Melatonin and Ambien before surgery may improve sleep, reduce pain and opioid use after surgery

American Society of Anesthesiologists

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Key Takeaways:

• Taking melatonin or Ambien before surgery may do more than improve sleep. They may reduce anxiety, lower postoperative pain, restore normal circadian rhythms and decrease opioid requirements after surgery, an analysis suggests.
• Study authors found melatonin may offer broader benefits than Ambien, while Ambien may be most effective for patients with preexisting insomnia.
• Patients who sleep better before surgery may experience less pain and require fewer opioids during recovery.

SAN DIEGO — Improving sleep before surgery through the use of melatonin or Ambien (zolpidem) may ease presurgical anxiety, reduce pain after surgery, decrease opioid requirements and help patients recover better, according to an analysis of 25 years of research presented at the ANESTHESIOLOGY® 2026 annual meeting.

Poor sleep and anxiety are common before surgery and can contribute to heightened pain sensitivity, increased opioid use and slower recovery. In the studies, patients typically took melatonin the night before surgery and/or 20 to 90 minutes before anesthesia. Ambien was taken at bedtime, either the night before surgery or on multiple nights beginning up to two days before surgery. The findings suggest that addressing sleep may be a modifiable part of preparing for surgery that helps support recovery.

“While we usually focus on what happens in the operating room, our review suggests we may be overlooking a critical window for improving outcomes in the nights before surgery,” said Sebastian Amaya, M.D., senior author of the study and an anesthesiology resident at Yale School of Medicine, New Haven, Connecticut. “Our paper is unique because it focused exclusively on pre-surgery-only use of melatonin or Ambien, showing that something as simple as improving sleep before a procedure can help patients have a more comfortable recovery while reducing the need for heavy painkillers and their potential risks.”

The researchers analyzed 16 studies of patients undergoing abdominal, gynecologic, orthopedic, urologic, dental and other surgical procedures published between 2000 and 2025, which included a total of more than 1,100 patients. Melatonin doses ranged from 1 to 20 mg, while Ambien was consistently dosed at 10 mg.

Across the studies, melatonin, a naturally occurring hormone that helps regulate sleep, was associated with less anxiety, pain and inflammation, as well as more than a 30% reduction in opioid use in some abdominal surgery patients. Studies using wrist-worn activity monitors also suggested melatonin helped patients return to more normal patterns of sleep and daytime activity during recovery. The review also suggested that melatonin may offer advantages over traditional sedatives for older adults who may be more vulnerable to confusion after surgery.

Ambien, a commonly prescribed sleep medication, helped patients with preexisting sleep problems sleep better before surgery and was linked to less pain after. The idea is that by helping patients get more normal, restorative sleep before the physical stress of surgery, it may indirectly improve how they experience pain and recover afterward. Patients undergoing colorectal surgery needed less opioid pain medication during and in the first 24 hours after the procedure and also had lower levels of certain inflammatory markers. Patients undergoing hip replacement reported less anxiety and depression and greater satisfaction with their recovery, researchers said.

“Melatonin may be particularly valuable for patients who experience significant anxiety before surgery, those at higher risk for respiratory complications and older adults who may be vulnerable to cognitive side effects from traditional sedatives,” said Dr. Amaya. “Ambien may be better suited for patients with preexisting insomnia or significant sleep disruption.”

*** ANESTHESIOLOGY 2026 news releases may contain updated data that was not originally available at the time abstracts were submitted.

THE AMERICAN SOCIETY OF ANESTHESIOLOGISTS
Founded in 1905, the American Society of Anesthesiologists (ASA) is an educational, research and scientific society with more than 62,000 members organized to advance the medical practice of anesthesiology and secure its future. ASA is committed to ensuring anesthesiologists evaluate and supervise the medical care of all patients before, during and after surgery. ASA members also lead the care of critically ill patients in intensive care units, as well as treat pain in both acute and chronic settings.

For more information on the field of anesthesiology, visit the American Society of Anesthesiologists online at asahq.org. To learn more about how anesthesiologists help ensure patient safety, visit asahq.org/madeforthismoment. Join the #ANES26 conversation on social media. Follow ASA on Facebook, X, Instagram, Bluesky and LinkedIn.

