An analysis of differential gene expression in peripheral nerve and muscle utilizing RNA sequencing after polyethylene glycol nerve fusion in a rat sciatic nerve injury model.

Application of polyethylene glycol (PEG) to a peripheral nerve injury at the time of primary neurorrhaphy is thought to prevent Wallerian degeneration via direct axolemma fusion. The molecular mechanisms of nerve fusion and recovery are unclear. Our study tested the hypothesis that PEG alters gene expression in neural and muscular environments as part of its restorative properties. Lewis rats underwent unilateral sciatic nerve transection with immediate primary repair. Subjects were randomly assigned to receive either PEG treatment or standard repair at the time of neurorrhaphy. Samples of sciatic nerve distal to the injury and tibialis muscle at the site of innervation were harvested at 24 hours and 4 weeks postoperatively. Total RNA sequencing and subsequent bioinformatics analyses were used to identify significant differences in differentially expressed genes (DEGs) and their related biological pathways (p<0.05) in PEG-treated subjects compared to non-PEG controls. No significant DEGs were identified in PEG-treated sciatic nerve compared to controls after 24 hours, but 1,480 DEGs were identified in PEG-treated tibialis compared to controls. At 4 weeks, 918 DEGs were identified in PEG-treated sciatic nerve, whereas only 3 DEGs remained in PEG-treated tibialis compared to controls. DEGs in sciatic were mostly upregulated (79%) and enriched in pathways present during nervous system development and growth, whereas DEGs in muscle were mostly downregulated (77%) and related to inflammation and tissue repair. Our findings indicate that PEG application during primary neurorrhaphy leads to significant differential gene regulation in the neural and muscular environment that is associated with improved functional recovery in animals treated with PEG compared to sham non-PEG controls. A detailed understanding of key molecules underlying PEG function in recovery after peripheral nerve repair may facilitate amplification of PEG effects through systemic or focal treatments at the time of neurotmesis.

Targeted muscle reinnervation at the time of amputation to prevent the development of neuropathic pain.

INTRODUCTION: Targeted muscle reinnervation (TMR) is an established modality for the surgical management of neuropathic pain. Although the preventive effect of primary (acute) TMR at the time of amputation has been demonstrated previously, it remains unclear how many and which patients benefit most. Therefore, this study investigated the proportion of patients achieving sustained pain prophylaxis following amputation, as well as factors associated with its efficacy. METHODS: Primary patients who underwent TMR with a minimum follow-up of 6 months between 2018 and 2023 were enrolled. Pain outcomes (numeric rating scale [NRS], 0-10), comorbidities, and surgical factors were collected from chart review. Patients achieving sustained pain prophylaxis (NRS of ≤3 for ≥3 months until final follow-up) were identified. Multilevel mixed-effect models and multivariable regression were used to visualize pain courses and identify associated factors. RESULTS: Seventy-five patients who underwent primary TMR were included (median follow-up: 2.0 years), of whom 57.3% achieved sustained pain prophylaxis whereas 26.7% reported pain disappearance. Distal amputation levels (p = 0.036), a lower Elixhauser Comorbidity Index (p = 0.001), and the absence of psychiatric comorbidities (p = 0.039) were associated with pain prophylaxis. CONCLUSION: This study demonstrates that more than half of all patients undergoing primary TMR achieved sustained pain prophylaxis, and approximately a quarter of patients achieved sustained pain disappearance. Several factors associated with these favorable outcomes are described. These results will aid in preoperative counseling, managing patient expectations, and selecting patients who may benefit most from primary TMR surgery. LEVEL OF EVIDENCE: IV - Therapeutic.

Current and Future Directions for Upper Extremity Amputations: Comparisons Between Regenerative Peripheral Nerve Interface and Targeted Muscle Reinnervation Surgeries.

Upper extremity amputation can lead to significant functional morbidity. The main goals after amputation are to minimize pain and maintain or improve functional status while optimizing the quality of life. Postamputation pain is common and can be addressed with regenerative peripheral nerve interface surgery or targeted muscle reinnervation surgery. Both modalities are effective in treating residual limb pain and phantom limb pain, as well as improving prosthetic use. Differences in surgical technique between the 2 approaches need to be weighed when deciding what strategy may be most appropriate for the patient.

