Association between Depression and Risk of Colorectal Cancer and Polyps: A Prospective Cohort Study from the Nurses' Health Study II.

Peripheral nerve blocks have become a cornerstone of multimodal peri‐operative pain management across a broad range of surgical procedures. The increase in their use has been driven by the growing availability of ultrasound for guidance, physician familiarity and an emphasis on enhanced recovery protocols []. Moreover, nerve blocks provide site‐specific analgesia, reduce systemic opioid requirements and facilitate earlier postoperative recovery and discharge []. However, the growing use of peripheral nerve blocks has been accompanied by an increased incidence of rebound pain, which is typically described as a sudden and disproportionate increase in pain intensity following the waning of regional block []. Rebound pain is a phenomenon with variable presentation that can emerge within the first 24 h postoperatively, and ranges from mild discomfort in some patients to severe pain, impaired sleep and ambulation and diminished satisfaction with care in others []. It is believed to result from mechanical‐surgical nociceptive input that becomes suddenly unmasked following the resolution of peripheral nerve block‐induced analgesia []. Another proposed mechanism involves tissue injury triggering a localised inflammatory cascade, during which various mediators, such as prostaglandins, bradykinin and cytokines, activate and sensitise peripheral nociceptors at and around the site of injury []. Inadequate management of rebound pain may contribute to increased postoperative opioid consumption, delayed ambulation or unexpected hospital readmission, all of which can undermine the benefits of regional blocks in enhanced recovery pathways []. As surgical teams aim to minimise peri‐operative suffering, rebound pain has become recognised as an important limitation to the otherwise favourable risk–benefit profile of regional analgesia. Several interventions have been explored to mitigate rebound pain, including systemic administration of corticosteroids, N‐methyl‐D‐aspartate (NMDA) receptor antagonists and α‐2 adrenergic agonists, as well as perineural adjuncts. In addition, perineural catheters and pre‐emptive opioid administration before block regression have been proposed as potential prophylactic strategies. Although individual randomised controlled trials have shown promising effects for several of these approaches, comparative effectiveness for these interventions remains poorly understood. Previous studies have been limited to pairwise comparisons between single drugs and placebo or standard care, thus providing insufficient guidance on the relative efficacy of multiple possible approaches.