Hunger, Fear & Pain: How the Brainstem Reveals a New Path for Chronic Pain Relief
Oct 14, 2025
A 2025 study published in Nature has uncovered an extraordinary mechanism in the human brainstem: a neural “hub” that decides whether your body feels pain — or ignores it altogether.
Researchers discovered a set of neuropeptide Y1 receptor (Y1R) neurons in the lateral parabrachial nucleus (lPBN) that regulate enduring pain signals. When survival demands like hunger, thirst, or fear rise, these Y1R neurons are suppressed, allowing the brain to pause pain so you can focus on staying alive.
For patients across Phoenix, Scottsdale, Tempe, and Chandler, this insight represents a new frontier in pain medicine — and hope for treatments that can modulate pain at its very source, within the brainstem itself.
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Chronic pain affects over 50 million Americans — yet conventional medicine often stops at treating symptoms instead of causes. At CNS, we specialize in decoding how the brain, spinal cord, and peripheral nerves interact to generate pain, and how new neuroscience discoveries can reshape recovery.
The Nature (2025) study demonstrates that pain is not merely a sensory event — it’s a state of the brain.
The lateral parabrachial nucleus, a small brainstem structure connecting sensory input to emotional response, acts as a switchboard for persistent pain. When Y1R neurons remain active after injury, they keep the body “locked” in a pain loop even after tissue healing.
At CNS, Dr. Leslie Zuniga and our multidisciplinary team integrate these insights into practical care pathways. By recognizing pain as a dynamic neural state, CNS clinicians can target treatment more precisely — reducing unnecessary medication and improving function.
Dr. Leslie Zuniga, a board-certified neurologist with advanced training in general and headache neurology, leads CNS’s approach to chronic and neuropathic pain. She emphasizes patient education, empowering individuals to understand how their nervous system regulates discomfort, mood, and motivation.
“Pain is never just in the body — it’s also in how the brain interprets danger and survival,” says Dr. Zuniga. “The more we learn about pain circuits, the better we can help patients retrain their nervous systems to feel safe again.”
Comprehensive neurodiagnostic testing (EEG, EMG, MRI coordination)
Pain syndrome specialization for neuropathy, fibromyalgia, and post-stroke pain
Research-driven protocols informed by Nature, NIH, and Mayo Clinic studies
Collaborative care linking neurology, physical therapy, and behavioral medicine
Personalized plans balancing medications, non-invasive stimulation, and mind-body interventions
CNS serves patients throughout the Valley — including Phoenix, Scottsdale, Mesa, Gilbert, and Peoria — helping Arizonans rediscover movement and clarity after years of persistent pain.
The brainstem’s pain hub, as identified in the 2025 study, helps explain why some patients continue to hurt long after an injury heals. This phenomenon is called central sensitization — where neurons in the spinal cord and brain become overactive and amplify pain signals.
Common conditions that involve these circuits include:
Neuropathy from diabetes or nerve compression
Complex regional pain syndrome (CRPS)
Post-stroke pain or thalamic pain syndrome
Fibromyalgia
Tension and migraine-related headaches
Chronic back and neck pain unrelated to structural damage
Pain becomes chronic when it lasts more than three months or outlasts tissue healing. Other red flags include:
Sensations that spread beyond the original injury
Pain accompanied by fatigue, insomnia, or brain fog
Heightened sensitivity to touch, temperature, or light
Emotional distress or fear associated with movement
Recognizing these patterns early helps CNS neurologists distinguish between structural damage and neural circuit dysfunction — the first step toward effective pain reversal.
The new research shows that pain is not a fixed signal but a fluid state modulated by survival needs. In the study, when animals experienced hunger or fear, their brains released neuropeptide Y (NPY), which suppressed pain-generating neurons in the parabrachial region.
This reveals why people under acute stress sometimes don’t feel injuries until after the threat passes. The same mechanism, when dysregulated, may trap patients in a state where pain persists even without danger.
Understanding these connections allows CNS to design care that addresses both the neurological and psychological aspects of chronic pain.
