"Doctor, I could feel the pain and heard you talking while you were operating on me."

The young woman had just regained consciousness. Standing beside her bed, Chong Chen felt a chill of recognition. During the surgery, he had sensed that something was wrong: Despite standard anesthetic dosing, her heart rate and blood pressure remained elevated. Now he understood. She had experienced intraoperative awareness.

In modern general anesthesia, three classes of drugs are typically administered in combination: sedatives to induce unconsciousness, analgesics to block pain, and muscle relaxants to prevent movement. In rare cases, a patient may remain conscious despite adequate sedation and analgesia. Paralyzed by muscle relaxants, they cannot speak or move, even as they feel pain.

"That racing heart rate and blood pressure were signs of her struggling in silence," Chen recalled.

For Chen, the experience marked a turning point. He left clinical practice and stepped into the laboratory.

Chong Chen earned his medical degree from Wenzhou Medical University in 2009 and began his residency in anesthesiology at its Second Affiliated Hospital and Yuying Children's Hospital. Yet the unanswered questions surrounding anesthesia lingered. He went on to complete a master's degree at Shanghai Jiao Tong University (2011–2014), then moved to Europe to pursue a Ph.D. at the Institute of Science and Technology Austria under Peter Jonas, a professor and leading authority on synaptic transmission.

In 2018, Chen joined Gregory Scherrer's lab at Stanford University, relocating with the group to the University of North Carolina in 2019. In June 2025, he returned to China as a full-time assistant professor and Ph.D. supervisor at the Westlake University School of Medicine.

A decade after leaving the hospital, the former anesthesiologist had come back, not to administer anesthesia, but to interrogate pain itself.

The Overlooked Guardian in the Operating Room

In China, anesthesiology remains an underappreciated specialty. During surgery, while the surgeon concentrates on the pathology, the anesthesiologist monitors the patient's vital signs, such as heart rate, respiration, blood pressure, and temperature, guarding life moment by moment.

Clinically, anesthesiology is a mature discipline. Yet scientifically, many mechanisms of anesthetic drugs remain obscure. How does consciousness disappear? How does it return? The neurobiology underlying these transitions is still being unraveled.

After the intraoperative awareness case, Chen found himself visiting the patient repeatedly, worried about long-term psychological trauma. Though she insisted she was fine, Chen was not convinced. To be trapped in pain, unable to signal distress, is an experience that defies easy reassurance.

He also began to question routine practice. Dosages of sedatives and analgesics often rely heavily on clinical experience and population averages. But what neural principles govern their effects? When Chen began searching for doctoral laboratories, he discovered how little fundamental research addressed anesthesia.

That search led him to Professor Peter Jonas, who studied synaptic transmission in GABAergic neurons. Gamma-aminobutyric acid (GABA), the brain's principal inhibitory neurotransmitter, is deeply implicated in anesthetic mechanisms. The connection was irresistible.

Chen completed his Ph.D. in just over three and a half years. His surgical training proved unexpectedly advantageous in performing delicate paired neuronal recordings under the microscope. Years later, Jonas would remark at a conference that Chen still held the institute's record for Ph.D. graduation.

The Abyss of Pain

Before one can understand anesthesia, one must confront pain.

Unlike vision or hearing, which map relatively clearly to specific cortical regions, pain is distributed across widespread neural networks. It is notoriously difficult to define. In 2020, the International Association for the Study of Pain revised its definition to "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage."

The inclusion of "actual or potential" is striking. Few scientific definitions accommodate such subjectivity.

Consider phantom limb pain. Patients may experience throbbing or stabbing sensations in a limb that no longer exists. The pain can be persistent or episodic. The precise mechanisms remain debated. "It may represent a persistent memory of pain," Chen suggested.

Pain assessment presents further complications. Clinical scoring systems rely largely on self-reporting. Although widely used, such subjective measures complicate the diagnosis and treatment of chronic pain. In an era marked by opioid overuse and dependence, the absence of objective metrics increases the risk of overprescription.

Over time, Chen became convinced that the key to pain modulation lies within the brain itself.