 

With a flick of a switch: Reducing addiction risk from opioid painkillers

Penn’s Dirk Trauner and collaborators have developed a platform that allows opioid activity to be turned ‘on’ or ‘off’ with the flick of a light switch, paving the way for bypassing opioid addiction and other adverse side effects

University of Pennsylvania

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Joshua Levitz (left), biochemistry and biophysics professor at Weill Cornell Medicine, and Dirk Trauner, the George A. Weiss University Professor and a Penn Integrates Knowledge Professor with joint appointments in the Department of Chemistry in the School of Arts & Sciences and the Department of Systems Pharmacology and Translational Therapeutics in the Perelman School of Medicine.

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Credit: University of Pennsylvania and Weil Cornell Medicine

Last year, more than 40,000 Americans died from overdoses involving opioids, according to the Centers for Disease Control and Prevention.

Opioid compounds, including morphine, codeine, and fentanyl, exert most of their effects by activating mu-opioid receptors, which are found throughout the brain and in the spinal cord, peripheral nerves, and gut. These compounds can be very potent painkillers, but their bodywide activity leads to side effects including constipation, tolerance (the need for higher and higher doses), addiction, and—potentially fatally—the suppression of brain signals that control breathing.

Eliminating or at least greatly reducing side effects would mean targeting the activity of opioid painkillers very selectively to the neurons or nerve fibers where they are needed.

In a new paper published in Cell, chemist and pharmacologist Dirk Trauner and collaborators at Weill Cornell Medicine and the University of Southern California present an experimental opioid painkiller designed to be reversibly switched “on” and “off” with different light frequencies to keep its action local and out of the brain. Their findings may eliminate the dangerous side effects that characterize current opioids.

“It would be terrible if we would deprive people suffering from debilitating pain from opioids, because they’re too important and effective for that,” says Trauner, a Penn Integrates Knowledge Professor in the School of Arts & Sciences and the Perelman School of Medicine. “Yet, you want to make them safer, and that’s our main goal here.”

The work builds on two decades of research in Trauner’s lab on controlling biology with light. In 2004, Trauner and colleagues at the University of California, Berkeley, used a synthetic azobenzene switch to turn the firing of neurons on and off with light.

The paper appeared months before a landmark study by Karl Deisseroth and colleagues that helped define and establish optogenetics, the use of light to control the activity of nerve cells—a field that was recognized with this year’s Nobel Prize in Physiology or Medicine. Trauner notes that the early history highlights the crucial role chemistry played in the field’s origins.

“The idea of light-switchable receptor activators has been around for 20 years or so, but I think these results represent a major step forward,” says study co-senior author Joshua Levitz, a professor of biochemistry and biophysics at Weill Cornell Medicine.

Creating a light switch

Using azobenzenes, organic compounds that can stably and reversibly change their shape when exposed to certain light frequencies, the team designed several morphine-azobenzene compounds that engage the mu-opioid receptor differently depending on the light to which they’ve been exposed.

One of these compounds, AM-3, worked just as they had hoped, activating the mu-opioid receptor strongly when in a shape induced by near-ultraviolet light but weakly when in a shape induced by blue light.

The researchers showed that with this “photopharmacology” approach, they could activate AM-3’s painkilling effect only where needed, allowing substantial pain relief without side effects such as tolerance or constipation in multiple preclinical pain models, including cancer pain models. AM-3 cannot cross into the brain easily, helping to minimize brain-based side effects such as addiction and respiratory suppression.

“We think this is a significant breakthrough not just for pain management but also for the general strategy of photopharmacology, which has a great many potential applications in biology and medicine,” says Levitz.

Looking ahead

The teams hope to take their approach through further preclinical development and ultimately to clinical trials. The researchers are working on successor molecules that are switchable with safer light frequencies than ultraviolet light, which can damage eyes and skin.