[Applied anatomy study and preliminary clinical application of hyper selective neurectomy of triceps branches combined with partial neurotomy of S 2 nerve root to relieve spastic equinus foot].

Objective: To observe the possibility of hyper selective neurectomy (HSN) of triceps branches combined with partial neurotomy of S 2 nerve root for relieving spastic equinus foot. Methods: Anatomical studies were performed on 12 adult cadaveric specimens. The S 2 nerve root and its branches were exposed through the posterior approach. Located the site where S 2 joined the sciatic nerve and measured the distance to the median line and the vertical distance to the posterior superior iliac spine plane, and the S 2 nerve root here was confirmed to have given off branches of the pelvic splanchnic nerve, the pudendal nerve, and the posterior femoral cutaneous nerve. Between February 2023 and November 2023, 4 patients with spastic equinus foot were treated with HSN of muscle branches of soleus, gastrocnemius medial head and lateral head, and cut the branch where S 2 joined the sciatic nerve. There were 3 males and 1 female, the age ranged from 5 to 46 years, with a median of 26 years. The causes included traumatic brain injury in 2 cases, cerebral hemorrhage in 1 case, and cerebral palsy in 1 case. The disease duration ranged from 15 to 84 months, with a median of 40 months. The triceps muscle tone measured by modified Ashworth scale (MAC) before operation was grade 3 in 2 cases and grade 4 in 2 cases. The muscle strength measured by Daniels-Worthingham manual muscle test (MMT) was grade 2 in 1 case, grade 3 in 1 case, and 2 cases could not be accurately measured due to grade 4 muscle tone. The Holden walking function grading was used to evaluate lower limb function and all 4 patients were grade 2. After operation, triceps muscle tone, muscle strength, and lower limb function were evaluated by the above grading. Results: The distance between the location where S 2 joined the sciatic nerve and median line was (5.71±0.53) cm and the vertical distance between the location and posterior superior iliac spine plane was (6.66±0.86) cm. Before joining the sciatic nerve, the S 2 nerve root had given off branches of the pelvic splanchnic nerve, the pudendal nerve, and the posterior femoral cutaneous nerve. All the 4 patients successfully completed the operation, and the follow-up time was 4-13 months, with a median of 7.5 months. At last follow-up, the muscle tone of the patients decreased by 2-3 grades when compared with that before operation, and the muscle strength did not decrease when compared with that before operation. Holden walking function grading improved by 1-2 grades, and there was no postoperative hypoesthesia in the lower limbs. Conclusion: HSN of triceps branches combined with partial neurotomy of S 2 nerve root can relieve spastic equinus foot without damaging other sacral plexus nerves.

Anatomy of the Achilles tendon-A pictorial review.

The Achilles tendon (AT) is the strongest tendon of the human body. The knowledge of AT anatomy is a basic prerequisite for the successful treatment of acute and chronic lesions. The structure of the AT results from a complicated fusion of three parts: the tendons of the medial and lateral gastrocnemius and the soleus muscles. From proximal to distal, the tendon fibers twist in a long spiral into a roughly 90° internal rotation. The tendon is narrowest approximately 5-7 cm above its calcaneal insertion and from there it expands again. The topography of the footprints of the individual AT components reflects the tendon origins. The anterior (deep) AT fibers insert into the middle third of the posterior aspect of the calcaneal tuberosity, the posterior (superficial) fibers pass over the calcaneal tuberosity and fuse with the plantar aponeurosis. A deep calcaneal bursa is interposed between the calcaneal tuberosity and the AT anterior surface. The AT has no synovial sheath but is covered along its entire length with a sliding connective tissue, the paratenon which is, however, absent on its anterior surface. The AT is supplied by the posterior tibial artery (PTA) and the peroneal artery (PA). Motor innervation of the triceps surae muscle is provided by fibers of the tibial nerve which also gives off sensitive fibers for the AT. Sensitive innervation is also provided via the sural nerve. The sural nerve crosses the AT approximately 11 cm proximal to the calcaneal tuberosity. The forces acting on the AT during exercise may be up to 12 times the body weight. Physiological stretching of AT collagen fibers ranges between 2% and 4% of its length. Stretching of the tendon over 4% results in microscopic failure and stretching beyond 8% in macroscopic failure.

