Toe Spread Research Articles

Development of a mouse model of chronic ventral spinal cord compression: Neurobehavioral, radiological, and pathological changes.

The main objective of this study was to establish a mouse model of spinal ligament ossification to simulate the chronic spinal cord compression observed in patients with ossification of the posterior longitudinal ligament (OPLL). The study also aimed to examine the mice's neurobiological, radiological, and pathological changes. In the previous study, a genetically modified mouse strain was created using Crispr-Cas9 technology, namely, Enpp1 flox/flox /EIIa-Cre (C57/B6 background), to establish the OPLL model. Wild-type (WT) mice without compression were used as controls. Functional deficits were evaluated through motor score assessment, inclined plate testing, and gait analysis. The extent of compression was determined using CT imaging. Hematoxylin and eosin staining, luxol fast blue staining, TUNEL assay, immunofluorescence staining, qPCR, and Western blotting were performed to evaluate levels of apoptosis, inflammation, vascularization, and demyelination in the study. The results demonstrated a gradual deterioration of compression in the Enpp1 flox/flox /EIIa-Cre mice group as they aged. The progression rate was more rapid between 12 and 20 weeks, followed by a gradual stabilization between 20 and 28 weeks. The scores for spinal cord function and strength, assessed using the Basso Mouse Scale and inclined plate test, showed a significant decline. Gait analysis revealed a noticeable reduction in fore and hind stride lengths, stride width, and toe spread. Chronic spinal cord compression resulted in neuronal damage and activated astrocytes and microglia in the gray matter and anterior horn. Progressive posterior cervical compression impeded blood supply, leading to inflammation and Fas-mediated neuronal apoptosis. The activation of Bcl2 and Caspase 3 was associated with the development of progressive neurological deficits (p < 0.05). The study presents a validated model of chronic spinal cord compression, enabling researchers to explore clinically relevant therapeutic approaches for OPLL.

In silico model for automated calculation of functional metrics in animal models of peripheral nerve injury repair

The rat sciatic nerve model is commonly used to test novel therapies for nerve injury repair. The static sciatic index (SSI) is a useful metric for quantifying functional recovery, and involves comparing an operated paw versus a control paw using a weighted ratio between the toe spread and the internal toe spread. To calculate it, rats are placed in a transparent box, photos are taken from underneath and the toe distances measured manually. This is labour intensive and subject to human error due to the challenge of consistently taking photos, identifying digits and making manual measurements. Although several commercial kits have been developed to address this challenge, they have seen little dissemination due to cost. Here we develop a novel algorithm for automatic measurement of SSI metrics based on video data using casted U-Nets. The algorithm consists of three U-Nets, one to segment the hind paws and two for the two pairs of digits which input into the SSI calculation. A training intersection over union error of 60 % and 80 % was achieved for the back paws and for both digit segmentation U-Nets, respectfully. The algorithm was tested against video data from three separate experiments. Compared to manual measurements, the algorithm provides the same profile of recovery for every experiment but with a tighter standard deviation in the SSI measure. Through the open-source release of this algorithm, we aim to provide an inexpensive tool to more reliably quantify functional recovery metrics to the nerve repair research community.

Cilostazol Ameliorates Motor Dysfunction and Schwann Cell Impairment in Streptozotocin-Induced Diabetic Rats.

This study investigated the effects of cilostazol on motor dysfunction, spinal motor neuron abnormalities, and schwannopathy in rats with diabetes. Diabetes mellitus (DM) was induced in rats via femoral intravenous streptozotocin (STZ) injection (60 mg/kg). After successful DM induction, cilostazol was administered on day 15 via oral gavage (100 mg/kg/day) for 6 weeks until sacrifice. Behavioral assays, including motor function, were performed weekly. The sciatic nerve, L5 spinal cord, and spinal ventral root were collected to evaluate the expression of the glial fibrillary acidic protein (GFAP), myelin protein zero (P0), and choline acetyltransferase (ChAT) by immunofluorescence and Western blotting. DM rats displayed decreased running speeds, running distances, and toe spread but increased foot pressure. In addition, loss of non-myelinating Schwann cells and myelin sheaths was observed in the sciatic nerve and L5 spinal ventral root. Reduced numbers of motor neurons were also found in the L5 spinal ventral horn. Cilostazol administration significantly potentiated running speed and distance; increased hind paw toe spread; and decreased foot pressure. In the sciatic nerve and L5 spinal ventral root, cilostazol treatment significantly improved non-myelinated Schwann cells and increased myelin mass. ChAT expression in motor neurons in the spinal ventral horn was improved, but not significantly. Cilostazol administration may protect sensorimotor function in diabetic rats.