Everyday experience hints at an internal pain-control system. Expectation shapes perception. The placebo effect illustrates this phenomenon.

During World War II, anesthetist Henry Knowles Beecher famously administered saline to wounded soldiers when morphine supplies ran out. To his astonishment, many soldiers reported substantial pain relief. Belief had altered experience.

But how does expectation translate into neural activity?

During his postdoctoral work, Chen designed an experiment using lab rats. He built two connected chambers: one with a floor heated to 48℃, the other at a comfortable 30℃. Naturally, the rats fled the hotter chamber. After several days of conditioning, they learned that entering the cooler chamber brought relief.

In the critical test phase, both chambers were set to 48℃. Yet when rats entered the chamber previously associated with relief, they exhibited significantly fewer pain behaviors, such as paw licking and jumping, compared to the control group.

Above the chambers, fine wires connected to the rats' brain enabled calcium imaging, allowing researchers to visualize neuronal activity through fluctuations in the intracellular calcium levels. Surprisingly, initial analyses revealed no obvious neural signature corresponding to the behavioral placebo effect.

Chen was stuck for months. Calcium imaging generated vast datasets requiring machine-learning algorithms for interpretation. Then came a realization: He had misdefined the onset of expectation. It did not begin when the rats stepped into the cooler chamber. Expectation had formed during training.

After recalibrating the analysis window, machine-learning quickly detected a distinct neural signature of placebo analgesia. In 2024, Chen published this finding in Nature, identifying a specific neural circuit: neurons in the rostral anterior cingulate cortex (rACC) projecting to the pontine nucleus (rACC→Pn). This study demonstrated that expectation-driven pain relief was encoded at the level of defined circuits and synapses.

It was a milestone, but also just a beginning.

"The placebo pain relief proves that the body possesses a complete endogenous pain-relief system," said Chen. "We are yet to fully harness it." Positive expectation activates specific neural pathways that reduce pain perception. This finding lends biological support to non-pharmaceutical pain relief such as cognitive behavioral therapy and yoga, which also sheds light on a future with less opioid dependence.

Pain is not merely sensory. It is entwined with emotion, identity, and dignity. As physician Edward Trudeau famously said, "To cure sometimes, to relieve often, to comfort always."

"Medicine is never just about curing," Chen reflected. "It is also about companionship and support."

Returning to the Bedside

Now, after a decade devoted to research, Chen is returning to clinical work at the Westlake University School of Medicine Affiliated Hangzhou First People's Hospital. His research portfolio still includes intraoperative awareness—an unresolved question that first propelled him into science.

In conversation, he speaks of collaborations with colleagues in anatomy and oncology, of emerging evidence that certain cancers form functional synapses with neurons, drawing growth signals from the nervous system. The boundary between mind and body grows ever thinner.

Confronting another person's pain is never easy, Chen acknowledges. But it is precisely that encounter—standing at the intersection of consciousness and suffering—that defines his vocation.

Pain may resist simple explanation. Yet in tracing its circuits from the operating room to the synapse, Chong Chen continues to search for a deeper understanding of how we lose awareness, how we feel, and how we heal.

An Invitation to Join Chong Chen’s Lab

Chong Chen's laboratory focuses on the neurobiological mechanisms of placebo analgesia and has advanced understanding of pain modulation to the level of circuits, cells, and synapses.

Over the next five years, the lab will concentrate on three major research directions:

1. Dissecting the neural basis of placebo analgesia

2. Investigating the endogenous opioid system in the cerebellum and its roles in pain and opioid-related psychiatric disorders

3. Exploring the neurobiology of anesthesia emergence

The lab welcomes applications from assistant researchers, postdoctoral fellows, and research assistants. Candidates with backgrounds in molecular biology, cellular biology, systems neuroscience, computational neurobiology, anesthesiology, and related disciplines are encouraged to apply. The team aims to cultivate a collaborative, intellectually rigorous environment dedicated to original, high-quality research.

Email: chenchong@westlake.edu.cn

Lab's webpage: www.cchenlab.org