Influence of Pain and Analgesia on Orthopedic and Wound-healing Models in Rats and Mice

Huss, Monika K; Felt, Stephen A.; Pacharinsak, Cholawat

doi:10.30802/aalas-cm-19-000013

Cited by 37 publications

(27 citation statements)

References 126 publications

(140 reference statements)

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“…These findings are in contrast to studies in animal models assessing bone healing in the presence of bupivacaine. Fourteen and thirty-five days after hematoma infiltration with 0.25% bupivacaine following a closed diaphysis fracture in rat femora, no difference in callus composition, bone tensile strength, or histological appearance was observed between bupivacaine-treated and control groups ( 68 , 69 ). Similar results were reported in dogs for 0.5% bupivacaine infiltration ( 70 ).…”

Section: Effects Of Bupivacaine On Bone Repair/regenerationmentioning

confidence: 90%

Comparison of in vitro and in vivo Toxicity of Bupivacaine in Musculoskeletal Applications

et al. 2021

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The recent societal debate on opioid use in treating postoperative pain has sparked the development of long-acting, opioid-free analgesic alternatives, often using the amino-amide local anesthetic bupivacaine as active pharmaceutical ingredient. A potential application is musculoskeletal surgeries, as these interventions rank amongst the most painful overall. Current literature showed that bupivacaine induced dose-dependent myo-, chondro-, and neurotoxicity, as well as delayed osteogenesis and disturbed wound healing in vitro. These observations did not translate to animal and clinical research, where toxic phenomena were seldom reported. An exception was bupivacaine-induced chondrotoxicity, which can mainly occur during continuous joint infusion. To decrease opioid consumption and provide sustained pain relief following musculoskeletal surgery, new strategies incorporating high concentrations of bupivacaine in drug delivery carriers are currently being developed. Local toxicity of these high concentrations is an area of further research. This review appraises relevant in vitro, animal and clinical studies on musculoskeletal local toxicity of bupivacaine.

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Section: Effects Of Bupivacaine On Bone Repair/regenerationmentioning

confidence: 90%

Comparison of in vitro and in vivo Toxicity of Bupivacaine in Musculoskeletal Applications

et al. 2021

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“… 79 Ketamine is a potent analgesic at low doses, possibly mediated, in part, through opiate receptor binding. 80 Ketamine has a short half-life in mice of 13 minutes following IP injection. 81 Xylazine, an alpha-2 adrenergic agonist, produces both sedation and analgesic effects.…”

Section: Anesthetic Depthmentioning

confidence: 99%

Mouse Anesthesia: The Art and Science

et al. 2021

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There is an art and science to performing mouse anesthesia, which is a significant component to animal research. Frequently, anesthesia is one vital step of many over the course of a research project spanning weeks, months, or beyond. It is critical to perform anesthesia according to the approved research protocol using appropriately handled and administered pharmaceutical-grade compounds whenever possible. Sufficient documentation of the anesthetic event and procedure should also be performed to meet the legal, ethical, and research reproducibility obligations. However, this regulatory and documentation process may lead to the use of a few possibly oversimplified anesthetic protocols used for mouse procedures and anesthesia. Although a frequently used anesthetic protocol may work perfectly for each mouse anesthetized, sometimes unexpected complications will arise, and quick adjustments to the anesthetic depth and support provided will be required. As an old saying goes, anesthesia is 99% boredom and 1% sheer terror. The purpose of this review article is to discuss the science of mouse anesthesia together with the art of applying these anesthetic techniques to provide readers with the knowledge needed for successful anesthetic procedures. The authors include experiences in mouse inhalant and injectable anesthesia, peri-anesthetic monitoring, specific procedures, and treating common complications. This article utilizes key points for easy access of important messages and authors’ recommendation based on the authors’ clinical experiences.

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“…To do this, we isolated observations directly to the injury by withholding all analgesics that are known to interfere with gait analysis 18 and bone remodeling. 19,20 Then, we used marker-less deep learning software, DeepLabCut, 21 to track animal movement and performed comprehensive kinematic analyses to better understand the longitudinal changes in knee kinematic profiles. We then investigated subchondral bone architecture via micro computed tomography (μCT) to determine the association between hallmark measures of joint kinematics and PTOA after ACL injury.…”

mentioning

confidence: 99%

Relationship between altered knee kinematics and subchondral bone remodeling in a clinically translational model of ACL injury

White

Brancati

Lepley

2020

Journal Orthopaedic Research

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Abnormal joint kinematics are commonly reported in the acute and chronic stages of recovery after anterior cruciate ligament (ACL) injury and have long been mechanistically implicated as a primary driver in the development of posttraumatic osteoarthritis (PTOA). Though strongly theorized, it is unclear to what extent biomechanical adaptations after ACL injury culminate in the development of PTOA, as data that directly connects these factors does not exist. Using a preclinical, noninvasive ACL injury rodent model, our objective was to explore the direct effect of an isolated ACL injury on joint kinematics and the pathogenetic mechanisms involved in the development of PTOA. A total of 32, 16-week-old Long-Evans rats were exposed to a noninvasive ACL injury. Marker-less deep learning software (DeepLabCut) was used to track animal movement for sagittal-plane kinematic analyses and micro computed tomography was used to evaluate subchondral bone architecture at days 7, 14, 28, and 56 following injury. There was a significant decrease in peak knee flexion during walking (p < .05), which had a moderate-to-strong negative correlation (r = −.59 to −.71; p < .001) with subchondral bone plate porosity in all load bearing regions of the femur and tibia. Additional comprehensive analyses of knee flexion profiles revealed dramatic alterations throughout the step cycle. This occurred alongside considerable loss of epiphyseal trabecular bone and substantial changes in anatomical orientation.Knee flexion angle and subchondral bone microarchitecture are severely impacted after ACL injury. Reductions in peak knee flexion angle after ACL injury are directly associated with subchondral bone plate remodeling.

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Influence of Pain and Analgesia on Orthopedic and Wound-healing Models in Rats and Mice

Cited by 37 publications

References 126 publications

Comparison of in vitro and in vivo Toxicity of Bupivacaine in Musculoskeletal Applications

Comparison of in vitro and in vivo Toxicity of Bupivacaine in Musculoskeletal Applications

Mouse Anesthesia: The Art and Science

Relationship between altered knee kinematics and subchondral bone remodeling in a clinically translational model of ACL injury

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