Nerve stimulation could reduce postsurgical pain and opioid use
35th Journal Symposium: Changing paradigm may usher in a new direction in surgical recovery.
There’s a new way of thinking in the management of acute perioperative pain, one that moves away from opioid-centric protocols and toward individualized, multimodal strategies supported by real-world population data. Two complementary trends driving this evolution will be presented at the Sunday session, “35th Journal Symposium: Advancing Acute Perioperative Pain Management: Precision, Populations, and Innovative Interventions.”
Session speaker Justin James said one trend is the emergence of regional anesthesia as a cornerstone of Enhanced Recovery After Surgery (ERAS) protocols. The second trend relates to federated electronic health record networks, such as TriNetX, which now enables researchers to study tens of thousands of patients across hundreds of health systems simultaneously, capturing the heterogeneity of real-world practice that trials cannot. James, an MD candidate at Penn State College of Medicine in Hershey, Pennsylvania, who is applying for anesthesiology residency, will detail the results of a recent Penn State study to further address the topic.
“Our study’s findings have direct implications for health equity,” he said. “Real-world database studies like ours are uniquely positioned to identify disparities in the delivery of evidence-based analgesic interventions across racial, ethnic, and socioeconomic groups – disparities that randomized trials, which are conducted in selected populations at academic centers, systematically miss.”
The large population-based study, conducted in collaboration with Sanjib Adhikary, MD, MBBS, Chief of the Division of Regional Anesthesia and Acute Pain Management Services at Penn State Health, found that perioperatively adding ketamine to regional anesthesia may be associated with lower rates of chronic pain following surgery. The study also highlighted the need for closer monitoring of patients at higher psychiatric- and opioid-related risk.
Using the TriNetX Global Collaborative Network, which included data from 172 healthcare organizations and approximately 300 million patients, researchers analyzed adults who underwent surgery and received a regional anesthesia procedure. After propensity score matching, the study compared two groups of 26,200 patients each: those who received injectable ketamine around the time of surgery and those who did not.
According to James, the study found that patients who received ketamine in combination with regional anesthesia experienced lower rates of chronic pain several months after surgery. At 180 days, chronic pain was reported in 9% of patients receiving ketamine compared with 12.7% of controls. At 365 days, rates were 13.6% versus 16.5%, respectively. The ketamine group also experienced fewer pain-related healthcare encounters during the first 30 days after surgery.
“These associations are hypothesis-generating and support prospective study of whether perioperative ketamine can complement regional anesthesia within multimodal, opioid-sparing care,” he said.
James did offer a word of caution. The study also identified higher rates of new depression and opioid use disorder diagnoses among patients who received ketamine. At one year, 4.1% of ketamine recipients had a new depression diagnosis compared with 3.2% of controls, while new opioid use disorder diagnoses occurred in 0.7% of ketamine patients versus 0.4% of controls.
James said the findings should not be interpreted as proof that ketamine caused the increases. Instead, researchers believe the results likely reflect "confounding by indication," meaning clinicians may be more likely to administer ketamine to patients who already have greater pain burdens, opioid tolerance, or psychiatric vulnerabilities.
“The findings also underscore the importance of psychological screening and structured postoperative follow-up for patients considered at elevated risk,” he said.
In another study, to be presented by speaker Brian Ilfeld, MD, there is new evidence that percutaneous peripheral nerve stimulation (PNS), a minimally invasive form of neuromodulation, may dramatically reduce acute postoperative pain, decrease opioid consumption, and lower the risk of chronic pain following surgery. Dr. Ilfeld is a Professor of Anesthesiology at the University of California, San Diego, School of Medicine.
Current alternatives to opioids, including local anesthetic injections and nerve blocks, can be effective but often come with limitations, he said. Single-injection nerve blocks typically last less than 24 hours, while continuous infusions are generally used for only a few days, despite postoperative pain often lasting weeks. Additionally, Dr. Ilfeld said nerve blocks can impair sensation, balance, and motor function, potentially affecting rehabilitation and increasing fall risk.
“Percutaneous peripheral nerve stimulation has been FDA-cleared and used for decades in the United States, but usually for treating chronic pain, or pain that goes on for months and years, and we are not sure what causes it,” Dr. Ilfeld said. “However, our pragmatic, multicenter, randomized, controlled clinical trial sheds new light on the discussion.”
In Dr. Ilfeld’s study, researchers analyzed 250 patients undergoing painful shoulder or foot and ankle surgeries. Participants were assigned to receive either active nerve stimulation or a sham treatment for 14 days following surgery. During the first week of recovery, patients receiving active stimulation experienced a 59% reduction in pain compared with the control group. At the same time, opioid consumption fell by 78% among those receiving the therapy.
According to Dr. Ilfeld, patients treated with active stimulation continued to experience lower average and worst pain scores throughout the two-week treatment period. They also reported less physical and emotional interference from pain, suggesting broader improvements in postoperative recovery and quality of life.
Perhaps most notably, the therapy showed promise in preventing the transition from acute to chronic pain – a persistent challenge in postoperative care, he said. Four months after surgery, chronic pain rates dropped by 44% among patients who received active stimulation. After one year, the incidence of chronic pain remained significantly reduced, with rates 56% lower than those observed in the control group. Dr. Ilfeld said there were no major adverse events associated with the treatment.
“The sustained reduction in chronic pain observed in this trial suggests that aggressive, early neuromodulation may fundamentally alter the physiological trajectory of surgical recovery,” Dr. Ilfeld said. “Well-powered multicenter trials are now required to confirm the efficacy of peripheral nerve stimulation for preventing the transition from acute to chronic pain across various surgical specialties.”
Dr. Ilfeld said the results will also be helpful to evaluate peripheral nerve stimulation in populations that have an especially high risk of transitioning to persistent pain – specifically “those with preexisting pain syndromes, high levels of preoperative anxiety, or opioid tolerance.”
The full panel will be led by Chad Brummett, MD, and Kristin Schreiber, MD, PhD, and features presentations from Mark Bicket, MD, PhD, FASA, Jennifer Rabbitts, MD, and Beth Darnall, PhD.
