cord. While the brain’s contribution to the encoding and processing of pain has been widely explored in the past, the role that neural circuits in the spinal cord play in the differentiation of physical pain remains unclear.
Researchers at Karolinska Institute, Uppsala University and other institutes recently carried out a study aimed at better understanding how networks of nerve cells in the spinal cord of adult mice contribute to the encoding of pain originating from exposure to heat and mechanical pain, which is caused by applied physical forces (e.g., pinches, cuts, etc.).
Their findings, published in Nature Neuroscience, suggest that in mice, heat-related and mechanical pain are encoded by different neural ensembles (i.e., groups of neurons) in the spinal cord.
“How the spinal neural circuits attribute differences in quality of noxious information remains unknown,” wrote Ming-Dong Zhang, Jussi Kupari and their colleagues in their paper. “By means of genetic capturing, activity manipulation and single-cell RNA sequencing, we identified distinct neural ensembles in the adult mouse spinal cord encoding mechanical and heat pain.”
Zhang, Kupari and their colleagues performed a series of experiments on adult mice, employing various genetic techniques, including genetic capturing and single-cell RNA sequencing. These techniques allowed them to label specific neuron populations in the mouse spinal cord based on their activity while selectively activating or silencing these groups of neurons.
Interestingly, the researchers found that when they reactivated or silenced different neural ensembles, the animals behaved differently. When the neural ensembles were reactivated, the mice behaved in ways that suggested they were experiencing pain, for instance, shaking, lifting and licking their paws. When the neurons were silenced, they ceased these behaviors.
The results gathered by Zhang, Kupari and their collaborators also highlighted the crucial role of Gal+ inhibitory neurons in the discrimination of pain. These are a class of neurons that contribute to the suppression of pain-related signals via the production of the neuropeptide galanin (Gal).
“Within ensembles, polymodal Gal+ inhibitory neurons with monosynaptic contacts to A-fiber sensory neurons gated pain transmission independent of modality,” wrote Zhang, Kupari and their colleagues.
“Peripheral nerve injury led to inferred microglia-driven inflammation and an ensemble transition with decreased recruitment of Gal+ inhibitory neurons and increased excitatory drive. Forced activation of Gal+ neurons reversed hypersensitivity associated with neuropathy.”
This recent study offers new, valuable insight into the contribution of neural ensembles in the spinal cord of mice to the animals’ encoding of pain of a heat-related and mechanical origin. If they are found to also apply to humans, these findings could eventually contribute to the development of new medications and therapeutic interventions for pain relief. In addition, they could inspire further research examining the role of the spinal cord in the differentiation of pain.
“Our results reveal the existence of a spinal representation that forms the neural basis of the discriminative and defensive qualities of acute pain, and these neurons are under the control of a shared feed-forward inhibition,” wrote Zhang, Kupari and their colleagues.
https://medicalxpress.com/news/2025-04-neuron-groups-mice-spinal-cord.html
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