Transplantation of Neural Progenitor Cells Derived from Stem Cells from Apical Papilla Through Small-Molecule Induction in a Rat Model of Sciatic Nerve Injury

Background:Stem cell-based transplantation therapy holds promise for peripheral nerve injury treatment, but adult availability is limited. A cell culture protocol utilizing a small-molecule cocktail effectively reprogrammed stem cells from apical papilla (SCAPs) into neural progenitor cells, subsequently differentiating into neuron-like cells. This study aims to evaluate neural-induced SCAPs, with and without small-molecule cocktail, for sciatic nerve repair potential.Methods:A scaffold-free cell sheet technique was used to construct a three-dimensional cell sheet. Subsequently, this cell sheet was carefully rolled into a tube and seamlessly inserted into a collagen conduit, which was then transplanted into a 5 mm sciatic nerve injury rat model. Functional sciatic nerve regeneration was evaluated via toe spread test, walking track analysis and gastrocnemius muscle weight. Additionally, degree of sciatic nerve regeneration was determined based on total amount of myelinated fibers.Results:Small-molecule cocktail induced SCAPs enhanced motor function recovery, evident in improved sciatic function index and gastrocnemius muscle retention. We also observed better host myelinated fiber retention than undifferentiated SCAPs or neural-induced SCAPs without small-molecule cocktail. However, clusters of neuron-like cell bodies (surrounded by sparse myelinated fibers) were found in all cell sheet-implanted groups in the implantation region. This suggests that while the implanted cells likely survived transplantation, integration was poor and would likely hinder long-term recovery by occupying the space needed for host nerve fibers to project through.Conclusion:Neural-induced SCAPs with small-molecule cocktail demonstrated promising benefits for nerve repair; further research is needed to improve its integration and optimize its potential for long-term recovery.

A comparison of abductor hallucis muscle activation and medial longitudinal arch angle during nine different foot exercises

BackgroundIntrinsic foot muscles are known to support the medial longitudinal arch (MLA) and stabilize the foot, and they are activated with weight bearing and increased postural demand. Various types of intrinsic foot muscle training have been reported, but one of the most useful of these, the short foot exercise, is challenging to perform effectively and requires practice, making it difficult to implement in ordinary clinical settings. Research questionWhat are the differences in abductor hallucis longus (ABH) muscle activity and MLA angle during intrinsic foot muscle exercises that employ weight bearing and balancing conditions when they are performed with minimal practice? MethodsSixteen healthy volunteers performed nine different intrinsic foot muscle exercises, practiced once or twice. The exercises consisted of toe curl, short foot without pushing, short foot with pushing and toe spread exercises in sitting and standing positions, and single leg swing in a standing position. Each exercise was performed three times for five seconds. The activities of the ABH muscles were measured using surface electromyographic (EMG) sensors and the MLA angles during the exercises were captured using an optical motion tracking system. The integrals of the ABH EMG signals were calculated. ResultsDifferences in the integral and maximum of the ABH EMG signal were found between the exercises (p < 0.001). Post-hoc pair-wise analysis revealed that the EMG activity was larger during the swing exercise than in exercises other than toe spread, both in sitting and standing positions, and short foot exercise with pushing while standing. The minimum MLA angle during each exercise was smaller for the toe spread exercise in a sitting position than other exercises (p < 0.023). SignificanceA single leg swing exercise may be effective for self-exercise of intrinsic foot muscles, particularly when intensive supervised physiotherapy is not possible.

The Efficacy of Low-Level Laser Therapy and Low Intensity Pulsed Ultrasound on Functional Recovery among Experimentally Induced Peripheral Nerve Injury in Wistar Rats

