Gait Assessment of Pain and Analgesics: Comparison of the DigiGait™ and CatWalk™ Gait Imaging Systems

Xu, Yu; Tian, Na; Bai, Qingyang; Chen, Qi; Sun, Xiaohong; Wang, Yun

doi:10.1007/s12264-018-00331-y

Cited by 62 publications

(67 citation statements)

References 65 publications

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“…After intrafemur inoculation of LLC cells, mice developed mechanical allodynia and thermal hyperalgesia by posttumor day (PTD) 14 that persisted for at least 28 days in the ipsilateral hind paw ( Figure 1, A and B , 2 -way repeated measures [RM] ANOVA, treatments: F [3, 30] = 20.90, P < 0.001 for PWL; F [3, 30] = 24.31, P < 0.001 for PWT; treatment × time: F [12, 120] = 3.10, P < 0.001 for PWL; F [12, 120] = 1.97, P = 0.03 for PWT). CatWalk gait analysis can rapidly quantify several gait parameters, including the mean paw print area and stand and swing phases of the hind paw, which have been linked to mechanical allodynia and spontaneous pain in chronic pain ( 22 – 24 ). As shown in Figure 1, C–E , bone cancer mice exhibited a significant increase in swing phase (i.e., the duration of the paw not touching the glass plate) of the affected paw on PTDs 21 and 28 (2-way RM ANOVA, treatments: F [1, 15] = 14.52, P < 0.001; treatment × time: F [4, 60] = 4.40, P < 0.001).…”

Section: Resultsmentioning

confidence: 99%

“…The CatWalk system (XT, Noldus Information Technology, Wageningen, the Netherlands) was used for the quantitative assessment of gait parameter and footfalls in rodents. Gait analysis has proved a reliable method for measuring pain-associated behaviors, based on the voluntary movement of rodents in an enclosed walkway ( 24 , 76 , 77 ). Briefly, the mouse was placed in the open end of the enclosed glass platform in a darkened room with a red ceiling light-emitting diode light and allowed to walk voluntarily through the walkway.…”

Section: Methodsmentioning

confidence: 99%

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Inhibition of TRPV1 by SHP-1 in nociceptive primary sensory neurons is critical in PD-L1 analgesia

Liu¹,

Cao²,

Zhao³

et al. 2020

JCI Insight

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Recently programmed death-ligand 1 (PD-L1) receptor PD-1 was found in dorsal root ganglion (DRG) neurons, and PD-L1 activates PD-1 to inhibit inflammatory and neuropathic pain by modulating neuronal excitability. However, the downstream signaling of PD-1 in sensory neurons remains unclear. Here, we show that PD-L1 activated Src homology 2 domain-containing tyrosine phosphatase-1 (SHP-1) to downregulate transient receptor potential vanilloid 1 (TRPV1) in DRG neurons and inhibit bone cancer pain in mice. Local injection of PD-L1 produced analgesia. PD-1 in DRG neurons colocalized with TRPV1 and SHP-1. PD-L1 induced the phosphorylation of SHP-1 in DRG TRPV1 neurons and inhibited TRPV1 currents. Loss of TRPV1 in mice abolished bone cancer–induced thermal hyperalgesia and PD-L1 analgesia. Conditioned deletion of SHP-1 in Na V 1.8 + neurons aggravated bone cancer pain and diminished the inhibition of PD-L1 on TRPV1 currents and pain. Together, our findings suggest that PD-L1/PD-1 signaling suppresses bone cancer pain via inhibition of TRPV1 activity. Our results also suggest that SHP-1 in sensory neurons is an endogenous pain inhibitor and delays the development of bone cancer pain via suppressing TRPV1 function.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Inhibition of TRPV1 by SHP-1 in nociceptive primary sensory neurons is critical in PD-L1 analgesia