All-in-one wearable drug efficacy assessment systems for bulbar muscle function using amyotrophic lateral sclerosis animal models.

Preclinical studies are crucial for developing amyotrophic lateral sclerosis drugs. Current FDA-approved drugs have been created by monitoring limb muscle function and histological analysis of amyotrophic lateral sclerosis model animals. Drug candidates for this disease have yet to be tested for bulbar-onset type due to the limitations of traditional preclinical tools: excessive animal use and discrete detection of disease progress. Here, our study introduces an all-in-one, wireless, integrated wearable system for facilitating continuous drug efficacy assessment of dysphagia-related muscles in animals during natural eating behaviors. By incorporating a kirigami-based strain-isolation mechanism, this device mounted on the skin of animals mitigates electromyography signal contamination caused by unpredictable animal movements. Our findings indicate this system, measuring the progression of motor neuron denervation, offers high precision in monitoring drug effects on dysphagia-responsible bulbar muscles. This study paves the way for more humane and efficient approaches to developing treatment solutions for degenerative neuromuscular diseases.

The accessory brachioradialis muscle: prevalence of a rare variant with possible clinical implications.

PURPOSE: The brachioradialis muscle (BRM) belongs to the lateral group of forearm muscles and contributes to the elbow flexion. Accessory brachioradialis muscle (ABRM) or "brachioradialis accessorius" represents an uncommon BRM variant, not been enough studied. The present study investigates the prevalence of the ABRM, along with its origin, insertion, and innervation. MATERIALS: Eighty-three upper limbs were meticulously dissected at the arm, forearm, and cubital fossa to investigate the ABRM presence. When the variant muscle was identified, morphometric measurements were obtained. RESULTS: The ABRM was identified in two upper limbs (2/83, 2.4%), in a male cadaver, bilaterally. Its origin was located along with the typical BRM, and its insertion was identified into the anterior surface of the radius (proximal third). The ABRM was innervated by the radial nerve, coursing posteriorly (deeply). CONCLUSIONS: In the current study, the variant muscle was observed in 2.4%. Radial nerve compression, at the forearm, is not an uncommon entrapment neuropathy. The relationship between the radial nerve and the ABRM could precipitate radial neuropathy.

Voluntary co-contraction of ankle muscles alters motor unit discharge characteristics and reduces estimates of persistent inward currents.

Motoneuronal persistent inward currents (PICs) are facilitated by neuromodulatory inputs but are highly sensitive to local inhibitory circuits. Estimates of PICs are reduced by group Ia reciprocal inhibition, and increased with the diffuse actions of neuromodulators released during remote muscle contraction. However, it remains unknown how motoneurons function in the presence of simultaneous excitatory and inhibitory commands. To probe this topic, we investigated motor unit discharge patterns and estimated PICs during voluntary co-contraction of ankle muscles, which simultaneously demands the contraction of agonist-antagonist pairs. Twenty participants performed triangular ramps of both co-contraction (simultaneous dorsiflexion and plantar flexion) and isometric dorsiflexion to a peak of 30% of their maximum muscle activity from a maximal voluntary contraction. Motor unit spike trains were decomposed from high-density surface EMG activity recorded from tibialis anterior using blind source separation algorithms. Voluntary co-contraction altered motor unit discharge rate characteristics. Discharge rate at recruitment and peak discharge rate were modestly reduced (∼6% change; P < 0.001; d = 0.22) and increased (∼2% change; P = 0.001, d = -0.19), respectively, in the entire dataset but no changes were observed when motor units were tracked across conditions. The largest effects during co-contraction were that estimates of PICs (ΔF) were reduced by ∼20% (4.47 vs. 5.57 pulses per second during isometric dorsiflexion; P < 0.001, d = 0.641). These findings suggest that, during voluntary co-contraction, the inhibitory input from the antagonist muscle overcomes the additional excitatory and neuromodulatory drive that may occur due to the co-contraction of the antagonist muscle, which constrains PIC behaviour. KEY POINTS: Voluntary co-contraction is a unique motor behaviour that concurrently provides excitatory and inhibitory synaptic input to motoneurons. Co-contraction of agonist-antagonist pairs alters agonist motor unit discharge characteristics, consistent with reductions in persistent inward current magnitude.

