Evaluation of a refined carprofen-based analgesic regimen for stereotactic surgeries in rats

Carprofen is a commonly used non-steroidal anti-inflammatory analgesic, but data on pharmacokinetics and analgesic efficacy after neurosurgical interventions are limited. This study aimed to evaluate a carprofen-based analgesic regimen for craniotomies by monitoring plasma concentrations and physiological parameters.Sprague-Dawley rats (n=6) underwent subcutaneous transmitter implantation for heart rate and activity monitoring. Intracerebral 6-OHDA injection was conducted, and six weeks later depth electrodes were implanted. Oral carprofen treatment (10 mg/kg/24h) started the day prior to surgeries and was continued for three days. Additionally, lidocaine was applied onto the periost and carprofen was injected once subcutaneously 2h after surgery (5 mg/kg). Plasma concentration was determined 12, 24, and 36h after surgeries, and body weight, water intake, and clinical score values were documented daily.Intake of carprofen-medicated water was increased after transmitter implantation (66.1-88.5%), reduced post 6-OHDA injection (24.6-63.6%), and rather stable post electrode implantation. Carprofen levels were well above the estimated therapeutic threshold (89000nM) at all investigated time points (171867±61109nM transmitter, 252625±87632nM electrodes), apart from 24 and 36h after 6-OHDA injection. Individual rats had increased clinical score values post craniotomies and body weight dropped by 6.8% on d1 post 6-OHDA injection. Heart rate and activity data is currently under evaluation.Intraoperative local anaesthesia in combination with mainly non-invasive oral carprofen treatment starting one day prior to surgery might represent a favorable analgesic regimen for stereotactic surgeries in rats. However, close monitoring of drinking water intake is mandatory to ensure uptake of the target dose.