Background: A variety of etiological factors that lead to peripheral nerve injury include crushing, traction, longfractures in bones, cutting injuries, entrapment neuropathies, infection, inflammation, and tumours of varyingdegrees. LIPUS has a variety of biological effects on tissues, including speeding up the regeneration of soft tissues,and lowering inflammatory reactions. In LLLT, low-level laser light with a wavelength of 808 nm is employed totrigger a biological reaction.Purpose: The objective of this study was to evaluate the functional recovery of low-level laser therapy (LLLT) andlow-intensity pulsed ultrasound (LIPUS) treating the sciatic nerve in rats.Methods: Using simple random sampling method and the inclusion and exclusion criteria, 18 rats in total werechosen. A mechanical crush will be performed for 30 seconds using haemostatic forceps. The study’s rats weredivided into 3 groups at random: Group A received ultrasound for 21 days; Group B received laser for 21 days;and Group C received no treatment. The toe spread assay was used to assess functional recovery 3 weeks aftersurgery. Result: All three groups are statistically significant (p&lt;0.005) when analysed using one-way ANOVAduring intervention period (7th, 24th, 21st day) but LLLT &amp; UST has shown better improvement in their functionalindex than the control group.Conclusion: According to the study’s findings, LLLT significantly outperforms LIPUS in improving the functionalrecovery of an experimentally induced rat model.

Comparison of abductor hallucis muscle activity in subjects with mild hallux valgus during three different foot exercises.

Normal alignment of the foot is important because the feet support the body's weight. The intrinsic muscles of the foot mainly maintain the alignment and movement of the foot, whereas the abductor hallucis (AbdH) aligns the first metatarsophalangeal joint and maintains the medial longitudinal arch. This study was conducted to investigate the muscle activity of the AbdH and hallux valgus (HV) angle during three different foot exercises. Participants included 15 subjects aged 20-24 years with mild HV. All subjects performed three different foot exercises in random order: short foot exercise (SF), toe spread out exercise (TSO), and TSO with a pressure bio-feedback unit (TSOP). The muscle activity of the AbdH and the HV angle were measured during each foot exercise using surface electromyography and X-ray and then compared using one-way repeated-measures analysis of variance, followed by Bonferroni adjustment. AbdH muscle activity differed significantly among SF, TSO, and TSOP. AbdH muscle activity was greater in TSOP (89.60%) than in SF (19.99%) and TSO (60.96%) (p= 0.006). The HV angle was significantly smaller in TSOP (15.72∘) than in SF (18.85∘) and TSO (16.81∘) (p= 0.001). TSOP can be recommended as an effective AbdH strengthening exercise in subjects with mild HV.

Retrograde peripheral nerve regeneration from sensory to motor pathways in rats: a new experimental concept in nerve repair

ABSTRACT Background The polarity of nerve grafts does not interfere with axon growth. Our goal was to investigate whether axons can regenerate in a retrograde fashion within sensory pathways and then extend into motor pathways, leading to muscle reinnervation. Methods Fifty-four rats were randomized into four groups. In Group 1, the ulnar nerve was connected end-to-end to the superficial radial nerve after neurectomy of the radial nerve in the axilla. In Group 2, the ulnar nerve was connected end-to-end to the radial nerve distal to the humerus; the radial nerve then was divided in the axilla. In Group 3, the radial nerve was divided in the axilla, but no nerve reconstruction was performed. In Group 4, the radial nerve was crushed in the axilla. Over 6 months, we behaviorally assessed the recovery of toe spread in the right operated-upon forepaw by lifting the rat by its tail and lowering it onto a flat surface. Six months after surgery, rats underwent reoperation, nerve transfers were tested electrophysiologically, and the posterior interosseous nerve (PIN) was removed for histological evaluation. Results Rats in the crush group recovered toe spread between 5 and 8 days after surgery. Rats with nerve transfers demonstrated electrophysiological and histological findings of nerve regeneration but no behavioral recovery. Conclusions Ulnar nerve axons regrew into the superficial radial nerve and then into the PIN to reinnervate the extensor digitorum communis. We were unable to demonstrate behavioral recovery because rats cannot readapt to cross-nerve transfer.

Acupuncture on “Huantiao” (GB30) and "Yanglingquan" (GB34) acupoints promotes nerve regeneration in mice model of peripheral nerve injury

ObjectiveTo investigate the effects of acupuncture on promoting nerve regeneration in mice with sciatic nerve crushed injury, an animal model of peripheral nerve injury (PNI). MethodsAcupuncture was performed on the "Huantiao" (GB30) and "Yanglingquan" (GB34) acupoints in PNI mice model for 2 weeks. Gait analysis, toe spreading test, electrophysiological test, toluidine blue staining and immunostaining of myelin basic protein (MBP), neurofilament-200 (NF200), p75 neurotrophin receptor (p75NTR), and growth associated protein-43 (GAP43) were respectively performed to investigate the effects of acupuncture on crushed sciatic nerve. ResultsAcupuncture stimulation of “Huantiao” (GB30) and "Yanglingquan" (GB34) acupoints promoted the recovery of motor function and electrophysiological function in PNI mice model, which was indicated by a better gait level, toe spreading level and CMAP value in acupuncture group. The number of myelinated nerve fibers and the fluorescence intensity of MBP, NF200, p75NTR and GAP43 staining demonstrated that the acupuncture stimulation promoted the regeneration of injured nerves in PNI mice model. ConclusionAcupuncture significantly promoted the functional and morphological recovery of crushed sciatic nerve via promoting the expression of p75NTR in Schwann cells.