Targeted Muscle Reinnervation for a Symptomatic Neuroma in a Traumatic Transmetatarsal Amputee: A Case Report.

CASE: An overall healthy 48-year-old man suffered a left foot mangled crush injury resulting in a post-transmetatarsal amputation and subsequently developing a painful neuroma on the plantar surface of the foot. To avoid the zone of injury, targeted muscle reinnervation was used to treat the neuroma by coapting the tibial nerve to the motor point of the flexor hallucis longus (FHL) muscle. At 1-year follow-up, the patient reported no pain at rest, returned to work, and could ambulate with an orthosis for 30 minutes. CONCLUSION: Rare tibial nerve coaptations to the FHL could serve as a treatment option for patients with neuromas in traumatic postmetatarsal amputation.

Activation of skeletal muscle mechanoreceptors and nociceptors reduces the exercise performance of the contralateral homologous muscles.

Increasing evidence suggests that activation of muscle nerve afferents may inhibit central motor drive, affecting contractile performance of remote exercising muscles. Although these effects are well documented for metaboreceptors, very little is known about the activation of mechano- and mechanonociceptive afferents on performance fatigability. Therefore, the purpose of the present study was to examine the influence of mechanoreceptors and nociceptors on performance fatigability. Eight healthy young males undertook four randomized experimental sessions on separate occasions in which the experimental knee extensors were the following: 1) resting (CTRL), 2) passively stretched (ST), 3) resting with delayed onset muscle soreness (DOMS), or 4) passively stretched with DOMS (DOMS+ST), whereas the contralateral leg performed an isometric time to task failure (TTF). Changes in maximal voluntary contraction (ΔMVC), potentiated twitch force (ΔQtw,pot), and voluntary muscle activation (ΔVA) were also assessed. TTF was reduced in DOMS+ST (-43%) and ST (-29%) compared with CTRL. DOMS+ST also showed a greater reduction of VA (-25% vs. -8%, respectively) and MVC compared with CTRL (-28% vs. -45%, respectively). Rate of perceived exertion (RPE) was significantly increased at the initial stages (20-40-60%) of the TTF in DOMS+ST compared with all conditions. These findings indicate that activation of mechanosensitive and mechanonociceptive afferents of a muscle with DOMS reduces TTF of the contralateral homologous exercising limb, in part, by reducing VA, thereby accelerating mechanisms of central fatigue.NEW & NOTEWORTHY We found that activation of mechanosensitive and nociceptive nerve afferents of a rested muscle group experiencing delayed onset muscle soreness was associated with reduced exercise performance of the homologous exercising muscles of the contralateral limb. This occurred with lower muscle voluntary activation of the exercising muscle at the point of task failure.

Unusual branch of the saphenous nerve to the sartorius muscle in a female cadaver.

PURPOSE: The saphenous nerve is a predominantly sensory nerve. It is the longest nerve of the body which supplies the skin of the medial side of the leg and foot as far as the ball of the great toe. We present here an unusual motor branch of the saphenous nerve to the sartorius muscle. METHOD: Institutional guidelines for use of human cadaver were followed. Routine dissection of the lower limbs for undergraduate medical teaching was performed in a 67 years old female cadaver employing standard methods. Relevant gross features of the variations were photographed. H&E staining of relevant structure was done and photomicrographed. RESULTS: The unusual motor branch to Sartorius was observed in the right thigh. The branch was given off in the lower third of the thigh after the saphenous nerve exited the adductor canal. The branch was distinctly seen entering the substance of the sartorius. The structure was confirmed to be a peripheral nerve by histological examination. The saphenous nerve then descended between the sartorius and gracilis tendons, pierced the fascia lata and became cutaneous. CONCLUSION: The motor branch to the sartorius muscle is a very rare branch whose knowledge is important for clinicians as it can get damaged during arthroscopy and other knee surgery or during adductor canal block.

