The world has changed since 1664, when the French philosopher and scientist René Descartes first claimed that the brain was responsible for feeling the sensation of pain.
However, one key question remains: how exactly does the human brain feel pain? Specifically, thermal pain, such as that experienced when you touch an open flame or a hot pan while cooking.
A team of researchers in the neuroscience department at Case Western Reserve University School of Medicine believes they have found an answer: that a neural circuit involving spinal neurons and a signaling pathway are responsible for how burning pain is perceived.
They believe their discovery, recently published in the journal Neuron, could lead to a more effective treatment for chronic and pathological pain, such as stabbing, stabbing and burning pain, because it may involve the same signaling pathway.
We know that the stimuli of heat, cold, pressure and itching on our skin give rise to sensations appropriate to the brain. However, the neurons encoding the heat signals in the spinal cord were unclear. Our study identified a group of interneurons in the spinal cord needed for the sensation of heat. We also found that a signaling pathway contributes to heat hypersensitivity caused by inflammation or nerve damage. “
Hongsheng Wang, lead author of the study and postdoctoral fellow, Faculty of Medicine, Case Western Reserve University
The study
The brain controls everything we do, from our perception of the world around us to how our bodies move and experience sensations. The process involves neurons, which are cells that act as messengers to transmit information between the brain and the nervous system. Neurons send information through complex circuits throughout the body.
The research team analyzed spinal cord neurons and their role in thermal pain by analyzing mouse models and their response to heated plaques. During this process, the team identified the activation of a “novel” or newly discovered class of spinal cord neurons (called ErbB4 +) that process heat signals in the spinal cord.
They wanted to further investigate whether these neurons are specifically responsible for thermal pain. There are several ways to prove this, including the destruction of ErbB4 + neurons.
The researchers expressed a toxin specifically targeted to ErbB4 + neurons. Once the neurons were destroyed, the response to heat pain was affected. This showed that ErbB4 + neurons are specifically linked to how thermal pain is perceived, and when they are destroyed, the pain is no less felt.
The team also looked at the role of neuregulin 1 (NRG1), a protein involved in many cellular functions. They found that NRG1 and its receptor tyrosine kinase ErbB4 (often called NRG1 signaling) are also involved in the sensation of thermal pain.
The findings
“Pain is a sensation we have all experienced. For most of us, the pain is temporary,” said Lin Mei, a professor and chair of the Department of Neuroscience at the School of Medicine and author of the study. “However, for patients with pathological pain, the experience of pain is endless, with little hope of relief. Scientists have long believed that it is the result of dysfunctional neuronal activity.”
Mei said his study showed that pathological pain can be reduced by injecting an ErbB4 + inhibitor or an NRG1 neutralizing peptide.
The application of these findings may go beyond the therapeutic treatment of pathological pain.
“Both NRG1 and ErbB4 are at risk for many brain disorders, including major depression and schizophrenia,” Mei said. “Further studies are warranted to show whether the mechanism of heat pain and pathological pain also play a role in different types of pain experienced by those with brain disorders.”
Source:
Case Western Reserve University
Magazine reference:
Wang, H., et al. (2022) A new connection of spinal neurons for the sensation of heat. Neuron. doi.org/10.1016/j.neuron.2022.04.021