“Next is to make them adaptable for humans,” says Trauner. “Our goal is to make them sensitive toward long wavelengths like red light, which can deeply penetrate skin and tissue. We need to improve the photochemistry, but we have some pretty good ideas on how to do this. In fact, we have some exciting preliminary results already.”

Weill Cornell Medicine contributed to this news release.

Dirk Trauner is the George A. Weiss University Professor and a Penn Integrates Knowledge Professor with joint appointments in the Department of Chemistry in the School of Arts & Sciences and the Department of Systems Pharmacology and Translational Therapeutics in the Perelman School of Medicine at the University of Pennsylvania.

Joshua Levitz is a professor of biochemistry and biophysics at Weill Cornell Medicine.

Other authors include Xiang Ji and Kenny Calderon-Godinez of Penn Arts & Sciences; Luca Posa, Giovanna R. Romano, Sheida Sharghi Moshtaghin, Anisul Arefin, Alberto J. Gonzalez-Hernandez, Ipsit Srivastava, and Kristen E. Pleil of Weill Cornell Medicine; Saif Khan, Antonina L. Nazarova, Gye Won Han, Saheem A. Zaidi, Zixin Zhang, Aaliyah S. Tyson, Mohsen Ranjbar, Vsevolod Katritch, and Cornelius Gati of the University of Southern California; Bruno Paz of New York University and the University of São Paulo; and Kanupriya Pande of Lawrence Berkeley National Laboratory.

This research was supported by the National Institutes of Health (grants R61/R33DA051529, R35GM150982, R01AT012075, R35GM153437, T32GM132081, and R36DA064987), the Rohr Family Research Scholar Award, the Monique Weill-Caulier Award, and the Charles H. Revson Fellowship.

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Journal

Cell

DOI

10.1016/j.cell.2026.09.042

Method of Research

Experimental study

Subject of Research

Animals

Article Title

An opioid efficacy switch for reversible optical control of analgesia

Article Publication Date

15-Oct-2026

COI Statement

L.P., G.R.R., V.K., D.T., and J.L. are inventors on a provisional patent application on the use of photoswitchable morphines for pain treatment.

 

The pain-sensing receptor behind chili-pepper burn may hold clues to pain treatments

New study finds the body's capsaicin receptor, TRPV1, responds differently to varying triggers

University of California - Davis Health

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By showing how capsaicin receptors respond to triggers, Jie Zheng hopes to open the door to new pain medicines. 

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Credit: UC Regents

Scientists have long known that capsaicin, the ingredient that makes chili peppers feel hot and is used in some pain-relief creams, works by activating a pain-sensing receptor known as TRPV1.

New research from the UC Davis School of Medicine reveals that the receptor does not respond to every trigger in the same way. Instead, different stimuli appear to place TRPV1 into distinct functional states. The finding opens new possibilities for more targeted pain treatments.

The study, published in PNAS (Proceedings of the National Academy of Sciences), was led by researchers in the UC Davis Department of Physiology and Membrane Biology. The findings challenge a longstanding assumption that TRPV1 adopts a single activated state regardless of what triggers it.

TRPV1 as a potential target for pain medicine

TRPV1 is often called the body's capsaicin receptor. Located on pain-sensing nerve cells, it detects heat, tissue injury, inflammation and chemical compounds — including the capsaicin in hot peppers.

Because TRPV1 plays a central role in pain pathways and does not involve opioid signaling, it has long been considered a potential target for developing nonaddictive pain medicines. However, efforts to block the receptor have been complicated by its equally important role in regulating body temperature.

"Researchers have generally assumed that once TRPV1 is activated, the channel enters essentially the same open state regardless of what stimulus triggered it," said first author Bo Hyun Lee, a former researcher in the Zheng Lab at UC Davis. "Our findings show that the receptor is more sophisticated than that. Different stimuli appear to stabilize different open states, each with distinct functional properties."

Methods measured receptor’s response to different stimuli

To investigate how TRPV1 responds to different stimuli, the researchers measured electrical currents passing through individual channels activated by:

• Capsaicin, the compound that gives chili peppers their heat
• Resiniferatoxin, an extremely hot compound derived from a succulent plant
• Hydrogen ions (protons), which create acidic conditions commonly associated with tissue injury and inflammation
• 2-APB, a chemical commonly used to modify ion channel activity
• Heat

They found that different activators consistently produced different conductance levels. This finding suggests the channel opens in distinct ways rather than entering a common activated state.

