Gait analysis correlates mechanical hyperalgesia in a model of streptozotocin-induced diabetic neuropathy: A CatWalk dynamic motor function study

Vieira, Willians Fernando; Malange, Kauê Franco; Magalhães, Silviane Fernandes de; Santos, Gilson Gonçalves dos; Oliveira, Alexandre Leite Rodrigues de; Cruz‐Höfling, Maria Alice da

doi:10.1016/j.neulet.2020.135253

Cited by 14 publications

(9 citation statements)

References 59 publications

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“…Gait analysis was performed using the CatWalk XT system (Noldus, the Netherlands), which has been proven a very reliable method for measuring pain-related behaviors [ 87 ]. The mouse was placed on the open end of an enclosed glass platform and walked across the glass floor voluntarily, during which a high-speed camera underneath the device captured images of each paw and transmitted the data to gait analysis software (CatWalk XT, version 10.6; Noldus) [ 46 , 88 ]. In this study, eight available parameters were identified to assess the dynamic behaviors relevant to NP [ 88 , 89 ]: (1) regularity index as the degree of inter-limb coordination as a percentage of complete coordination; (2) stand as the duration of a paw touching the glass plate; (3) body speed is calculated by counting the distance of the mouse's body (paws) from the initial contact with the glass plate to the next contact divided by the time required to move this distance; (4) standing on three as the percentage of time spent walking with three paws; (5) print length as the length of the paw print (horizontal direction); (6) print width as the width of the complete paw print (vertical direction); (7) max contact area as the maximum print area during paw contact; and (8) max contact mean intensity as the mean intensity at maximum paw contact.…”

Section: Methodsmentioning

confidence: 99%

Targeted up-regulation of Drp1 in dorsal horn attenuates neuropathic pain hypersensitivity by increasing mitochondrial fission

Zhang

et al. 2022

Redox Biology

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Mitochondria play an essential role in pathophysiology of both inflammatory and neuropathic pain (NP), but the mechanisms are not yet clear. Dynamin-related protein 1 (Drp1) is broadly expressed in the central nervous system and plays a role in the induction of mitochondrial fission process. Spared nerve injury (SNI), due to the dysfunction of the neurons within the spinal dorsal horn (SDH), is the most common NP model. We explored the neuroprotective role of Drp1 within SDH in SNI. SNI mice showed pain behavior and anxiety-like behavior, which was associated with elevation of Drp1, as well as increased density of mitochondria in SDH. Ultrastructural analysis showed SNI induced damaged mitochondria into smaller perimeter and area, tending to be circular. Characteristics of vacuole in the mitochondria further showed SNI induced the increased number of vacuole, widened vac-perimeter and vac-area. Stable overexpression of Drp1 via AAV under the control of the Drp1 promoter by intraspinal injection (Drp1 OE) attenuated abnormal gait and alleviated pain hypersensitivity of SNI mice. Mitochondrial ultrastructure analysis showed that the increased density of mitochondria induced by SNI was recovered by Drp1 OE which, however, did not change mitochondrial morphology and vacuole parameters within SDH. Contrary to Drp1 OE, down-regulation of Drp1 in the SDH by AAV-Drp1 shRNA (Drp1 RNAi) did not alter painful behavior induced by SNI. Ultrastructural analysis showed the treatment by combination of SNI and Drp1 RNAi (SNI + Drp1 RNAi) amplified the damages of mitochondria with the decreased distribution density, increased perimeter and area, as well as larger circularity tending to be more circular. Vacuole data showed SNI + Drp1 RNAi increased vacuole density, perimeter and area within the SDH mitochondria. Our results illustrate that mitochondria within the SDH are sensitive to NP, and targeted mitochondrial Drp1 overexpression attenuates pain hypersensitivity. Drp1 offers a novel therapeutic target for pain treatment.

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Section: Methodsmentioning

confidence: 99%

Targeted up-regulation of Drp1 in dorsal horn attenuates neuropathic pain hypersensitivity by increasing mitochondrial fission

Zhang

et al. 2022

Redox Biology

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“…Max contact mean intensity is a measure of weight borne on a foot at the time of maximum contact with the CatWalk platform. It's worth noting that max contact mean intensity has been used as an indicator of pain in previous studies of diabetic neuropathy, and much smaller sciatic crush/transection injuries, but has not been confirmed as an indicator of pain in large transection studies such as this study (Vrinten and Hamers, 2003;Deumens et al, 2007;Vieira et al, 2020). Max contact mean intensity is here used as a measure of weight borne on the foot as an indicator of LH function.…”

Section: Discussionmentioning

confidence: 84%

The effects of graft source and orientation on outcomes after ablation of a branched peripheral nerve

Allgood

Roballo

Sparks

et al. 2022

Front. Cell. Neurosci.

