Does the Perioperative Administration of Dexamethasone Increase the Incidence of Chronic Postmastectomy Pain? A Double-blind Randomized Controlled Trial

Chronic post-surgical pain is a common complication following mastectomy and represents a significant source of long-term morbidity. Pain that persists beyond the expected period of tissue healing can interfere with physical functioning, psychological well-being, and quality of life. Despite advances in surgical and anesthetic techniques, the mechanisms contributing to chronic postmastectomy pain remain incompletely understood.

Dexamethasone is a corticosteroid routinely administered in the perioperative setting for the prevention of postoperative nausea and vomiting. In addition to its antiemetic properties, dexamethasone has potent anti-inflammatory and immunomodulatory effects that may influence tissue healing and pain processing pathways. Given its widespread use during surgery, understanding its potential impact on long-term pain outcomes is clinically relevant.

Clinical observational studies examining the association between perioperative dexamethasone administration and chronic postmastectomy pain have not demonstrated a clear or consistent relationship. However, by design, observational studies cannot establish causality or definitively exclude a potential effect of perioperative dexamethasone on the development of chronic post-surgical pain.

In contrast, preclinical studies using animal models of post-surgical pain have shown that perioperative exposure to dexamethasone may be associated with increased postoperative pain sensitivity and hyperalgesia. These findings suggest a potential biological mechanism through which perioperative corticosteroid administration could influence long-term pain outcomes, although their relevance to human surgical populations remains uncertain.

To date, no randomized controlled trials have directly evaluated whether perioperative dexamethasone administration affects the incidence of chronic postmastectomy pain in humans. Given the routine use of dexamethasone in perioperative care, the absence of definitive clinical evidence, and the presence of preclinical signals suggesting a possible effect on pain sensitization, a randomized, double-blind, placebo-controlled trial is warranted.

This study focuses on adult patients undergoing mastectomy, a population with a well-established risk of chronic post-surgical pain. Chronic pain will be assessed three months after surgery, a commonly accepted time point for distinguishing chronic post-surgical pain from normal postoperative recovery. The proposed study design aims to minimize bias and generate high-quality evidence to inform perioperative medication practices.