Modeling Complex Orthopedic Trauma in Rodents: Bone, Muscle and Nerve Injury and Healing

Abstract

Orthopedic injury can occur from a variety of causes including motor vehicle collision, battlefield injuries or even falls from standing. Persistent limb pain is common after orthopedic injury or surgery and presents a unique challenge, as the initiating event may result in polytrauma to bone, muscle, and peripheral nerves. It is imperative that we understand the tissue-specific and multicellular response to this unique type of injury in order to best develop targeted treatments that improve healing and regeneration. In this Mini Review we will first discuss current rodent models of orthopedic trauma/complex orthotrauma. In the second section, we will focus on bone-specific outcomes including imaging modalities, biomechanical testing and immunostaining for markers of bone healing/turnover. In the third section, we will discuss muscle-related pathology including outcome measures of fibrosis, muscle regeneration and tensile strength measurements. In the fourth section, we will discuss nervous system-related pathology including outcome measures of pain-like responses, both reflexive and non-reflexive. In all sections we will consider parallels between preclinical outcome measures and the functional and mechanistic findings of the human condition.

Glycolytic reprogramming in macrophages and MSCs during inflammation

“…The crosstalk between Mφ and MSCs plays an important role in the development of skeletal diseases, as well as the maintenance of homeostasis of inflammatory microenvironments. For example, successful fracture healing depends on the coordinated cross-talk between Mφ and MSCs ( 39 , 69 ). Once the fractures and injured tissue triggered the recruitment of monocytes/macrophages, activated inflammatory M1-like Mφ were dominant in the early stage to clear cell debris and pathogens via pro-inflammatory cytokine release, contributing further to bone regeneration.…”

Impact of Adding Carpal Tunnel Release or Trigger Finger Release to Carpometacarpal Arthroplasty on Postoperative Complications”

“…[22][23][24] This makes inherent sense as disruption of tissue results in either direct injury of nociceptive primary afferents or indirect activation of these pain-producing neurons through local inflammation. 25 As a result, especially for patients at increased risk of postoperative pain, including those with preoperative pain at the surgical site, anxiety, or history of delayed recovery after injury, 26 combining surgical procedures for convenience may not result in the best outcome. Nevertheless, surgeon-patient decision-making should consider the implications of staging multiple procedures in the context of societal costs such as additional travel time, time away from work, and interruption to the patient's life.…”

Discovering chronic pain treatments: better animal models might help us get there

“…In response to the national discussion, there have been several rodent models developed recently with an eye to improving face validity (defined as the similarity in clinical signs and symptoms), construct validity (defined as similarity in pathophysiologic disease mechanisms), and predictive validity (defined as the relative effectiveness of various clinical interventions being mimicked by the model). Among these systems, models of complex regional pain syndrome (CPRS) ( 15 ), complex orthopedic trauma ( 16 ), temporomandibular joint pain ( 17 ), and a genetic model of widespread hyperalgesia ( 18 ) have been used effectively to determine pathophysiological mechanisms associated with these conditions.…”