Diagnosis of suprascapular nerve entrapment syndrome based on the infraspinatus muscle cross-sectional area on shoulder MRI.

Suprascapular nerve entrapment (SNE) syndrome is a commonly overlooked cause of shoulder weakness and pain. It frequently causes weakness over the posterior and lateral and posterior aspects of the shoulder, as well as pain of infraspinatus muscles. Therefore, we considered that the infraspinatus muscle cross-sectional area (IMCSA) might be a new morphological parameter to analyze SNE syndrome. We assumed that the IMCSA is an important morphologic parameter in SNE syndrome diagnosis. We acquired infraspinatus muscle data from 10 patients with SNE syndrome and from 10 healthy subjects who had undergone magnetic resonance imaging of the shoulder and who revealed no evidence of SNE syndrome. We analyzed the infraspinatus muscle thickness (IMT) and IMCSA at the shoulder on the imaging of the shoulder using our image analysis program. The IMCSA was measured as the whole infraspinatus muscle cross-sectional area that was most atrophied in the sagittal S-MR images. The IMT was measured as the thickest level of infraspinatus muscle. The mean IMT was 29.17 ±â€…2.81 mm in the healthy subjects and 25.22 ±â€…3.19 mm in the SNE syndrome group. The mean IMCSA was 1321.95 ±â€…175.91 mm2 in the healthy group and 1048.38 ±â€…259.94 mm2 in the SNE syndrome group. SNE syndrome patients had significantly lower IMT (P < .001) and IMCSA (P < .001) than the healthy group. The ROC curve shows that the optimal cutoff point of the IMT was 26.74 mm, with 70.0% sensitivity, 70.0% specificity, and an AUC of 0.83 (95% CI, 0.65-1.00). The best cutoff value of the IMCSA was 1151.02 mm2, with 80.0% sensitivity, 80.0% specificity, and AUC of 0.87 (95% CI, 0.69-1.00). The IMT and IMCSA were both significantly associated with SNE syndrome. And the IMCSA was a highly sensitive diagnostic tool.

Neuroplastic alterations in common synaptic inputs and synergistic motor unit clusters controlling the vastii muscles of individuals with ACL reconstruction.

This cross-sectional study aims to elucidate the neural mechanisms underlying the control of knee extension forces in individuals with anterior cruciate ligament reconstruction (ACLR). Eleven soccer players with ACLR and nine control players performed unilateral isometric knee extensions at 10% and 30% of their maximum voluntary force (MVF). Simultaneous recordings of high-density surface electromyography (HDEMG) and force output were conducted for each lower limb, and HDEMG data from the vastus lateralis (VL) and vastus medialis (VM) muscles were decomposed into individual motor unit spike trains. Force steadiness was estimated using the coefficient of variation of force. An intramuscular coherence analysis was adopted to estimate the common synaptic input (CSI) converging to each muscle. A factor analysis was applied to investigate the neural strategies underlying the control of synergistic motor neuron clusters, referred to as motor unit modes. Force steadiness was similar between lower limbs. However, motor neurons innervating the VL on the reconstructed side received a lower proportion of CSI at low-frequency bandwidths (<5 Hz) compared with the unaffected lower limbs (P < 0.01). Furthermore, the reconstructed side demonstrated a higher proportion of motor units associated with the neural input common to the synergistic muscle, as compared with the unaffected lower limbs (P < 0.01). These findings indicate that the VL muscle of reconstructed lower limbs contribute marginally to force steadiness and that a plastic rearrangement in synergistic clusters of motor units involved in the control of knee extension forces is evident following ACLR.NEW & NOTEWORTHY Chronic quadriceps dysfunction is common after anterior cruciate ligament reconstruction (ACLR). We investigated voluntary force control strategies by estimating common inputs to motor neurons innervating the vastii muscles. Our results showed attenuated common inputs to the vastus lateralis and plastic rearrangements in functional clusters of motor neurons modulating knee extension forces in the reconstructed limb. These findings suggest neuroplastic adjustments following ACLR that may occur to fine-tune the control of quadriceps forces.

