Postoperative pain remains highly prevalent and inadequately managed in a significant proportion of surgical patients, often leading to delayed recovery, increased opioid consumption, and potential progression to chronic pain. While perioperative systemic dexamethasone is used for its anti-inflammatory and opioid-sparing effects, its efficacy is inconsistent, and concerns regarding systemic side effects persist. Dexamethasone palmitate, a novel lipophilic prodrug formulated as nanoparticle emulsion, leverages the enhanced permeability and retention effect to target inflammatory sites selectively, potentially offering superior anti-inflammatory and analgesic efficacy with reduced systemic exposure. This trial aims to evaluate whether preoperative intravenous dexamethasone palmitate is more effective than conventional dexamethasone in preventing moderate-to-severe postoperative pain.

Inclusion Criteria:

1. Age 18-65 years.
2. Scheduled for a range of surgeries under general anesthesia, including both minimally invasive procedures (such as video-assisted thoracoscopic surgery and laparoscopy) and open surgeries (such as thoracotomy, laparotomy, spinal surgery, total joint replacement, and mastectomy).
3. Capacity to comprehend the study procedures and assessment scales, and communicate effectively with research staff.

4）Classified as American Society of Anesthesiologists (ASA) physical status I, II, or III.

5) Willingness to participate voluntarily and provide written informed consent.

Exclusion Criteria:

1. Known hypersensitivity to dexamethasone or its excipients.
2. Systemic glucocorticoid therapy within 3 months prior to enrolment.
3. History of severe cardiovascular disease, hepatic or renal failure, or systemic rheumatic disease (e.g., rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus).
4. Coexisting chronic pain at enrolment.
5. Uncontrolled diabetes mellitus or active systemic infection.
6. Use of any systemic or topical analgesics within 48 hours prior to surgery.
7. Significant cognitive impairment or severe psychiatric disorder.
8. Pregnancy or lactation.

All personal identifiers will be stored securely by the principal investigator, separate from the pseudonymized study data. Access is restricted to the research team, and all published findings will be based on anonymized data aggregates.

1. Due to the visually distinct formulations-an opaque, white suspension (dexamethasone palmitate) versus a transparent solution (conventional dexamethasone)-blinding of the anaesthesiologists will not be feasible.
2. This unavoidable lack of blinding at the point of administration made it highly probable that the attending surgeons and the participants themselves could become aware of the treatment group assignment.
3. All postoperative follow-up evaluations will be conducted by outcome assessors who remain fully blinded to group allocation throughout the study.
4. The biostatistician will be blinded and will have no access to interim data until database lock.