Definitional and interpretive challenges in rebound pain prevention

We read with interest the network meta-analysis by Singh et al. on prophylactic interventions for rebound pain after peripheral nerve block [1]. Their analysis of 24 randomised, controlled trials involving 2130 patients addresses an important clinical question, but some features of the analysis warrant caution when interpreting the reported treatment hierarchy. First, the primary outcome was the incidence of rebound pain as defined by the authors of each study [1]. Restricting inclusion to trials that reported rebound pain explicitly improves terminological consistency, but not necessarily outcome comparability. Current literature supports a broadly shared clinical description of rebound pain after peripheral nerve block, but not a single standardised definition. Generally, the reviews describe it as a transient yet marked exacerbation of acute postoperative pain occurring as sensory blockade resolves, often characterised by abrupt onset and severe intensity [2, 3]. However, individual studies have operationalised this construct differently. Some use absolute pain score thresholds after block resolution; others define it as a transition from well-controlled pain to severe pain within a prespecified time window; and some incorporate related features such as rescue analgesic requirement or other indicators of pain escalation [2-4]. Rebound pain therefore appears to have a consistent phenomenological core but a heterogeneous operational definition across studies. In this context, use of the same term does not necessarily indicate that equivalent outcomes have been measured. As Jen and Uppal also note, definitions vary in their thresholds, reference points and observation windows [5]. The pooled primary outcome may therefore reflect non-equivalent pain constructs rather than a single standardised outcome. If so, apparent differences between interventions may partly arise from variation in endpoint definition, not treatment effect alone. Second, this limitation carries through to treatment ranking. Singh et al. found that intravenous dexamethasone had the highest probability of reducing the incidence of rebound pain, with a surface under the cumulative ranking curve value of 0.91 [1]. However, for the primary outcome, only one trial directly compared active interventions, and most active comparisons were, therefore, driven by indirect evidence [1]. As the accompanying editorial also highlights, these estimates were often imprecise, with credible intervals crossing no effect [5]. In this setting, ranking alone is a thin basis for claiming superiority. A high ranking is more convincing when supported by precise estimates and direct comparisons, neither of which were consistently available across the network. Intravenous dexamethasone may, therefore, be the best supported option at present, but not yet a definitively superior strategy. Third, several interventions considered beneficial against rebound pain, including dexamethasone and other adjuvant strategies, may also prolong block duration. In such cases, an observed reduction in the incidence of rebound pain does not clearly distinguish true prevention of the phenomenon from temporal displacement of pain emergence. If pain exacerbation is delayed beyond the main observation window, the intervention may appear protective while primarily altering timing rather than reducing the overall postoperative pain burden. This distinction matters clinically, because postponing severe pain is not necessarily equivalent to preventing it. Future studies may therefore benefit from a more event-based definition of rebound pain, anchored to block resolution rather than to a fixed postoperative time window. A definition centred on a clinically meaningful short-interval increase in pain score, for example, ≥3 points on a numerical rating scale, may better capture the dynamic nature of rebound pain, particularly when adjuvants or long-acting local anaesthetic drugs alter block duration. These observations do not detract from the value of the study by Singh et al. Rather, they highlight what the field now needs most: a standardised definition of rebound pain; adequately powered head-to-head trials; and more complete reporting of patient-centred and safety outcomes. Until then, the current evidence supports intravenous dexamethasone as a reasonable default option, but does not establish a definitive hierarchy among active interventions.