Abstract: Researchers have discovered a neural circuit involving spinal neurons and a signaling pathway that is responsible for how burning pain is perceived.
Source: Case Western Reserve
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 frying 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 is 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 shooting pain, stabbing and burning, because it may involve the same signaling pathway.
“We know that the stimuli of heat, cold, pressure and itching in our skin give rise to sensations in the brain. However, the neurons that encode the heat signals in the spinal cord were not clear,” said Hongsheng Wang. , lead author of the study and postdoctoral fellow at the School of Medicine.
“Our study identified a group of interneurons in the spinal cord needed for sensation of heat. We also found that a signaling pathway contributes to heat hypersensitivity caused by inflammation or nerve damage.”
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.
The team 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 brain controls everything we do, from our perception of the world around us to how our bodies move and experience sensations. Credit: The Researcher
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.
They also examined 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
“It simply came to our notice then. For most of us, the pain is temporary, “said Lin Mei, a professor and chair of the Faculty of Medicine’s Department of Neuroscience 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.”
About this pain research news
Author: Press Office Source: Case Western ReserveContact: Press Office – Case Western ReserveImage: Image is credited to researchers
See also
Original search: closed access. “A new connection of spinal neurons for the sensation of heat” by Hongsheng Wang et al. Neuron
Summary
A new connection of spinal neurons for the sensation of heat
Highlights
- ErbB4 + spinal neurons are activated by heat and synapsed by TRPV1 + nociceptors
- The sensation of heat is reduced by the ablation or inhibition of the neuron ErbB4 +
- Increased effect on heat sensation by inhibiting ErbB4 +, SST + and CCK + neurons together
- NRG1-ErbB4 signaling promotes heat sensation and hypersensitivity
Summary
The perception of heat allows for acute avoidance responses to prevent tissue damage and maintain body thermal homeostasis. Unlike other modalities, it is not clear how heat signals are processed in the spinal cord.
Using the unicellular gene profile, we identified ErbB4, a transmembrane tyrosine kinase, as a novel marker of heat-sensitive spinal neurons in mice. Ablation of the ErbB4 + neurons in the spine attenuates the sensation of heat.
These neurons receive monosynaptic inputs from TRPV1 + nociceptors and form excitatory synapses in target neurons. Activation of ErbB4 + neurons improves the heat response, while inhibition reduces the heat response.
We demonstrated that heat sensation is regulated by NRG1, an ErbB4 activator, and involves dynamic tyrosine kinase activity that promotes glutamatergic transmission.
Evidence indicates that NRG1-ErbB4 signaling is also implicated in the hypersensitivity of pathological pain.
Taken together, these results identify a spinal neuron connection formed by ErbB4 + neurons for heat sensation and reveal a regulatory mechanism by NRG1-ErbB4 signaling.