Analgesic effects of intravenous morphine, fentanyl, sufentanil, and ketamine in a novel rat model of extremity trauma
Abstract
The goal of the current study was to establish a rat model of extremity trauma (ET)for prehospital pain research and validate it using different pain behaviors and analgesics applied via intravenous (IV) injection. Male Sprague Dawley rats (11–13 wk) were briefly anesthetized using isoflurane and ET was induced via clamping there trofemoral tissue groups for 30 sec using an L‐shaped hemostat, followed by closed fibula fracture using a 15‐gauge needle. Rats regained consciousness within 5 minutes after ET. Pain responses to thermal hyperalgesia (paw withdrawal latency of injured hindlimb, PWL), mechanical allodynia (paw withdrawal pressure of injured hindlimb, PWP), and weight bearing (WB) were determined prior to and 90 minutes after ET. Morphine (2 mg/kg), fentanyl (10 μg/kg), sufentanil (1 μg/kg), ketamine (5 mg/kg), or vehicle(saline) was then administered via IV injection, followed by PWL, PWP, WB, and TF assessments at 10, 40, 80, and 120 minutes after analgesic injection. Ninety minutes after ET, the PWL, PWP, and WB were significantly decreased by 61 ± 4%, 64 ± 8%, and 65 ± 4%, respectively, compared to baseline values. These pain behaviors were steadily maintained throughout the 3–4 hours of observation. Compared with the saline‐treated group, opioid analgesics significantly increased PWL during more than 80 minutes, with sufentanil exhibiting the highest analgesic effect. An increase in PWL was only observed at 10 minutes after ketamine injection. PWP was transiently increased with opioid analgesics for 10 to 40 minutes but was not changed with ketamine. WB was improved with opioid analgesics for atleast 2 hours but only for up to 80 minutes after ketamine injection. The ET model includes long bone fracture and soft tissue injury but no fixation surgery, mimicking prehospital extremity trauma, and produces acute, steady, and reproducible trauma‐related pain behaviors. Our model is clinically relevant regarding the pain behaviors and established responses to common analgesics.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2018
- Source ID
- 10.1096/fasebj.2018.32.1_supplement.877.3
Entities
People
- Carmen Hinojosa‐laborde
- Harold G. Klemcke
- Kathy Ryan
- Lusha Xiang
Organizations
- United States Army
- United States Army Institute of Surgical Research