CNS follows a structured, multi-layered approach to pain diagnosis — combining state-of-the-art neurodiagnostic testing with clinical insight to identify the true source of pain.
| Test | Purpose | Availability at CNS |
|---|---|---|
| MRI Brain & Spine | Rules out lesions, tumors, or MS-related damage | Partnered Phoenix imaging centers |
| EEG Testing Phoenix AZ | Measures abnormal brain activity in headache or seizure-related pain | On-site EEG suite |
| EMG Testing Phoenix | Detects nerve compression or neuropathy | On-site testing by CNS technologists |
| Nerve Conduction Studies (NCS) | Quantifies nerve signal speed and strength | Same-day results |
| Autonomic Testing | Evaluates dysautonomia and circulatory pain responses | Advanced lab equipment |
| Pain Questionnaires & Functional Assessments | Tracks how pain affects daily life and mood | Administered at each visit |
The 2025 study used optogenetic and imaging tools to map how Y1R neurons connect to other pain centers like the amygdala and hypothalamus. At CNS, we translate these research methods into clinical practice through advanced MRI protocols and functional imaging, which can reveal changes in neural connectivity linked to chronic pain.
Patients undergoing brain scans often receive a comprehensive explanation of findings, including which regions may be over-signaling pain responses and how therapy can help rebalance those circuits.
“Pain is not always a signal of damage — sometimes it’s a sign that the brain’s protective systems have become over-protective,” Dr. Zuniga explains. “Our goal is to teach the nervous system to feel safe again.”
This philosophy informs CNS’s integrated pain diagnostic model, where objective tests meet empathetic clinical listening. Each result becomes a map for healing — not just a report of what’s wrong.
For decades, chronic pain was viewed as an unavoidable outcome of tissue injury or degeneration. But the 2025 Nature study revealed a deeper truth — that the brainstem acts as a central gatekeeper controlling whether pain persists or fades.
By targeting these circuits — specifically the neuropeptide Y1 receptor (Y1R) neurons within the lateral parabrachial nucleus (lPBN) — researchers have identified new ways to silence pain that remains even after healing.
At CNS, we integrate this evolving understanding into our Phoenix neurology practice, offering both traditional and emerging strategies to reduce pain while improving overall nervous system health.
These remain the foundation of evidence-based pain management and are customized to each patient’s neurological profile.
a. Pharmacologic options:
Anti-neuropathic agents: Gabapentin, pregabalin, duloxetine, and amitriptyline target nerve hyperactivity.
Anti-inflammatory medications: Used short-term for inflammatory pain or post-injury flare-ups.
Muscle relaxants: Cyclobenzaprine or baclofen for tension and spasticity.
Targeted injections: Occipital nerve blocks or trigger point therapy.
Botulinum toxin injections: For migraine or focal dystonia management.
b. Interventional options:
Epidural steroid injections or facet joint blocks for radicular or spinal pain.
Spinal cord stimulation — a minimally invasive implant that modulates pain signals.
Peripheral nerve stimulation (PNS) for localized neuropathy.
The Nature study reinforces that the brainstem’s Y1R neurons can override chronic pain when properly stimulated — an insight that aligns with the success of neuromodulation technologies already used at CNS.
Neuromodulation devices deliver mild electrical impulses to targeted nerves or spinal regions, retraining pain circuits and restoring normal signal balance.
This mirrors what neuropeptide Y does naturally — calming overactive neurons and resetting pain perception.
Transcranial Magnetic Stimulation (TMS) for chronic headache, neuropathic pain, and depression-linked pain circuits.
Vagus Nerve Stimulation (VNS) for refractory pain and autonomic dysfunction.
Peripheral Nerve Stimulation (PNS) for focal nerve injuries and CRPS.
By combining stimulation therapies with research-backed pain science, CNS offers Arizona patients a window into next-generation neural recovery.
Dr. Leslie Zuniga and the CNS team emphasize the critical role of the mind–brain connection in chronic pain. The same brainstem circuits that process fear and hunger also influence pain modulation — making emotional and cognitive therapies a key part of recovery.
CNS Integrative Pain Program includes:
Cognitive Behavioral Therapy (CBT): Rewires fear–pain associations in the cortex.
Mindfulness-based stress reduction: Deactivates limbic overdrive contributing to pain persistence.
Biofeedback and breathing training: Improves autonomic control over heart rate, temperature, and muscle tone.
Neurofeedback: Real-time EEG-guided therapy to retrain maladaptive brain patterns.
