Rebound Pain After Nerve Blocks: The Hidden Pitfall of Regional Anesthesia in Orthopedic Surgery

Regional anesthesia has transformed orthopedic surgery, offering patients powerful pain relief while dramatically reducing their need for opioids. Nerve blocks that numb a shoulder, wrist, or knee can keep patients comfortable for hours after the surgeon has finished. But this clinical success story has a troubling sequel: when the block wears off, many patients are ambushed by a sudden, severe wave of pain that seems to arrive out of nowhere. Anesthesiologists call it rebound pain, and a new narrative review published in Frontiers in Medicine argues that the phenomenon is far more complex—and far more preventable—than a simple side effect of the block wearing off.

The review, led by Alexandra Elena Lazar and colleagues at George Emil Palade University of Medicine, Pharmacy, Science and Technology in Targu Mures, Romania, synthesizes 27 studies identified through a structured PubMed search covering June 2021 to June 2026. The authors conclude that rebound pain is not a single biological event but the product of an interaction between physiological nociceptive processes and modifiable perioperative management factors. In other words, how clinicians manage the transition from regional to systemic analgesia may matter as much as the biology of the block itself.

Defining the phenomenon has proven surprisingly difficult. Most researchers agree that rebound pain involves a clinically relevant increase in pain intensity following the resolution of a previously effective peripheral nerve block, but studies disagree on how to measure it. Some trials use an absolute threshold, such as a Numeric Rating Scale or Visual Analogue Scale score of 7 or higher after the block resolves. Others track the change in pain from the blocked state to the unblocked state, capturing escalations that may never cross a severe-pain cutoff. A composite Modified Rebound Pain Score has been proposed but never externally validated. Because the yardsticks differ, the reported incidence ranges wildly, and direct comparisons between trials are fraught.

The numbers, however, are striking enough to demand attention. After shoulder surgery under a single-shot interscalene block—the highest-risk scenario identified in the review—between roughly one-third and more than 80 percent of patients in control groups experienced rebound pain across randomized trials. Preventive strategies such as intravenous or perineural dexamethasone and multimodal periarticular injections reduced that figure to approximately 20 to 40 percent in several studies. In wrist and hand surgery under supraclavicular block, one trial reported rebound pain in 79 percent of control patients versus 32 percent of those given intravenous dexamethasone. Hip fracture surgery with a liposomal bupivacaine PENG block showed rates of 10 percent versus 43.3 percent with saline. Knee surgery results were less consistent: prolonging block duration alone after unicompartmental knee arthroplasty did not prevent rebound pain and was even associated with higher rebound pain scores in one study.

What explains the phenomenon? The best-supported mechanism is what the authors call the unmasking phenomenon. A peripheral nerve block silences afferent sensory transmission, but it does nothing to stop the surgical injury itself. Inflammation proceeds, peripheral nociceptors become sensitized by prostaglandins, bradykinin, histamine, and cytokines, and nociceptive input continues to build at the surgical site—all while the patient feels nothing. When local anesthetic concentrations decline and neural conduction recovers, the central nervous system is suddenly re-exposed to an inflamed tissue environment with heightened nociceptor excitability. The pain that arrives is not new; it has been accumulating behind a pharmacological curtain.

Central sensitization—the activity-dependent increase in excitability of neurons within central pain pathways—has been proposed as an alternative driver, but the review finds the evidence wanting. The abrupt onset and typically transient course of rebound pain fit poorly with a sustained centrally mediated hyperalgesic state. The authors position central sensitization as a potential amplifying factor rather than the primary mechanism. Preclinical work adds a further wrinkle: in rats, 0.5 percent ropivacaine sciatic nerve block produced transient heat hyperalgesia as mechanical analgesia resolved, raising the possibility that local anesthetics themselves contribute a hyperalgesic component. That modality-specific animal finding cannot establish clinical causation, but the review argues it should not be dismissed.

Beyond biology, the review highlights a concept it calls the transitional analgesic gap: the interval between loss of regional analgesia and the establishment of effective systemic pain control. This gap is shaped by block duration, the postoperative pain trajectory, the timing of rescue analgesia, and patient expectations—and it is especially dangerous when block resolution occurs after discharge, when no clinician is present to intervene. The gap is a contributor to, not a synonym for, rebound pain, but it is the piece of the puzzle that clinicians can most directly manipulate.

Who is most at risk? The principal multivariable evidence comes from a cohort study by Barry and colleagues, which found that surgery involving bone rather than soft tissue, absence of perioperative intravenous dexamethasone, younger age, and female sex were independently associated with rebound pain. A randomized trial by Touil and colleagues identified severe preoperative pain and high pain catastrophizing as secondary predictive factors, though these exploratory associations require confirmation. The review is careful to note that surgical procedure should be considered a risk marker rather than an independently established causal factor, since comparisons across procedures are confounded by block technique, analgesic protocols, and outcome definitions.

On prevention, the picture is encouraging but uneven. Scheduled multimodal analgesia—acetaminophen, NSAIDs or COX-2 inhibitors, and rescue opioids when indicated—should be initiated while the block is still working, rather than waiting for pain to return. Continuous peripheral nerve catheters and prolonged regional techniques have generally attenuated rebound pain, with continuous infraclavicular blockade reducing early rebound pain after distal radius fixation. Dexamethasone is the most extensively investigated adjuvant, and meta-analytic evidence supports an overall reduction in rebound-pain incidence after single-injection blocks, though individual trials have reported no benefit or even increased incidence despite prolonged block duration. Notably, opioid-based prevention failed: pre-emptive oral hydromorphone did not reduce rebound pain severity, pain trajectory, or opioid consumption after shoulder arthroscopy. A single anti-hyperalgesic dose of intravenous ketamine likewise failed to reduce severe rebound pain in ambulatory upper-limb surgery, and intravenous esketamine showed no benefit after interscalene block, though it did help after thoracic paravertebral block.

The review’s practical message is that no single intervention is uniformly effective, and management should remain procedure-specific and individualized. For hospitalized patients, the transition can be supervised with scheduled multimodal analgesia, timely rescue medication, and regular pain assessment during block resolution. For ambulatory patients, who frequently lose their blocks at home, clear verbal and written instructions about the expected duration of the block, the anticipated return of sensation, and the importance of starting scheduled analgesics before the block wears off are essential. The authors call for a consensus definition developed through formal methods such as a Delphi process, a core outcome set combining pain intensity, analgesic consumption, sleep quality, and functional recovery, and adequately powered procedure-specific trials with standardized background analgesia. Until then, rebound pain remains a reminder that the end of a nerve block is not the end of the anesthetic plan—it is the moment the plan matters most.

Subject of Research: Rebound pain following peripheral nerve block resolution in orthopedic surgery

Article Title: Rebound pain after regional anesthesia in orthopedic surgery: current evidence and clinical implications – a narrative review

Article References: Lazar, A. E., Frandeș, O., Gherghinescu, M. C., & Azamfirei, L. (2026). Rebound pain after regional anesthesia in orthopedic surgery: current evidence and clinical implications – a narrative review. Frontiers in Medicine, 13, Article 1930868. https://doi.org/10.3389/fmed.2026.1930868

Image Credits: AI Generated

DOI: 10.3389/fmed.2026.1930868

Keywords: rebound pain, regional anesthesia, peripheral nerve block, orthopedic surgery, multimodal analgesia, dexamethasone, central sensitization, transitional analgesic gap, postoperative pain, anesthesiology, opioid sparing, nerve block resolution