Influence of the Combination of Single Fascicle Grafting and Vascular Epithelial Growth Factor on the Nerve Reconstruction in the Rat Sciatic Nerve Injury Model: Experimental Study

Background and Aim: The purpose of this study was to evaluate the regeneration effects after sciatic nerve reconstruction with single fascicle grafting + vascular endothelial growth factor (VEGF) compared with traditional epineural suture. Methods: Sixty-four Wistar rats were divided into 2 groups randomly and created 10-25 mm sciatic nerve defects. In control group, nerve was reconstructed using traditional epineural suture and the rats of the study group were treated with single fascicle grafting + VEGF. At the point of 6 and 12 weeks, testing consisted of sciatic nerve function index (SFI), gastrocnemius muscle weight, toe spread test, pin-prick test was undergone. Results: The rats of 25mm defect subgroup repaired with single fascicle grafting + VEGF demonstrated significantly higher SFI score, toe spread test score, re- innervated muscle weight at the points of 6, 12 weeks. And in the 20, 25 mm defect rats of study group, pin-prick test score were significantly higher than the control group. Conclusion: Single fascicle grafting + VEGF was better to reconstruct long nerve defect compared to epineural suture.

Multilevel dynamic adjustments of geckos (Hemidactylus frenatus) climbing vertically: head-up versus head-down.

Many climbing animals use direction-dependent adhesives to attach to vertical or inclined surfaces. These structures adhere when activated via a pull but detach when pushed. Therefore, a challenge arises when a change in climbing direction causes external forces such as gravity to change its acting orientation upon the lizard. To investigate how specialized climbers adjust, we studied kinematics and dynamics of six Hemidactylus frenatus geckos climbing head-up and head-down a vertical racetrack. We found that limbs functionally swap their adhesive role: feet above the centre of mass (COM) generated adhesive forces, feet below the COM compressive forces, both equal in magnitude across directions. To investigate how lizards perform this swap, despite the constraint of their direction-dependent adhesives, we analysed kinematic adjustments across multiple smaller levels of hierarchy: limbs, feet and toes. All levels contributed: the hindfoot angle was reoriented realigning the adhesive structure, the hindlimb centre range of motion was further protracted and the hindfoot toe spreading was reduced. Notably, all three variables were adjustments of hindlimbs, suggesting that they make a more flexible contribution in upward versus downward climbing, while forelimbs may be anatomically or functionally constrained. The relevance of multilevel dynamic adjustments might inform the development of performant gaits for legged climbing robots.

Focal Application of Neurotrophic Factors Augments Outcomes of Nerve-Muscle-Endplate Grafting Technique for Limb Muscle Reinnervation.

We have developed a novel muscle reinnervation technique called "nerve-muscle-endplate grafting (NMEG) in the native motor zone (NMZ)." This study aimed to augment the outcomes of the NMEG-NMZ (NN) by focal application of exogenous neurotrophic factors (ENFs) for limb reinnervation. Adult rats were used to conduct NN plus ENF (NN/ENF) and autologous nerve grafting (ANG, technique control). The nerve innervating the left tibialis anterior (TA) muscle was resected and the denervated TA was immediately treated with NN/ENF or ANG. For NN procedure, an NMEG pedicle was taken from the lateral gastrocnemius muscle and transferred to the NMZ of the denervated TA. For ANG, the nerve gap was bridged with sural nerve. Three months after treatment, the extent of functional and neuromuscular recovery was assessed by measuring static toe spread, maximal muscle force, wet muscle weight, regenerated axons, and innervated motor endplates (MEPs). NN/ENF resulted in 90% muscle force recovery of the treated TA, which is far superior to ANG (46%) and NN alone (79%) as reported elsewhere. Toe spread recovered up to 89 and 49% of the control for the NN/ENF and ANG groups, respectively. The average wet muscle weight was 87 and 52% of the control for muscles treated with NN/ENF and ANG, respectively. The mean number of the regenerated axons was 88% of the control for the muscles treated with NN/ENF, which was significantly larger than that for the ANG-repaired muscles (39%). The average percentage of the innervated MEPs in the NN/ENF-treated TA (89%) was higher compared with that in the ANG-repaired TA (48%). ENF enhances nerve regeneration and MEP reinnervation that further augment outcomes of NN. The NN technique could be an alternative option to treat denervated or paralyzed limb muscles caused by traumatic nerve injuries or lesions.

