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Excessive walking exercise precipitates diabetic neuropathic foot pain: hind paw suspension treadmill exercise experiment in a rat model.

ABSTRACT: The harmful effects of excessive mechanical loading on diabetic neuropathy and the reason diabetic neuropathic symptoms are common in feet are unclear. In this study, the hind paw suspension treadmill exercise model was used in rats to investigate whether mechanical loading applied to the front paws precipitates neuropathic pain, especially in diabetic conditions. Thirty-two rats were divided into six groups according to the presence of diabetes (DM) and the intensity of mechanical loading applied to the front paws: DM-Hi (high-intensity); DM-Lo (low-intensity); DM-No (non-mechanical loading); Sham-Hi; Sham-Lo; and Sham-No. DM was induced by streptozotocin injection. For high-intensity or low-intensity mechanical loading, treadmill walking exercise was conducted with or without hind paw suspension, respectively. The mechanical withdrawal threshold of the front paw decreased significantly after 8 weeks only in the DM mechanical loading groups (DM-Hi and DM-Lo), and high-intensity loading more significantly decreased the front-paw withdrawal threshold than low-intensity loading. In the DM-Hi group only, macrophage migration inhibitory factor (MIF) increased significantly, and intra-epidermal nerve fibers (IENF) in the front paws decreased significantly. In diabetic conditions, mechanical overloading such as excessive walking is likely to precipitate mechanical allodynia and damage IENF¸ which could explain why diabetic neuropathic symptoms are common in feet. This finding might be related to up-regulation of intracellular signaling cascades such as MIF, rather than inflammatory processes.

SUBMITTER: Do JG

PROVIDER: S-EPMC7319951 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceFew people with lower extremity peripheral artery disease (PAD) participate in supervised treadmill exercise covered by the Center for Medicare and Medicaid Services. In people with PAD, the benefits of home-based walking exercise, relative to supervised exercise, remain unclear.ObjectiveTo study whether home-based walking exercise improves 6-minute walk (6MW) more than supervised treadmill exercise in people with PAD (defined as Ankle Brachial Index ≤0.90).Data sourcesData were combined from 5 randomized clinical trials of exercise therapy for PAD using individual participant data meta-analyses, published from 2009 to 2022.Study selectionOf the 5 clinical trials, 3 clinical trials compared supervised treadmill exercise to nonexercise control (N = 370) and 2 clinical trials compared an effective home-based walking exercise intervention to nonexercise control (N = 349).Data extraction and synthesisIndividual participant-level data from 5 randomized clinical trials led by 1 investigative team were combined. The 5 randomized clinical trials included 3 clinical trials of supervised treadmill exercise and 2 effective home-based walking exercise interventions.Main outcomes and measuresChange in 6MW distance, maximum treadmill walking distance, and Walking Impairment Questionnaire at 6-month follow-up. The supervised treadmill exercise intervention consisted of treadmill exercise in the presence of an exercise physiologist, conducted 3 days weekly for up to 50 minutes per session. Home-based walking exercise consisted of a behavioral intervention in which a coach helped participants walk for exercise in or around home for up to 5 days per week for 50 minutes per session.ResultsA total of 719 participants with PAD (mean [SD] age, 68.8 [9.5] years; 46.5% female) were included (349 in a home-based exercise clinical trial and 370 in a supervised exercise trial). Compared with nonexercise control, supervised treadmill exercise was associated with significantly improved 6MW by 32.9 m (95% CI, 20.6-45.6; P < .001) and home-based walking exercise was associated with significantly improved 6MW by 50.7 m (95% CI, 34.8-66.7; P < .001). Compared with supervised treadmill exercise, home-based walking exercise was associated with significantly greater improvement in 6MW distance (between-group difference: 23.8 m [95% CI, 3.6, 44.0; P = .02]) but significantly less improvement in maximum treadmill walking distance (between-group difference:-132.5 m [95% CI, -192.9 to -72.1; P < .001]).Conclusions and relevanceIn this individual participant data meta-analyses, compared with supervised exercise, home-based walking exercise was associated with greater improvement in 6MW in people with PAD. These findings support home-based walking exercise as a first-line therapy for walking limitations in PAD.

Project description:The temporal dynamics of stride-to-stride fluctuations in steady-state walking reveal important information about locomotor control and can be quantified using so-called fractal analyses, notably the detrended fluctuation analysis (DFA). Gait dynamics are often collected during treadmill walking using 3-D motion capture to identify gait events from kinematic data. The sampling frequency of motion capture systems may impact the precision of event detection and consequently impact the quantification of stride-to-stride variability. This study aimed i) to determine if collecting multiple walking trials with different sampling frequency affects DFA values of spatiotemporal parameters during treadmill walking, and ii) to determine the reliability of DFA values across downsampled conditions. Seventeen healthy young adults walked on a treadmill while their gait dynamics was captured using different sampling frequency (60, 120 and 240 Hz) in each condition. We also compared data from the highest sampling frequency to downsampled versions of itself. We applied DFA to the following time series: step length, time and speed, and stride length, time and speed. Reliability between experimental conditions and between downsampled conditions were measured with 1) intraclass correlation estimates and their 95% confident intervals, calculated based on a single-measurement, absolute-agreement, two-way mixed-effects model (ICC 3,1), and 2) Bland-Altman bias and limits of agreement. Both analyses revealed a poor reliability of DFA results between conditions using different sampling frequencies, but a relatively good reliability between original and downsampled spatiotemporal variables. Collectively, our results suggest that using sampling frequencies of 120 Hz or 240 Hz provide similar results, but that using 60 Hz may alter DFA values. We recommend that gait kinematics should be collected at around 120 Hz, which provides a compromise between event detection accuracy and processing time.

Project description:Variability is ubiquitous in human movement, arising from internal and external noise, inherent biological redundancy, and from the neurophysiological control actions that help regulate movement fluctuations. Increased walking variability can lead to increased energetic cost and/or increased fall risk. Conversely, biological noise may be beneficial, even necessary, to enhance motor performance. Indeed, encouraging more variability actually facilitates greater improvements in some forms of locomotor rehabilitation. Thus, it is critical to identify the fundamental principles humans use to regulate stride-to-stride fluctuations in walking. This study sought to determine how humans regulate stride-to-stride fluctuations in stepping movements during treadmill walking. We developed computational models based on pre-defined goal functions to compare if subjects, from each stride to the next, tried to maintain the same speed as the treadmill, or instead stay in the same position on the treadmill. Both strategies predicted average behaviors empirically indistinguishable from each other and from that of humans. These strategies, however, predicted very different stride-to-stride fluctuation dynamics. Comparisons to experimental data showed that human stepping movements were generally well-predicted by the speed-control model, but not by the position-control model. Human subjects also exhibited no indications they corrected deviations in absolute position only intermittently: i.e., closer to the boundaries of the treadmill. Thus, humans clearly do not adopt a control strategy whose primary goal is to maintain some constant absolute position on the treadmill. Instead, humans appear to regulate their stepping movements in a way most consistent with a strategy whose primary goal is to try to maintain the same speed as the treadmill at each consecutive stride. These findings have important implications both for understanding how biological systems regulate walking in general and for being able to harness these mechanisms to develop more effective rehabilitation interventions to improve locomotor performance.

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Excessive walking exercise precipitates diabetic neuropathic foot pain: hind paw suspension treadmill exercise experiment in a rat model.

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