Dataset Information

Modeling foot sole cutaneous afferents: FootSim.

ABSTRACT: While walking and maintaining balance, humans rely on cutaneous feedback from the foot sole. Electrophysiological recordings reveal how this tactile feedback is represented in neural afferent populations, but obtaining them is difficult and limited to stationary conditions. We developed the FootSim model, a realistic replication of mechanoreceptor activation in the lower limb. The model simulates neural spiking responses to arbitrary mechanical stimuli from the combined population of all four types of mechanoreceptors innervating the foot sole. It considers specific mechanics of the foot sole skin tissue, and model internal parameters are fitted using human microneurography recording dataset. FootSim can be exploited for neuroscientific insights, to understand the overall afferent activation in dynamic conditions, and for overcoming the limitation of currently available recording techniques. Furthermore, neuroengineers can use the model as a robust in silico tool for neuroprosthetic applications and for designing biomimetic stimulation patterns starting from the simulated afferent neural responses.

SUBMITTER: Katic N

PROVIDER: S-EPMC9829801 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Modeling foot sole cutaneous afferents: FootSim.

Katic Natalija N Siqueira Rodrigo Kazu RK Cleland Luke L Strzalkowski Nicholas N Bent Leah L Raspopovic Stanisa S Saal Hannes H

iScience 20221224 1

While walking and maintaining balance, humans rely on cutaneous feedback from the foot sole. Electrophysiological recordings reveal how this tactile feedback is represented in neural afferent populations, but obtaining them is difficult and limited to stationary conditions. We developed the FootSim model, a realistic replication of mechanoreceptor activation in the lower limb. The model simulates neural spiking responses to arbitrary mechanical stimuli from the combined population of all four ty ...[more]

PMID: 36636355

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Project description:Neurotrophic factors play an important role in the regulation of functional properties of sensory neurons under normal and pathological conditions. The GDNF family member neurturin is one such factor that has been linked to modulating responsiveness to peripheral stimuli. Neurturin binds to the GFRα2 receptor, a receptor found primarily in isolectin B4-expressing polymodal cutaneous nociceptors. Previous work has shown that knockout of GFRα2 alters heat, but not mechanical, responses in dissociated sensory neurons and reduces pain-related behaviors during the second phase of the formalin test. Research has also shown that overexpression of neurturin in basal keratinocytes increases behavioral responsiveness to mechanical stimulation and innocuous cooling of the skin without affecting noxious heat responses. Here we directly examined the impact of neurturin overexpression on cutaneous afferent function. We compared physiological responses of individual sensory neurons to mechanical and thermal stimulation of the skin, using an ex vivo skin-nerve-dorsal root ganglion-spinal cord preparation produced from neurturin-overexpressing (NRTN/OE) mice and wild-type littermate controls. We found that neurturin overexpression increases responsiveness to innocuous mechanical stimuli in A-fiber nociceptors, alters thermal responses in the polymodal subpopulation of C-fiber sensory neurons, and changes the relative numbers of mechanically sensitive but thermally insensitive C-fiber afferents. These results demonstrate the potential roles of different functional groups of sensory neurons in the behavioral changes observed in mice overexpressing cutaneous neurturin and highlight the importance of neurturin in regulating cutaneous afferent response properties.NEW & NOTEWORTHY GDNF family neurotrophic factors regulate the development and function of primary sensory neurons. Of these, neurturin has been shown to modulate mechanical and cooling sensitivity behaviorally. Here we show that overexpression of neurturin in basal keratinocytes regulates mechanical responsiveness in A-fiber primary sensory neurons while increasing the overall numbers of cold-sensing units. Results demonstrate a crucial role for cutaneous neurturin in modulating responsiveness to peripheral stimuli at the level of the primary afferent.

Project description:BackgroundHorses with palmar foot pain do not show a typical increase in temperature in the palmar aspect of the hoof and heel due to low blood flow. The objectives of the current study were to determine the changes and differences in the thermographic pattern of the sole surface in horses with unilateral palmar foot pain and non-lame horses before and after training. We hypothesized that the thermal pattern and the local temperature of the frog area and toe area would be similar, with an increased local temperature after training in both lame and non-lame horses. A pilot study was conducted to investigate the accuracy of thermography used to detect changes in local temperature and to compare the thermal patterns observed on the sole surface after training.MethodsThe study group included eight horses with unilateral forelimb palmar foot pain (n = 8) and healthy contralateral limbs (n = 8). Four additional non-lame horses served as controls. The horses were selected for the study based on the following criteria: forelimb with unilateral chronic progressive lameness and positive reactions when performing the hoof test and frog wedge test, degenerative findings of the navicular bone, and improvement in lameness after perineural analgesia of the medial and lateral palmar digital nerve. The local temperatures of the frog and toe areas were measured before and after training in the affected and contralateral limbs in the study group and both forelimbs in the control group using an FLIR E50 thermal camera. Receiver operating characteristic (ROC) curve analysis was applied to check the sensitivity and specificity of the results for the studied groups.ResultsThe thermal patterns of the hoof presented differences between the three groups of horse limbs. After training, the temperature of the sole surface increased, and its area increased in the limbs affected with palmar foot pain compared with the non-lame limbs in the study group and the limbs in the control group. The temperature of the frog area did not increase after training in the limbs affected with palmar foot pain compared with the same area in the other groups. The ROC curve analysis demonstrated the medical applicability of this tool and showed that thermography is a reliable diagnostic test to correctly discriminate between non-lame horses and those with palmar foot pain.ConclusionsWe recommend thermographic scanning of the toe and frog area to detect changes in the local temperature of the sole surface after training to discriminate the horses with palmar foot pain from non-lame ones. Further investigation is required to clarify whether the observed thermographic imaging features of the sole surface are characteristic for horses with palmar foot pain.

Dataset Information

Modeling foot sole cutaneous afferents: FootSim.

Publications

Modeling foot sole cutaneous afferents: FootSim.

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