Reinnervation of Paralyzed Limb Muscle by Nerve-Muscle-Endplate Grafting Technique.

We have developed a novel reinnervation technique called nerve-muscle-endplate grafting in the native motor zone (NMEG-NMZ). However, it remains unknown whether the NMEG-NMZ is effective for limb reinnervation. To evaluate the efficacy of the NMEG-NMZ in limb muscle reinnervation. Forty-five adult rats were divided into 3 groups: NMEG, end-to-end anastomosis (EEA, technique control), and denervation control (DC). The left tibialis anterior muscle was denervated by resecting its nerve. For NMEG-NMZ, the denervated tibialis anterior was reinnervated by transferring a NMEG pedicle from the lateral gastrocnemius muscle. Three months after surgery, static toe spread analysis was performed for all rats and muscle force was measured for the rats treated with NMEG and EEA. Muscle weight, myofiber morphology, regenerated axons, and reinnervated motor endplates in the treated muscles were also quantified and compared with those in the DC group. NMEG-NMZ technique resulted in better muscle force recovery (79% of the control) compared with EEA (51% of the control, P = .048). Toe spread analysis in NMEG-NMZ reinnervated muscles showed static sciatic index = -16.8, whereas -41.4 in EEA, P < .0001). The average weight of the NMEG-NMZ reinnervated muscles (86%) was greater than those of the EEA treated (71%) and DC (26%) muscles (all P < .0001). The mean count of the regenerated axons in the muscles with NMEG-NMZ was 76% of the control, which was larger than that in the muscles with EEA (46%), P < .0001. NMEG-NMZ technique has unique advantages and is superior to EEA for muscle reinnervation and functional recovery.

Is Popularity of Fibrin Glue a Misrepresentation? A Comparative Study with Fibrin Glue and Suture Anastomosis in Rat Sciatic Nerve Injury Analysing Functional, Histological, Electrophysiological Parameters.

Fibrin glue as an adjunct in peripheral nerve injuries has gained recent popularity. Whether fibrosis and inflammatory processes which are the major hindrances in repair reduce with fibrin glue has more of theoretical support than experimental. A prospective nerve repair study was conducted between two different species of rats as donor and recipient. Four comparison groups with 40 rats were outlined with or without fibrin glue in immediate post-injury period with fresh or cold preserved grafts were examined based on histological, macroscopic, functional, and electrophysiological criteria. There was suture site granuloma along with neuroma formation and inflammatory reaction and severe epineural inflammation in allografts with immediate suturing (Group A), whereas suture site inflammation and epineural inflammation were negligible in cold preserved allografts with immediate suturing (Group B). Allografts with minimal suturing and glue (Group C) had less severe epineural inflammation with less severe suture site granuloma and neuroma formation as compared to first two groups. Continuity of nerve was partial in later group as compared to other two. In fibrin glue only group (Group D), suture site granuloma and neuroma were absent, with negligible epineural inflammation, but continuity nerve was partial to absent in most of the rats with some showing partial continuity. Functionally, microsuturing with or without glue demonstrated significant difference with better SLR and toe spread (p = 0.042) as compared with only glue. Electrophysiologically, NCV was maximum in Group A and least in Group D at 12 weeks. We report significant difference in CMAP and NCV between microsuturing group vs. only glue group (p < 0.05) and also between microsuturing with glue group vs. only glue group (p < 0.05). There may be more data required with proper standardization for adept usage of fibrin glue. Though our results have shown partial success, it nonetheless highlights the lack of sufficient data for widespread glue usage.

Time-course gait pattern analysis in a rat model of foot drop induced by ventral root avulsion injury.