Modeling of the different states of the TRPV1 pore, including closed (left), capsaicin-activated (middle) and 2-APB-activated (right).

The team then combined several approaches to see if those different conductance levels reflected structural differences in the receptor itself.

Using sensitive ion-permeation measurements (which measure how quickly charged particles move across a barrier), the researchers detected evidence that different activators altered the shape of the channel pore. They also used a fluorescence-based technique in living cells that allowed them to watch different parts of the channel protein shift position as it responded to different stimuli.

Finally, computational modeling helped visualize how the receptor's structure changed when activated by different stimuli.

Together, these approaches pointed to the existence of multiple distinct open configurations of TRPV1.

"We were able to see consistent evidence from several independent experimental methods that the pore of the channel does not look exactly the same when activated by different stimuli," said senior author Jie Zheng, professor in the Department of Physiology and Membrane Biology. "That convergence of evidence gave us confidence that these are genuine functional states rather than experimental artifacts."

The researchers also made another unexpected discovery. When two stimuli were applied together, the channel opened more slowly instead of more quickly. The finding suggests that different activation mechanisms may sometimes interfere with one another, revealing an additional layer of complexity in how pain signals are processed.

By showing how capsaicin receptors respond to triggers, Jie Zheng hopes to open the door to new pain medicines. 

Findings may have implications for pain and basic research

Previous attempts to target TRPV1 with drugs for pain relief have often caused unwanted side effects, including major disruptions in body temperature regulation. The new study suggests it may someday be possible to selectively target receptor states associated with painful stimuli while preserving those involved in normal heat sensation.

"Our study provides a conceptual framework for thinking about TRPV1 in a much more nuanced way," said Vladimir Yarov-Yarovoy, co-author and professor in the Department of Physiology and Membrane Biology. "If different forms of activation produce different functional states, we may eventually be able to design therapies that selectively affect pain-related activity while leaving other essential functions intact."

The study also offers insight into how proteins function when encountering nontypical stimuli.

The work provides a new understanding of one of the body's most important pain sensors. It offers a potential roadmap for developing safer, more precise analgesic therapies. More research is needed to translate the study’s findings into new treatments.

Additional authors include Shisheng Li, Simon Vu, and Zhihao Yao from UC Davis and Yuhua Tian from UC Davis and Qingdao University.

Resources

• Read the study in PNAS
• Zheng Lab
• UC Davis Department of Physiology and Membrane Biology
• Read more about federal research at UC Davis

 

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Journal

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2614335123

Method of Research

Experimental study

Subject of Research

Cells

Article Title

Distinct functional open states of the polymodal nociceptor TRPV1

Article Publication Date

15-Oct-2026

Modeling of the different states of the TRPV1 pore, including closed (left), capsaicin-activated (middle) and 2-APB-activated (right).

Credit

UC Regents.

 

Patients with opioid use disorder diagnoses increased almost 33 percent from 2022 to 2025

FAIR Health releases annual update of Opioid Tracker, an interactive tool tracking opioid use disorder nationally and state by state

FAIR Health

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Top Five Procedure Code Categories by Utilization for Opioid Use Disorder - National

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Credit: FAIR Health

NEW YORK, NY—October 14, 2026—Commercially insured patients with diagnoses of opioid use disorder increased 32.7 percent nationally from 2022 to 2025, according to FAIR Health’s Opioid Tracker. In 2022, there were 449 patients with opioid use disorder diagnoses per 100,000 patients, while in 2025, there were 596. This and other findings were reported today when FAIR Health released its annual update of the Opioid Tracker, a free, interactive tool tracking opioid use disorder among commercially insured patients nationally and state by state. A brief released simultaneously offers a user’s guide to the Opioid Tracker.

