Rat Experimental Model of Myocardial Ischemia/Reperfusion Injury: An Ethical Approach to Set up the Analgesic Management of Acute Post-Surgical Pain

Abstract

RationaleDuring the past 30 years, myocardial ischemia/reperfusion injury in rodents became one of the most commonly used model in cardiovascular research. Appropriate pain-prevention appears critical since it may influence the outcome and the results obtained with this model. However, there are no proper guidelines for pain management in rats undergoing thoracic surgery. Accordingly, we evaluated three analgesic regimens in cardiac ischemia/reperfusion injury. This study was strongly focused on 3R’s ethic principles, in particular the principle of Reduction.MethodsRats undergoing surgery were treated with pre-surgical tramadol (45 mg/kg intra-peritoneal), or carprofen (5 mg/kg sub-cutaneous), or with pre-surgical administration of carprofen followed by 2 post-surgery tramadol injections (multi-modal group). We assessed behavioral signs of pain and made a subjective evaluation of stress and suffering one and two hours after surgery.ResultsMulti-modal treatment significantly reduced the number of signs of pain compared to carprofen alone at both the first hour (61±42 vs 123±47; p<0.05) and the second hour (43±21 vs 74±24; p<0.05) post-surgery. Tramadol alone appeared as effective as multi-modal treatment during the first hour, but signs of pain significantly increased one hour later (from 66±72 to 151±86, p<0.05). Carprofen alone was more effective at the second hour post-surgery when signs of pain reduced to 74±24 from 113±40 in the first hour (p<0.05). Stress behaviors during the second hour were observed in only 20% of rats in the multimodal group compared to 75% and 86% in the carprofen and tramadol groups, respectively (p<0.05).ConclusionsMulti-modal treatment with carprofen and tramadol was more effective in preventing pain during the second hour after surgery compared with both tramadol or carprofen. Our results suggest that the combination of carprofen and tramadol represent the best therapy to prevent animal pain after myocardial ischemia/reperfusion. We obtained our results accordingly with the ethical principle of Reduction.

Real-time application of the Rat Grimace Scale as a welfare refinement in laboratory rats

“…Somewhat unexpectedly, the multimodal treatment group (buprenorphine and meloxicam) exhibited similar RGS scores to the buprenorphine treatment group at all time points, when it might be expected that a multimodal analgesic approach with a non-steroidal anti-inflammatory agent (NSAID) and opioid would result in lower RGS scores 3 27 28 . There are several interpretations of these findings.…”

Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

“…Different schemes of analgesics have been employed, such as caprofen, buprenorphine and tramadol [81, 446]. However, the selection of analgesics should be considered with caution.…”

A Review of Pain Assessment Methods in Laboratory Rodents

“…40 Assessing animals before and after analgesic administration or comparing animals that received different agents or routes can often reveal whether the analgesic regimen is effective (Figure 8). 22 With this approach, it is important to understand the direction in which the chosen assessment parameter will change if pain is alleviated. For example, for paw withdrawal in response to mechanical pressure, one would expect latency to increase if the animal becomes more comfortable.…”