Foot drop is a common clinical gait impairment characterized by the inability to raise the foot or toes during walking due to the weakness of the dorsiflexors of the foot. Lumbar spine disorders are common neurogenic causes of foot drop. The accurate prognosis and treatment protocols of foot drop are not well delineated in the scientific literature due to the heterogeneity of the underlying lumbar spine disorders, different severities, and distinct definitions of the disease. For translational purposes, the use of animal disease models could be the best way to investigate the pathogenesis of foot drop and help develop effective therapeutic strategies for foot drops. However, no relevant and reproducible foot drop animal models with a suitable gait analysis method were developed for the observation of foot drop symptoms. Therefore, the present study aimed to develop a ventral root avulsion (VRA)-induced foot drop rat model and record detailed time-course changes of gait pattern following L5, L6, or L5 + L6 VRA surgery. Our results suggested that L5 + L6 VRA rats exhibited changes in gait patterns, as compared to sham lesion rats, including a significant reduction of walking speed, step length, toe spread, and swing phase time, as well as an increased duration of the stance phase time. The ankle kinematic data exhibited that the ankle joint angle increased during the mid-swing stage, indicating a significant foot drop pattern during locomotion. Time-course observations displayed that these gait impairments occurred as early as the first-day post-lesion and gradually recovered 7-14 days post-injury. We conclude that the proposed foot drop rat model with a video-based gait analysis approach can precisely detect the foot drop pattern induced by VRA in rats, which can provide insight into the compensatory changes and recovery in gait patterns and might be useful for serving as a translational platform bridging human and animal studies for developing novel therapeutic strategies for foot drop.

Effects of 4Weeks of High-Definition Transcranial Direct Stimulation and Foot Core Exercise on Foot Sensorimotor Function and Postural Control.

Objective: This study aimed to examine the effects of 4 weeks of high-definition transcranial direct current stimulation (HD-tDCS) and foot core exercise (FCE) on foot sensorimotor function (i.e., toe flexor strength and passive ankle kinesthesia) and postural control. Methods: In total, 36 participants were randomly assigned into three groups as follows: HD-tDCS, FCE, and the control group. A total of 12 training sessions were performed over 4 weeks (i.e., three sessions per week) in the laboratory. The HD-tDCS group received 20-min HD-tDCS with a current density of 2 mA, and the FCE group completed short foot exercise, towel curls, toe spread and squeeze, and balance board training. Participants in the control group just maintained the activities what they usually did and did not receive any interventions. Foot muscle strength, passive ankle kinesthesia, and postural control were assessed at baseline and post-intervention. Results: HD-tDCS induced a greater decrease in the percentage changes in the passive kinesthesia thresholds of ankle inversion (p < 0.001) and eversion (p = 0.013) than the control group. Compared with the control group, a significant increase in the percentage change in the metatarsophalangeal joint flexor strength was found in the HD-tDCS group (p = 0.008) and the FCE group (p = 0.027), and a significant increase in the percentage change in toe flexor strength was observed in the FCE group (p = 0.015). Moreover, FCE induced a greater reduction in the percent changes in the medial–lateral average center of gravity sway velocity in one-leg standing with eyes open (p = 0.033) and the anteroposterior average center of gravity sway velocity in one-leg standing with eyes closed (p < 0.001) than control. Conclusion: This study demonstrated that 4 weeks of HD-tDCS and FCE induced distinct benefits on foot sensorimotor function and the standing postural control performance in healthy young adults. HD-tDCS could improve the metatarsophalangeal joint flexor strength and the passive kinesthesia thresholds of ankle inversion and eversion. Meanwhile, FCE could also enhance foot muscle strength and enhance postural control performance in one-leg standing.

Amiodarone Provides Long-Lasting Local Anesthesia and Analgesia in Open-State Mouse Nociceptors.

