Severe Pain and Low Opioid Doses Predict Who Responds Best to Nerve Blocks for Cancer Pain

For millions of people living with cancer, pain is not a side effect of treatment but a constant companion of the disease itself. Roughly 44.5 percent of cancer patients experience pain, and nearly a third suffer moderate-to-severe pain, a burden that grows heavier as the disease advances. Now, a large retrospective study from Seoul National University Bundang Hospital offers a strikingly practical answer to one of palliative medicine’s most stubborn questions: which hospitalized cancer patients are most likely to benefit, and benefit quickly, from an interventional pain procedure? The findings, published in Supportive Care in Cancer, suggest that the answer lies in two numbers already recorded in every patient’s chart: how much pain they are in, and how much opioid they are taking.

The research team, led by Joon Hee Lee and Eun Joo Choi of the Department of Anesthesiology and Pain Medicine, analyzed the records of 349 hospitalized patients who underwent their first inpatient interventional pain procedure, or IPP, between January 2022 and December 2023. These procedures, which include epidural steroid injections, nerve blocks, and neurolytic techniques such as celiac plexus neurolysis, have traditionally been viewed as a last resort, deployed only after the World Health Organization’s famous analgesic ladder of oral medications has failed. But a growing body of evidence has been pushing clinicians toward a paradigm shift, one in which these targeted interventions are deployed earlier, alongside drugs rather than after them, to interrupt pain before it becomes entrenched.

To measure whether a procedure worked, the researchers did not rely on a single pain score. Instead, they built a composite definition of early analgesic response that tracked two variables simultaneously over the 48 hours surrounding the procedure: the patient’s mean pain rating on the 0-to-10 Numerical Rating Scale, and their morphine equivalent daily dose, or MEDD, calculated according to the 2022 CDC Clinical Practice Guideline for Prescribing Opioids. A complete response meant pain had vanished entirely without any rise in opioid need. A partial response required either a drop of at least two NRS points without increased opioids, or a reduction of at least 25 percent in opioid dose without worsening pain. Patients whose pain scores climbed by two points or whose opioid needs surged by a quarter were classified as having pain progression, while everyone else fell into the indeterminate category.

The results were sobering at first glance. Only 25.5 percent of patients, 89 of the 349, met the strict criteria for an overall response, and just two of those achieved complete pain elimination. The remaining 260 patients were classified as non-responders, the vast majority of them in the indeterminate category. Yet the picture is more nuanced than the headline number suggests. Even among non-responders, the overall distribution of pain scores shifted significantly downward after the procedures, without a corresponding rise in opioid consumption. In other words, many patients who failed to cross the formal response threshold still derived some measurable relief. And the safety profile was remarkable: across all 349 procedures, there was a single complication, one pneumothorax requiring intervention, an incidence of just 0.3 percent.

The predictive modeling produced the study’s most clinically actionable insight. Using multivariable logistic regression, the team found that higher baseline pain intensity more than doubled the odds of an early response, with an odds ratio of 2.13 for each increment on the NRS. Conversely, every additional 10 milligrams of baseline morphine equivalent daily dose reduced the odds of response by about 5 percent, with an odds ratio of 0.95. Patients in severe pain who had not yet been escalated to high-dose opioids were, in essence, the sweet spot. One specific procedure also stood out: celiac plexus or splanchnic nerve neurolysis, which targets visceral pain from upper abdominal malignancies, was independently associated with better responses compared with epidural steroid injection, achieving a 42.3 percent response rate in the 26 patients who received it.

Why would heavy opioid exposure blunt the effect of a nerve block? The authors point to two pharmacological mechanisms. The first is cross-tolerance between opioids and local anesthetics, a phenomenon documented in studies of chronic opioid users, in whom spinal anesthesia with bupivacaine and lidocaine wears off faster and works less effectively. The second is opioid-induced hyperalgesia, a paradoxical state in which prolonged high-dose opioid exposure actually sensitizes the nervous system to pain. Both mechanisms would dampen the analgesic payoff of an otherwise well-placed injection. Combined with evidence that shorter pain duration improves outcomes, the findings sketch a therapeutic window defined on two axes: chronologically, before chronic neuroplastic changes take hold, and pharmacologically, before opioid escalation rewires the patient’s pain processing.