These methods complement medical treatment and align directly with the 2025 findings that pain is deeply connected to need-state control — where emotional safety and physiological balance can literally deactivate pain neurons.
Life in Arizona brings unique opportunities and challenges for those managing chronic pain. Our desert environment, heat, and sunlight exposure can influence pain, fatigue, and hydration in subtle but significant ways.
Dehydration and heat stress increase inflammation and can heighten nerve sensitivity.
CNS Recommendations:
Maintain steady hydration — aim for 80–100 ounces of water daily.
Add electrolytes if outdoors or exercising.
Use cooling towels or vests during hot months (May–September).
What you eat directly impacts your nervous system’s inflammatory state.
Pain-lowering foods:
Omega-3-rich fish (salmon, sardines)
Turmeric, ginger, and dark leafy greens
Berries, olive oil, and walnuts
Foods to limit:
Processed sugars, refined carbs, and trans fats
Excess caffeine or alcohol, which may increase stress signaling
Gentle, consistent activity improves blood flow, strengthens the spine, and reduces neuroinflammation.
Best Arizona-friendly exercises:
Early-morning walks or pool therapy
Chair yoga and light resistance bands
Tai Chi for coordination and balance
The lateral parabrachial nucleus also regulates arousal and sleep, meaning poor sleep worsens pain perception.
Aim for 7–8 hours nightly.
Keep a consistent bedtime routine.
Limit blue-light exposure before bed.
Chronic pain and fear share neural pathways. Just as hunger suppresses pain through NPY release, a calm emotional state can shift your brain out of “survival mode.”
CNS offers relaxation techniques and guided imagery exercises to lower the brain’s threat response — one of the most evidence-based ways to reduce long-term pain.
At CNS, we believe in pairing compassionate care with rigorous science. Our team tracks emerging pain studies across institutions like Nature, NIH, and Mayo Clinic to ensure every treatment aligns with current neurobiology.
Translating preclinical findings, such as the Y1R neuron discovery, into future human applications.
Collaborating with Arizona Neuroscience Research for potential study participation.
Using research-based tools to refine EEG and EMG protocols for chronic pain mapping.
Providing second opinions on complex neuropathic and spinal cases.
When pain becomes chronic, a second neurological perspective can uncover overlooked causes — or offer access to new treatments like neuromodulation or clinical research trials.
CNS second opinions emphasize clarity, patient education, and forward-looking solutions rather than medication dependency.
1. What is the parabrachial nucleus, and why is it important?
It’s a brainstem region that connects sensory pain signals to emotional and survival circuits. The 2025 Nature study found that it can “store” pain long-term unless reset by specific neurochemical triggers like neuropeptide Y.
2. What does this discovery mean for patients with chronic pain?
It suggests pain is reversible — not permanent. Therapies that target Y1R or NPY pathways could retrain the brain to turn off unnecessary pain signals.
3. How does CNS use this information clinically?
We apply it through neuromodulation, behavioral therapy, and advanced diagnostics that assess how brain and spinal circuits communicate.
4. Is this related to emotional or psychological pain?
Yes, indirectly. Fear, stress, and hunger all interact with the same brainstem hubs, showing that chronic pain involves both biological and emotional dimensions.
5. What if medications haven’t worked for me?
That’s common. CNS specializes in patients with refractory pain — those who didn’t respond to standard treatments — offering advanced testing and non-opioid alternatives.
6. Can mindfulness or relaxation really help pain?
Yes. Calming survival circuits reduces brainstem activation and lowers inflammation, which translates to measurable pain reduction.
7. Is this new research only for lab models?
Currently yes, but it opens pathways for human treatments targeting Y1R neurons through electrical, pharmacologic, or gene-based methods.
8. What Arizona-specific factors affect chronic pain?
Dehydration, extreme heat, and vitamin D fluctuations can worsen nerve pain — all factors CNS addresses during personalized care planning.
9. How long does it take to feel improvement?
With consistent care and active participation, most CNS patients experience measurable improvement within 4–12 weeks.
10. Can I get a second opinion if I already have a neurologist?
Absolutely. Many Phoenix-area patients come to CNS for a fresh perspective or advanced testing unavailable elsewhere.
If you or a loved one are living with persistent pain, don’t wait for it to define your life.
At the Center for Neurology & Spine, we combine neuroscience, compassion, and precision to help you rediscover comfort and confidence.