Local anesthetics with long-lasting effects and selectivity for nociceptors have been sought over the past decades. In this study, we investigated whether amiodarone, a multiple channel blocker, provides long-lasting local anesthesia and whether adding a TRPV1 channel activator selectively prolongs sensory anesthetic effects without prolonging motor blockade. Additionally, we examined whether amiodarone provides long-lasting analgesic effects against inflammatory pain without TRPV1 channel activator co-administration. In the sciatic nerve block model, 32 adult C57BL/6J mice received either bupivacaine, amiodarone with or without capsaicin (a TRPV1 agonist), or vehicle via peri-sciatic nerve injection. Sensory and motor blockade were assessed either by pinprick and toe spread tests, respectively. In another set of 16 mice, inflammatory pain was induced in the hind paw by zymosan injection, followed by administration of either amiodarone or vehicle. Mechanical and thermal sensitivity and paw thickness were assessed using the von Frey and Hargreaves tests, respectively. The possible cardiovascular and neurological side effects of local amiodarone injection were assessed in another set of 12 mice. In the sciatic nerve block model, amiodarone produced robust anesthesia, and the co-administration of TRPV1 agonist capsaicin prolonged the duration of sensory blockade, but not that of motor blockade [complete sensory block duration: 195.0 ± 9.8 min vs. 28.8 ± 1.3 min, F (2, 21) = 317.6, p < 0.01, complete motor block duration: 27.5 ± 1.6 min vs. 21.3 ± 2.3 min, F (2, 22) = 11.1, p = 0.0695]. In the zymosan-induced inflammatory pain model, low-dose amiodarone was effective in reversing the mechanical and thermal hypersensitivity not requiring capsaicin co-administration [50% withdrawal threshold at 8 h (g): 0.85 ± 0.09 vs. 0.25 ± 0.08, p < 0.01, withdrawal latency at 4 h (s) 8.5 ± 0.5 vs. 5.7 ± 1.4, p < 0.05]. Low-dose amiodarone did not affect zymosan-induced paw inflammation. Local amiodarone did not cause cardiovascular or central nervous system side effects. Amiodarone may have the potential to be a long-acting and nociceptor-selective local anesthetic and analgesic method acting over open-state large-pore channels.

Efficacy of Hallux Valgus Deformity Correction Exercise Program in Young Females

&lt;p&gt;&lt;strong&gt;Background:&lt;/strong&gt; Hallux valgus deformity mostly seen in females because of high heels and tight/narrow shoes. Previous studies have focused on surgical treatment, orthosis, footwear modifications and tapping, but this not correct valgus deformity and causes certain complications. No studies are conducted showing proper exercise program effective in decreasing the valgus angle. The purpose of this study was to determine the efficacy of hallux valgus deformity correction exercise program in young females. &lt;strong&gt;Objectives:&lt;/strong&gt; To determine the efficacy of hallux valgus deformity correction exercise program in young females. Methods: 24 female subjects with mild and moderate hallux valgus angle were divided, in group A (experimental) treated with deformity correction exercises, mobilization, stretching and group B (control) with toe spread out and short foot exercises. A goniometer was used to determine the valgus angle of great toe. Visual analogue scale for the pain and functional limitations was evaluated by using Foot and Ankle Disability Index. &lt;strong&gt;Results:&lt;/strong&gt; On comparing both groups, there was no statistically significant difference seen in pre interventional values. In post interventional values, there was significant difference seen with p value for pain at rest (&amp;lt;0.0001) and on activity (&amp;lt;0.0001), goniometric range of motion of great toe of right (&amp;lt;0.0002) and left side (&amp;lt;0.0003), foot and ankle disability index score (&amp;lt;0.0238). &lt;strong&gt;Conclusion:&lt;/strong&gt; The conducted study shows that deformity correction exercises, stretching and mobilization had more beneficial effects than toe spread out and short foot exercises for correcting the deformity.&lt;/p&gt;

The acute effect of the toe spread out exercise on abductor hallucis muscle activity and navicular height

The acute effect of the toe spread out exercise on abductor hallucis muscle activity and navicular height

Curcumin enhances the proliferation and myelinization of Schwann cells through Runx2 to repair sciatic nerve injury

BackgroundRUNX Family Transcription Factor 2 (Runx2) promotes neurite outgrowth after sciatic nerve injury, and Curcumin can promote the expression of Runx2. It is worthwhile to explore whether curcumin’s repair effect on sciatic nerve injury is related to Runx2. ObjectiveTo investigate the repair effect of curcumin on sciatic nerve injury and its possible mechanism. ResultsCurcumin improved the sciatic functional index (SFI) and toe spread index (TSI) of rats with sciatic nerve injury and increased the number and diameter of myelinated axons in the sciatic nerve. Curcumin promoted the myelination of SCs (Schwann cells) by increasing the expression of peripheral myelin protein 22 (PMP22), fibrin, S100, and proliferating cell nuclear antige (PCNA). Curcumin treatment increased the proliferation of SCs and the expression of Runx2. Cell experiments further confirmed that curcumin promoted Schwann cell proliferation and myelination through Runx2. ConclusionCurcumin promotes SCs proliferation and myelination through Runx2 and improves sciatic nerve repair.