Comparison of Pain-Like behaviors in two surgical incision animal models in C57BL/6J mice

BACKGROUND: Management of pain post-surgery is crucial for tissue healing in both veterinary and human medicine. Overuse of some analgesics such as opioids may lead to addictions and worsen pain syndromes (opioid-induced hyperalgesia), while underuse of it may affect the welfare of the patient. Therefore, the importance of using surgery models in laboratory animals is increasing, with the goal of improving our understanding of pain neurobiology and developing safer analgesics. METHODS: We compared the widely used plantar incision model with the laparotomy surgery model and measured pain-related behaviors using both spontaneous and evoked responses in female and male C57BL/6J mice. Additionally, we assessed conditioned place preference (CPP) and sucrose preference tests to measure pain-induced motivation for the analgesic ketoprofen and anhedonia-like behavior. RESULTS: Laparotomized mice showed increased abdominal sensitivity while paw-incised mice showed increased paw thermal and mechanical sensitivity up to seven days post-surgery. Laparotomy surgery reduced all spontaneous behaviors in our study however this effect dissipated by 24 h post-laparotomy. On the other hand, paw incision only reduced the percentage of cage hanging in a sex-dependent manner at 6 h post-incision. We also showed that both surgery models increased conditioned place preference for ketoprofen while preference for sucrose was only reduced at 24 h post-laparotomy. Laporatomy, but not paw incision, induced a decrease in body weight at 24 h post-surgery. Neither surgery model affected fluid intake. CONCLUSION: Our results indicate that post-surgery hypersensitivity and behavioral deficits may differ by the incision site. Furthermore, factors associated with the surgery including length of the incision, duration of the anesthesia, and the layers that received stitches may affect subsequent spontaneous behaviors. These findings may help to improve drug development or the choice of the effective analgesic, depending on the surgery type.