Liu¹,

Cao²,

Zhao³

et al. 2020

JCI Insight

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show abstract

“…Alongside a large number of studies on experimental osteoarthritis ( 18 ), recent preclinical studies have tested the efficacy of automated gait analysis systems in murine models of neuropathic pain by spinal nerve injury ( 30 , 35 , 36 ), chronic constriction injury-induced pain [AU—( 37 )], CFA-induced pain ( 35 , 36 ), paclitaxel-induced polyneuropathy ( 38 ) and post-operative pain in bone-reconstruction surgery ( 39 ). Commercially available systems such as CatWalk XT (Noldus) and GaitLab (ViewPoint Behavior Technology) rely on imaging paw prints reflected internally across an elevated glass floor where the animal walks ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal Alterations in Gait in Humanized Transgenic Sickle Mice

et al. 2020

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Sickle cell disease (SCD) is a hemoglobinopathy affecting multiple organs and featuring acute and chronic pain. Purkinje cell damage and hyperalgesia have been demonstrated in transgenic sickle mice. Purkinje cells are associated with movement and neural function which may influence pain. We hypothesized that Purkinje cell damage and/or chronic pain burden provoke compensatory gait changes in sickle mice. We found that Purkinje cells undergoe increased apoptosis as shown by caspase-3 activation. Using an automated gait measurement system, MouseWalker, we characterized spatiotemporal gait characteristics of humanized transgenic BERK sickle mice in comparison to control mice. Sickle mice showed alteration in stance instability and dynamic gait parameters (walking speed, stance duration, swing duration and specific swing indices). Differences in stance instability may reflect motor dysfunction due to damaged Purkinje cells. Alterations in diagonal and all stance indices indicative of hesitation during walking may originate from motor dysfunction and/or arise from fear and/or anticipation of movement-evoked pain. We also demonstrate that stance duration, diagonal swing indices and all stance indices correlate with both mechanical and deep tissue hyperalgesia, while stance instability correlates with only deep tissue hyperalgesia. Therefore, objective analysis of gait in SCD may provide insights into neurological impairment and pain states.

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“…The application of machine learning furthered establishing a grimace scale in mammals as an indicator for pain ( Langford et al, 2010 ; Sotocinal et al, 2011 ; Andresen et al, 2020 ). Automated analysis systems for the walking behavior of rodents are discussed as an objective assessment of spontaneous and ongoing pain behavior in rodents ( Vrinten and Hamers, 2003 ; Xu et al, 2019 ). Even in fruit flies, small changes in wing angle could be associated with the activity of specific neurons ( Robie et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Current Methods to Investigate Nociception and Pain in Zebrafish

2021

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Pain is an unpleasant, negative emotion and its debilitating effects are complex to manage. Mammalian models have long dominated research on nociception and pain, but there is increasing evidence for comparable processes in fish. The need to improve existing pain models for drug research and the obligation for 3R refinement of fish procedures facilitated the development of numerous new assays of nociception and pain in fish. The zebrafish is already a well-established animal model in many other research areas like toxicity testing, as model for diseases or regeneration and has great potential in pain research, too. Methods of electrophysiology, molecular biology, analysis of reflexive or non-reflexive behavior and fluorescent imaging are routinely applied but it is the combination of these tools what makes the zebrafish model so powerful. Simultaneously, observing complex behavior in free-swimming larvae, as well as their neuronal activity at the cellular level, opens new avenues for pain research. This review aims to supply a toolbox for researchers by summarizing current methods to study nociception and pain in zebrafish. We identify treatments with the best algogenic potential, be it chemical, thermal or electric stimuli and discuss options of analgesia to counter effects of nociception and pain by opioids, non-steroidal anti-inflammatory drugs (NSAIDs) or local anesthetics. In addition, we critically evaluate these practices, identify gaps of knowledge and outline potential future developments.

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Gait Assessment of Pain and Analgesics: Comparison of the DigiGait™ and CatWalk™ Gait Imaging Systems

Cited by 62 publications

References 65 publications

Inhibition of TRPV1 by SHP-1 in nociceptive primary sensory neurons is critical in PD-L1 analgesia

Inhibition of TRPV1 by SHP-1 in nociceptive primary sensory neurons is critical in PD-L1 analgesia

Spatiotemporal Alterations in Gait in Humanized Transgenic Sickle Mice

Current Methods to Investigate Nociception and Pain in Zebrafish

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