Behavioral assessment of tramadol and meloxicam effects on postoperative pain in a rat craniotomy model (2025)

Alemán-Laporte, J., Alvarado, G., Pellagio, N. B. et al.

Abstract

Stereotaxic surgery is a common procedure in neuroscience, yet effective analgesic protocols require further study and refinement to optimize the analgesia used in invasive procedures and to improve animal welfare. This study evaluated the effects of tramadol and meloxicam, alone or combined, on pain management following craniotomy in rats. Forty Wistar-Han rats were divided into 5 groups: saline + anesthesia (SAL+ANE), saline + surgery (SAL+SUR), tramadol + surgery (TRA+SUR), meloxicam + surgery (MEL+SUR), and tramadol/meloxicam + surgery (TRA/MEL+SUR). Treatments (saline, 0.2 mL; tramadol, 17.8 mg/kg; meloxicam, 1.5 mg/kg) were administered subcutaneously every 12 h for 72 h. The animals underwent anesthesia or surgery 30 min after the first injection. Postoperative assessments included open field testing, a grooming transfer test, nesting behavior, body weight, and food/water intake. Surgery induced behavioral changes occured within 48 h. SAL+SUR and MEL+SUR groups showed increased locomotion and rearing, while SAL+SUR, TRA+SUR, and TRA/MEL+SUR groups had reduced grooming. TRA/MEL+SUR and SAL+SUR groups had the lowest grooming transfer test scores, and TRA/MEL+SUR rats displayed reduced nesting behavior. Craniotomy caused mild pain lasting at least 48 h. Although no optimal analgesic was identified, providing analgesia and refining surgical techniques are essential to ensure animal welfare.