Objective and Quantitative Evaluation of Spontaneous Pain-Like Behaviors Using Dynamic Weight-Bearing System in Mouse Models of Postsurgical Pain

Abstract

Background The paucity of objective and reliable measurements of pain-like behaviors has impeded the translatability of mouse models of postsurgical pain. The advanced dynamic weight-bearing (DWB) system enables evaluation of spontaneous pain-like behaviors in pain models. This study investigated the suitability and efficiency of the DWB system for assessing spontaneous pain-like behaviors and analgesic therapies in murine models of postsurgical pain. Methods Male adult C57BL/6JJcl mice were subjected to multiple surgical pain models with distinct levels of invasiveness, including a superficial incisional pain model involving only hind paw skin incision, deep incisional pain model that also involved incision and elevation of the underlying hind paw muscles, and orthopedic pain model involving tibial bone fracture and fixation with a pin (fracture and pinning [F/P] model). Spontaneous pain-like behaviors post-surgery were evaluated using weight distribution, pawprint area of the operated paw in the DWB system, and guarding pain score. Mechanical hypersensitivity was assessed using the von Frey test. The therapeutic effects of analgesics (diclofenac and buprenorphine for the deep incision model and diclofenac for the F/P model) were evaluated using the DWB system and von Frey test. Results The von Frey test demonstrated contradictory results between superficial and deep incisional pain models. The DWB system captured weight distribution changes in the operated hind paw, in accordance with the invasiveness and time course of wound healing in these surgical pain models. The reduction in weight-bearing on the operated paw correlated with guarding score, degree of paw swelling, and local expression of inflammatory mediators. DWB enabled accurate evaluation of the pharmacological effects of analgesics for detecting attenuation of surgery-induced weight-bearing changes in these models. Conclusion The DWB system serves as an objective and reliable method for quantifying pain-like behaviors and evaluating the therapeutic effects of analgesics in mouse models of postsurgical pain models.

Advanced Dynamic Weight Bearing as an Observer-independent Measure of Hyperacute Hypersensitivity in Mice

“…Though only male mice were used, our study provides a proof-of-concept methodology for future studies using ADWB. Additional work will be necessary to further demonstrate the utility of ADWB in detecting and evaluating analgesic effects of currently available therapeutics 30 and/or testing preclinical TRPA1 inhibitors. 69 However, others have shown that this system can detect changes in response to drugs such as diclofenac, indomethacin, and celecoxib in various models of acute and chronic pain.…”

“…The ADWB allows for (1) the animal to freely explore its environment, facilitating the study of behavioral responses to nonreflexive mechanical hypersensitivity, 28 and (2) the objective measurement of both paw weight and surface area, eliminating bias in the data collection process. To date, this tool has been used to study a range of pain conditions (e.g., postoperative pain, 29 , 30 cancer-induced bone pain, 31 inflammatory hyperalgesia, 32 neuropathic pain, 33 , 34 and osteo- and inflammatory arthritis) 35 , 36 as well as neurological diseases including vestibulopathy 37 and multiple sclerosis. 38 …”

“…Though some have suggested that dynamic weight bearing can be used as a measure of neuropathic 33 , 34 or spontaneous pain-like behaviors, 30–32 there have been contradictory findings with the use of weight bearing as a measure of chronic pain. For instance, there are conflicting views as to the utility of weight bearing as a measure of pain after specific chronic injury models.…”

Pharmacological Ischemic Conditioning with Roxadustat Does Not Affect Pain-Like Behaviors but Mitigates Sudomotor Impairment in a Murine Model of Deep Hind Paw Incision

“…Spontaneous limb pain-like behaviors were assessed using an advanced DWB apparatus (Bioseb, Vitrolles, Provence-Alpes-Côte D’Azur, France; catalog number: BIO-DWB-M), wherein changes in the postural equilibrium of each freely moving animal were tracked and analyzed. 20 The animal was placed in a transparent enclosure for 1 min for acclimatization, followed by a 5-min recording. A matrix comprising pressure sensors capturing the weight distribution data of each of the four paws was embedded in the floor.…”

A Novel Rat Model to Study Postsurgical Pain After Joint Replacement Surgery

“…18 Stimulus-evoked responses, such as the von Frey test, have been widely used in pain research to assess pain-related behavior. However, we selected DWB in this study because asymmetric weight distribution partially reflects spontaneous pain during free walking in unilateral paw pain models, [25][26][27] which appears to be more relevant and clinically important for assessing our novel JR model.…”