Rabbits (Oryctolagus cuniculus) as a Model System for Longitudinal Experimental Opioid Treatments: Implications for Orthopedic and Biomedical Research

Due to the high prevalence of opioid prescription following orthopedic procedures, there is a growing need to establish an animal model system to evaluate the effects of opioids on bone remodeling. Rabbits have been employed as model organisms in orthopedic research as they exhibit well-defined cortical bone remodeling similar to humans. Existing research in rabbits has been limited to modes of opioid administration that are short-acting and require repeated application. Here, we present data from a proof-of-principle longitudinal study employing two opioid analgesic administration routes (subcutaneous injection and transdermal patch) to evaluate the efficacy of studying chronic opioid exposure in a rabbit model. Skeletally mature male New Zealand White rabbits (Oryctolagus cuniculus) were divided into three groups of seven animals: morphine, fentanyl, and control. Experimental treatments were conducted for eight weeks. Preparation of the skin at the fentanyl patch site and subsequent patch removal presented experimental difficulties including consistent skin erythema. Though noninvasive, the patches further caused acute stress in fentanyl animals. We conclude that though transdermal fentanyl patches may be preferred in an acute clinical setting, this method is not feasible as a means of long-term pain relief or opioid delivery in a laboratory context.