Fiery brain inflammation

Brain on Fire: How Inflammation Could Be Silently Sabotaging Your Health

Rhea Morgan in Health & Wellness December 2025 • 4 min read.

"New research reveals the surprising role of brain inflammation in common neurological issues, and what you can do about it."

For years, scientists recognized inflammation's role in diseases outside the brain. But now, they're uncovering its surprising impact within the central nervous system itself. Neuropeptide substance P (SP) and its receptor, neurokinin-1 receptor (NK-1R) are found at high levels in the CNS and is found to exacerbate inflammation.

The old view saw SP primarily as a pain messenger. Now, research indicates it worsens inflammation related to infections and other neurological problems. Blocking SP/NK-1R interactions reduces the severity of neuroinflammation and damage in animal models. This raises an important question: could tamping down this inflammatory pathway offer a new approach to protecting our brains?

This article explores the emerging link between SP/NK-1R and brain inflammation. We'll break down the science, reveal what triggers this inflammatory cascade, and discuss potential ways to protect your brain.

The SP/NK-1R Connection: How it Ignites Brain Inflammation

The study highlights that both human microglia and astrocytes, two critical types of brain cells, possess NK-1R. This means they are primed to respond to SP. The research further showed that the presence of bacterial pathogens or their components can ramp up NK-1R expression in these astrocytes, making them even more sensitive to SP.

Here's what happens when SP binds to NK-1R on these brain cells:

Microglia Activation: SP triggers the activation of NF-kB, a key protein complex that controls the production of inflammatory molecules.
Astrocytic Mayhem: SP amplifies the release of IL-6, a potent inflammatory cytokine, and increases the production of neurotoxic substances that can damage neurons.
A Vicious Cycle: This creates a feedback loop where inflammation worsens, potentially leading to neurological damage.

The researchers demonstrated that SP significantly increases the release of IL-6 when microglia and astrocytes are exposed to common bacteria known to cause CNS infections, including B. burgdorferi, N. meningitidis, S. pneumoniae and S. aureus. Furthermore, SP can also enhance the production of soluble mediators capable of inducing neuronal cell death by human astrocytes in response to either B. burgdorferi or S. pneumoniae, leading to neurotoxicity.

What This Means For You: Practical Takeaways and Future Directions

This research provides a compelling piece of the puzzle of neuroinflammation. While it's still early, it suggests that managing SP/NK-1R pathways could be a valuable target for interventions. Several questions remain:

<ul><li>What Triggers SP Release?: What everyday factors (stress, diet, environmental toxins) might increase SP levels in the brain?</li><li>Who is Most Vulnerable?: Are certain individuals genetically predisposed to overactive SP/NK-1R systems?</li><li>Can We Intervene?: Could lifestyle changes, targeted therapies, or specific diets help regulate this inflammatory pathway?</li></ul>

For now, the research underscores the importance of a holistic approach to brain health. By understanding the potential role of inflammation, we can be more proactive in protecting our cognitive function and overall well-being.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1186/s12974-017-1012-5, Alternate LINK

Title: Human Microglia And Astrocytes Constitutively Express The Neurokinin-1 Receptor And Functionally Respond To Substance P

Subject: Cellular and Molecular Neuroscience

Journal: Journal of Neuroinflammation

Publisher: Springer Science and Business Media LLC

Authors: Amanda R. Burmeister, M. Brittany Johnson, Vinita S. Chauhan, Megan J. Moerdyk-Schauwecker, Ada D. Young, Ian D. Cooley, Alejandra N. Martinez, Geeta Ramesh, Mario T. Philipp, Ian Marriott

Published: 2017-12-01

Everything You Need To Know

What is the main topic of the research discussed?

The study focuses on the role of brain inflammation in neurological issues. It highlights the involvement of the neuropeptide substance P (SP) and its receptor, neurokinin-1 receptor (NK-1R), within the central nervous system (CNS). Inflammation, previously recognized for its role in diseases outside the brain, is now understood to have significant impact within the CNS, potentially affecting mood and cognitive function.

What is the role of Substance P (SP) and neurokinin-1 receptor (NK-1R) in the context of this research?

Substance P (SP) and neurokinin-1 receptor (NK-1R) exacerbate brain inflammation. Both human microglia and astrocytes, key brain cells, possess NK-1R. When SP binds to NK-1R, it triggers the activation of NF-kB in microglia, which controls the production of inflammatory molecules. In astrocytes, SP amplifies the release of IL-6, a potent inflammatory cytokine, and increases the production of neurotoxic substances, leading to neurological damage.

Can you explain the process by which Substance P (SP) and neurokinin-1 receptor (NK-1R) contribute to brain inflammation?

The binding of Substance P (SP) to the neurokinin-1 receptor (NK-1R) on microglia and astrocytes initiates a cascade of inflammatory events. This includes microglia activation, where NF-kB is activated to produce inflammatory molecules. Simultaneously, astrocytes release IL-6 and neurotoxic substances, leading to a worsening cycle of inflammation. This process can potentially lead to neurological damage. The inflammatory response can be triggered or amplified by the presence of pathogens.

What are the potential implications of managing the Substance P (SP)/neurokinin-1 receptor (NK-1R) pathways?

Blocking the interaction of Substance P (SP) and neurokinin-1 receptor (NK-1R) shows promise in reducing neuroinflammation and damage in animal models. This pathway could be a new approach to protecting the brain. While it's still early, managing SP/NK-1R pathways may become a valuable target for interventions. This research suggests that understanding and controlling this inflammatory pathway could lead to new therapeutic strategies.

Which specific bacteria are mentioned in connection to brain inflammation?

The article mentions several bacteria, including B. burgdorferi, N. meningitidis, S. pneumoniae, and S. aureus, as examples that can exacerbate brain inflammation. The presence of these bacterial pathogens, or their components, can increase the expression of neurokinin-1 receptor (NK-1R) in astrocytes, making them more sensitive to Substance P (SP). This heightened sensitivity can amplify the inflammatory response, as detailed in the article, making these bacteria relevant to the discussion of neuroinflammation.