The study also ventured into more speculative territory: whether early pain relief predicts survival. In the crude analysis, overall responders lived a median of 203 days after referral, compared with 98 days for non-responders, and their estimated one-year survival rate was 39.0 percent versus 25.0 percent, a difference that reached statistical significance. The researchers handled a thorny methodological problem with unusual care. Among the 349 patients, 186 lacked complete one-year follow-up, and 133 of those had transitioned to hospice care. Because hospice transition in South Korea typically signals impending death in terminal cancer, the team counted those patients as deaths on the date of transition, a deliberate strategy to mitigate informative censoring bias.

But the survival signal dissolved under scrutiny. In sensitivity analyses that treated lost-to-follow-up patients under best-case and worst-case assumptions, the survival advantage flickered, remaining significant only in the worst-case scenario. And in the multivariable Cox proportional hazards model, early analgesic response lost its independent association with one-year mortality entirely, with an adjusted hazard ratio of 1.26 for non-responders versus responders and a P value of 0.176. What did predict death were the brutal fundamentals of advanced cancer: the presence of metastasis tripled the hazard, higher baseline opioid dose and older age each independently increased it. The authors are appropriately cautious, framing early analgesic response as an exploratory prognostic indicator that warrants prospective validation rather than a proven survival marker.

The cohort itself tells a story about the modern landscape of cancer pain. Lung cancer accounted for 28.1 percent of patients, pancreatic cancer for 17.3 percent, and colorectal cancer for 9.2 percent, malignancies all notorious for severe pain burdens. Metastatic disease was present in over 93 percent of the cohort, and nearly 62 percent had bone metastases, which explains why epidural steroid injection was the most common procedure at 55.6 percent of cases, and why lower back and pelvic pain with or without radiating symptoms was the most frequently reported pain location. These are patients whose disease had already spread, whose performance status was often declining, and whose options were narrowing, precisely the population in whom a safe, rapid, drug-sparing intervention could matter most.

The study’s limitations are real and the authors enumerate them candidly. The retrospective design invites selection bias and residual confounding. Mean daily NRS scores can mask breakthrough pain episodes. The Eastern Cooperative Oncology Group performance status, one of the strongest known prognostic factors in oncology, was missing for enough patients that it had to be excluded from the final models, a gap that could have distorted both the response and survival analyses. And because the study focused on the immediate 48-hour window, long-term analgesic durability remains unknown. Still, the core message survives these caveats intact: interventional pain procedures are safe enough, and effective enough in the right patients, to justify moving them up the treatment timeline. For clinicians, the practical takeaway is to refer patients for procedural evaluation while their pain is severe but before their opioid requirements have climbed, rather than waiting for the pharmacological ladder to run out of rungs. For patients facing the cruelest symptom of a cruel disease, that shift in timing could mean more days lived comfortably, whatever the total number of days turns out to be.

Subject of Research: Predictors of early analgesic response to interventional pain procedures in hospitalized patients with cancer-related pain and their exploratory association with one-year survival

Article Title: Early analgesic response to interventional pain procedures in hospitalized patients with cancer-related pain: clinical predictors and exploratory survival analysis

Article References: Lee, J. H., Yoon, J., Min, B., Chang, M., Nahm, F. S., Lee, P. B., & Choi, E. J. (2026). Early analgesic response to interventional pain procedures in hospitalized patients with cancer-related pain: clinical predictors and exploratory survival analysis. Supportive Care in Cancer, 34(10), Article 945. https://doi.org/10.1007/s00520-026-11004-2

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11004-2

Keywords: cancer-related pain, interventional pain procedures, opioid dose, numerical rating scale, morphine equivalent daily dose, epidural steroid injection, celiac plexus neurolysis, palliative care, survival analysis, pain management, metastasis, therapeutic window