The Opioid Tracker includes a heat map representing patients with opioid use disorder diagnoses per 100,000 patients receiving medical services in 2025 for each state. Clicking on a state displays an infographic for that state with opioid use disorder data from 2025. The infographic includes the top five procedure code categories by utilization, the top five procedure codes by aggregate allowed amounts,[1] the change in the number of patients with opioid use disorder diagnoses per 100,000 patients from 2022 to 2025, and the distribution of patients by age and gender. There is also a similar infographic for the nation as a whole, along with a second national infographic showing the top five states for opioid use disorder diagnoses, the fastest-growing specialties, the distribution of places of service, and service type (professional versus facility) as a percentage of total allowed amounts. The source of the data is FAIR Health’s repository of commercial health claims.

Among the key findings revealed by the Opioid Tracker:

In 2025, Tennessee had the highest rate of commercially insured patients receiving treatment for opioid use disorder, with 1,551 patients with such a diagnosis per 100,000 patients (compared to 596 patients per 100,000 nationally). It was followed by West Virginia (1,528 patients), Mississippi (1,373 patients), Arkansas (1,320 patients) and Delaware (1,256 patients).

Nationally in 2025, alcohol/substance abuse services and treatments constituted the procedure code category with the highest utilization for opioid use disorder among commercially insured patients, representing 39.0 percent of all claim lines[2] with an opioid use disorder diagnosis.

Nationally in 2025, G2067 (medication-assisted treatment, methadone, weekly bundle) was the procedure code with the highest aggregate allowed amount for opioid use disorder among commercially insured patients, accounting for 9.4 percent of aggregate allowed amounts for that diagnosis. The average allowed amount for this code was $243.

The highest percentage of opioid use disorder diagnoses among commercially insured patients were attributable to patients in the 41 to 50 age group, with 28.1 percent of the total age distribution in 2025 across the nation.

Among commercially insured patients with opioid use disorder diagnoses nationally in 2025, males were 56.1 percent of patients with those diagnoses, while females were 43.9 percent.

The fastest-growing specialty involved in the treatment of opioid use disorder nationally in 2025 was nurse practitioner, which increased 67 percent in percent of claim lines from 2022 to 2025. In second and third positions, respectively, were psychiatric nurse (47 percent) and emergency medicine (44 percent).

For the Opioid Tracker, click here. For the user’s guide to the Opioid Tracker, click here.

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About FAIR Health

FAIR Health’s mission is to supply objective, unbiased information for all stakeholders to improve healthcare quality, access and affordability. It holds the nation’s largest collection of commercial healthcare claims data, which is growing at a rate of more than five billion validated medical services a year. A national Qualified Entity certified by CMS, FAIR Health also receives all claims for individuals enrolled in traditional Medicare Parts A, B and D. As a testament to its reliability and objectivity, FAIR Health’s data products—including pricing benchmarks and custom analytics—are widely used by commercial insurers and self-insurers, providers, hospitals and healthcare systems, government, researchers and more. FAIR Health has been designated an official data source for state health programs, including workers’ compensation and personal injury protection (PIP) programs, and surprise billing laws that protect consumers. FAIR Health’s free consumer website and mobile app, available in English and Spanish, enable consumers to estimate and plan for their healthcare expenses and offer a rich educational platform on health insurance. The website has been honored by the White House Summit on Smart Disclosure, the Agency for Healthcare Research and Quality (AHRQ), URAC, the eHealthcare Leadership Awards, appPicker, Employee Benefit News and Kiplinger’s Personal Finance. FAIR Health is a national, 501(c)(3) nonprofit organization. For more information on FAIR Health, visit fairhealth.org.

 

Contact:

Rachel Kent

Executive Director of Communications and Marketing

FAIR Health

646-396-0795

rkent@fairhealth.org

[1] An allowed amount is the total negotiated, in-network fee paid to the provider under an insurance plan. It includes the amount that the health plan pays and the part the patient pays under the plan’s in-network cost-sharing provisions (e.g., copay or coinsurance if the patient has met the deductible). The aggregate allowed amount for a given procedure is simply the sum of all the allowed amounts for that procedure in the applicable geographic area during the time frame.

[2] A claim line is an individual service or procedure listed on an insurance claim.