A study highlights the mechanism responsible for differential processing of these pain signals in the spinal cord.
Story by Jean Hamann, translation by CERVO
Why is it that the pain of a burn seems more intense and lasts longer than the pain of a pinch? “Intuitively, I thought it was because the burn caused more physical damage to the skin,” says Professor Yves De Koninck of the Faculty of Medicine and the CERVO Brain Research Centre. Our recent work, however, suggests another explanation for this phenomenon and this lead is helping us to better understand how the nervous system processes pain signals”.
In an article published in Nature Communications, two members of Professor De Koninck’s team, Francesco Ferrini and Jimena Perez-Sanchez, explain how they used optogenetic procedures to stimulate, using a light beam, thermal and mechanical receptors located in the paws of genetically modified mice. “These stimulations do not cause any physical damage, but they trigger the same sensory responses as a burn or a pinch,” explains Professor De Koninck.
Like several other pain studies previously carried out by this team, the test findings suggest that the KCC2 protein plays a central role in the differential processing of pain signals. “This transporter, which regulates the concentration of chloride ions within the neurons of the spinal cord, is a key element of the gate system that determines whether or not a pain signal from sensory nerves is relayed to the brain,” De Koninck recalls. Its role is to inhibit the transmission of the pain signal. When this protein is less abundant, the pain signals are relayed more to the brain”.
The researchers found that the different layers of the spinal cord are not equally provided with KCC2. “This protein is half as abundant in the top layer as in the layer immediately below,” says Professor De Koninck. However, the nerve fibres that transmit thermal pain signals mainly end up in the first layer, while those that transmit mechanical pain mainly end up in the second layer. This suggests that thermal pain signals are transmitted more to the brain because there is less KCC2 to inhibit them. The system then tends to overload itself, which causes increased and prolonged sensitivity”.
This mechanism could have an adaptive value for living beings, the researcher suggests. “The damage caused by a burn is generally more severe than that produced by a pinch. To ensure its protection, the organism therefore has every interest in being particularly sensitive to thermal signals. For example, in humans, the burning sensation is felt as soon as the water reaches a temperature of 45 degrees Celsius, even if this is not enough to cause physical damage”.
For the moment, the conclusions of this study are mainly of fundamental interest. “On the other hand, they could help us better understand the mechanisms involved in neuropathic pain that manifests itself after a trauma or illness and that poison the lives of those who suffer from it. We will soon publish a study on this issue,” says Professor De Koninck.
The other authors of the study are Samuel Ferland, Louis-Étienne Lorenzo, Antoine Godin, Isabel Plasencia-Fernandez, Martin Cottet, Annie Castonguay, Feng Wang and Nicolas Doyon, from Université Laval, and their colleagues from the University of Turin, Chiara Salio and Adalberto Merighi.
Read the original story, in French on the nouvelles.ulaval.ca website
Read the original scientific article in Nature Communications:
Ferrini, F., Perez-Sanchez, J., Ferland, S., Lorenzo, L. E., Godin, A. G., Plasencia-Fernandez, I., Cottet, M., Castonguay, A., Wang, F., Salio, C., Doyon, N., Merighi, A., & De Koninck, Y. (2020). Differential chloride homeostasis in the spinal dorsal horn locally shapes synaptic metaplasticity and modality-specific sensitization. Nature communications, 11(1), 3935. https://doi.org/10.1038/s41467-020-17824-y
