Osteotomy models – the current status on pain scoring and management in small rodents

Abstract

Fracture healing is a complex regeneration process which produces new bone tissue without scar formation. However, fracture healing disorders occur in approximately 10% of human patients and cause severe pain and reduced quality of life. Recently, the development of more standardized, sophisticated and commercially available osteosynthesis techniques reflecting clinical approaches has increased the use of small rodents such as rats and mice in bone healing research dramatically. Nevertheless, there is no standard for pain assessment, especially in these species, and consequently limited information regarding the welfare aspects of osteotomy models. Moreover, the selection of analgesics is restricted for osteotomy models since non-steroidal anti-inflammatory drugs (NSAIDs) are known to affect the initial, inflammatory phase of bone healing. Therefore, opioids such as buprenorphine and tramadol are often used. However, dosage data in the literature are varied. Within this review, we clarify the background of osteotomy models, explain the current status and challenges of animal welfare assessment, and provide an example score sheet including model specific parameters. Furthermore, we summarize current refinement options and present a brief outlook on further 3R research.

Spatial Distribution of Macrophages During Callus Formation and Maturation Reveals Close Crosstalk Between Macrophages and Newly Forming Vessels

“…Surgery was performed by two trained veterinarians. For general scoring and humane endpoints, optimized protocols were used which has been summarized in Lang et al (34).…”

Analgesia and mouse strain influence neuromuscular plasticity in inflamed intestine

“…We used tramadol according to standard practice, as it has been used widely in rodents and shown effective in mice and rats on diverse models of pain in recent years, whether arising as neuropathic pain, postsurgical pain, or formalin‐induced pain . There is little similar work in rodent models of intestinal inflammation, where its use has been neglected.…”

“…41 We used tramadol according to standard practice, as it has been used widely in rodents and shown effective in mice and rats on diverse models of pain in recent years, whether arising as neuropathic pain, postsurgical pain, or formalin-induced pain. 17,[42][43][44][45][46][47] There is little similar work in rodent models of intestinal inflammation, where its use has been neglected. However, tramadol at 20 mg kg −1 , as used here and as recommended, 16 was effective against intraperitoneal acetic acid-induced writhing in the mouse and heat-induced tail flick.…”

Limbostomy: Longitudinal Intravital Microendoscopy in Murine Osteotomies

“…Animals were bred in our colony and kept in a conventional specific pathogen‐free barrier facility. Prior to surgery, 14‐week‐old female animals received Buprenorphine (0.03 mg/kg; Temgesic®, Indivior Deutschland GmbH, Mannheim, Germany) s.c. as analgesic, one injection of 0.04% Enrofloxacin (Baytril®, 10 mg/kg body weight Bayer AG, Leverkusen, Germany) , and dexpanthenol‐containing eye ointment (Bepanthen®, Bayer AG, Leverkusen, Germany). Pain was inhibited using Tramadol (0.05 mg/ml; Grünenthal, Aachen, Germany) for 3 days after surgery in drinking water ad libitum.…”