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Segmental peripheral nerve injuries (PNI) are the most common cause of enduring nervous system dysfunction. The peripheral nervous system (PNS) has an extensive and highly branching organization. While much is known about the factors that affect regeneration through sharp bisections and linear ablations of peripheral nerves, very little has been investigated or documented about PNIs that ablate branch points. Such injuries present additional complexity compared to linear segmental defects. This study compared outcomes following ablation of a branch point with branched grafts, specifically examining how graft source and orientation of the branched graft contributed to regeneration. The model system was Lewis rats that underwent a 2.5 cm ablation that started in the sciatic nerve trunk and included the peroneal/tibial branch point. Rats received grafts that were rat sciatic autograft, inbred sciatic allograft, and inbred femoral allograft, each of which was a branched graft of 2.5 cm. Allografts were obtained from Lewis rats, which is an inbred strain. Both branches of the sciatic grafts were mixed motor and sensory while the femoral grafts were smaller in diameter than sciatic grafts and one branch of the femoral graft is sensory and the other motor. All branched grafts were sutured into the defect in two orientations dictated by which branch in the graft was sutured to the tibial vs peroneal stumps in recipients. Outcome measures include compound muscle action potentials (CMAPs) and CatWalk gait analysis throughout the recovery period, with toluidine blue for intrinsic nerve morphometry and retrograde labeling conducted at the 36-week experimental end point. Results indicate that graft source and orientation does play a significant role earlier in the regenerative process but by 36 weeks all groups showed very similar indications of regeneration across multiple outcomes.

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“…Quantitative data include static and dynamic paw parameters, and coordination parameters. The authors showed that the assessment has been used mostly for nerve injury [5], arthritis [55], modelling pain [50], but also in a few studies for neurodegenerative diseases that affect the gait [15]. The system was developed to evaluate footfall and gait changes, and it can calculate 25 parameters based on footprints and 10 parameters based on time interval.…”

Section: Discussion Regarding General Outlines Using Computerized Gait Analysis System and Its Effectiveness In In Vivo Experimentsmentioning

confidence: 99%

“…Alterations in the spatial parameters (e.g., Maximum Contact Area; Stride Length; Print Area) were correlated with the mechanical withdrawal thresholds. Authors point out in this recent study that the CW gait parameters are a good complementary tool to investigate the development of hyperalgesia diabetic neuropathy [50].…”

Section: Peripheral Nerve Injurymentioning

confidence: 99%

Gait Analysis Using Animal Models of Peripheral Nerve and Spinal Cord Injuries

2021

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The present review discusses recent data regarding rodent models of spinal cord and peripheral nerve injuries in terms of gait analysis using the CatWalk system (CW), an automated and exceptionally reliable system for assessing gait abnormalities and motor coordination. CW is a good tool for both studying improvements in the walking of animals after suffering a peripheral nerve and spinal cord lesion and to select the best therapies and procedures after tissue destruction, given that it provides objective and quantifiable data. Most studies using CW for gait analysis that were published in recent years focus on injuries inflicted in the peripheral nerve, spinal cord, and brain. CW has been used in the assessment of rodent motor function through high-resolution videos, whereby specialized software was used to measure several aspects of the animal’s gait, and the main characteristics of the automated system are presented here. CW was developed to assess footfall and gait changes, and it can calculate many parameters based on footprints and time. However, given the multitude of parameters, it is necessary to evaluate which are the most important under the employed experimental circumstances. By selecting appropriate animal models and evaluating peripheral nerve and spinal cord lesion regeneration using standardized methods, suggestions for new therapies can be provided, which represents the translation of this methodology into clinical application.

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Gait analysis correlates mechanical hyperalgesia in a model of streptozotocin-induced diabetic neuropathy: A CatWalk dynamic motor function study

Cited by 14 publications

References 59 publications

Targeted up-regulation of Drp1 in dorsal horn attenuates neuropathic pain hypersensitivity by increasing mitochondrial fission

Targeted up-regulation of Drp1 in dorsal horn attenuates neuropathic pain hypersensitivity by increasing mitochondrial fission

The effects of graft source and orientation on outcomes after ablation of a branched peripheral nerve

Gait Analysis Using Animal Models of Peripheral Nerve and Spinal Cord Injuries

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