Structural switch in acetylcholine receptors in developing muscle.

During development, motor neurons originating in the brainstem and spinal cord form elaborate synapses with skeletal muscle fibres1. These neurons release acetylcholine (ACh), which binds to nicotinic ACh receptors (AChRs) on the muscle, initiating contraction. Two types of AChR are present in developing muscle cells, and their differential expression serves as a hallmark of neuromuscular synapse maturation2-4. The structural principles underlying the switch from fetal to adult muscle receptors are unknown. Here, we present high-resolution structures of both fetal and adult muscle nicotinic AChRs, isolated from bovine skeletal muscle in developmental transition. These structures, obtained in the absence and presence of ACh, provide a structural context for understanding how fetal versus adult receptor isoforms are tuned for synapse development versus the all-or-none signalling required for high-fidelity skeletal muscle contraction. We find that ACh affinity differences are driven by binding site access, channel conductance is tuned by widespread surface electrostatics and open duration changes result from intrasubunit interactions and structural flexibility. The structures further reveal pathogenic mechanisms underlying congenital myasthenic syndromes.

Dystrophin S3059 phosphorylation partially attenuates denervation atrophy in mouse tibialis anterior muscles.

The dystrophin protein has well-characterized roles in force transmission and maintaining membrane integrity during muscle contraction. Studies have reported decreased expression of dystrophin in atrophying muscles during wasting conditions, and that restoration of dystrophin can attenuate atrophy, suggesting a role in maintaining muscle mass. Phosphorylation of S3059 within the cysteine-rich region of dystrophin enhances binding between dystrophin and ß-dystroglycan, and mimicking phosphorylation at this site by site-directed mutagenesis attenuates myotube atrophy in vitro. To determine whether dystrophin phosphorylation can attenuate muscle wasting in vivo, CRISPR-Cas9 was used to generate mice with whole body mutations of S3059 to either alanine (DmdS3059A) or glutamate (DmdS3059E), to mimic a loss of, or constitutive phosphorylation of S3059, on all endogenous dystrophin isoforms, respectively. Sciatic nerve transection was performed on these mice to determine whether phosphorylation of dystrophin S3059 could attenuate denervation atrophy. At 14 days post denervation, atrophy of tibialis anterior (TA) but not gastrocnemius or soleus muscles, was partially attenuated in DmdS3059E mice relative to WT mice. Attenuation of atrophy was associated with increased expression of ß-dystroglycan in TA muscles of DmdS3059E mice. Dystrophin S3059 phosphorylation can partially attenuate denervation-induced atrophy, but may have more significant impact in less severe modes of muscle wasting.

Central α2-adrenergic mechanisms regulate human sympathetic neuronal discharge strategies.

The present study investigated the impact of central α2-adrenergic mechanisms on sympathetic action potential (AP) discharge, recruitment and latency strategies. We used the microneurographic technique to record muscle sympathetic nerve activity and a continuous wavelet transform to investigate postganglionic sympathetic AP firing during a baseline condition and an infusion of a α2-adrenergic receptor agonist, dexmedetomidine (10 min loading infusion of 0.225 µg kg-1; maintenance infusion of 0.1-0.5 µg kg h-1) in eight healthy individuals (28 ± 7 years, five females). Dexmedetomidine reduced mean pressure (92 ± 7 to 80 ± 8 mmHg, P < 0.001) but did not alter heart rate (61 ± 13 to 60 ± 14 bpm; P = 0.748). Dexmedetomidine reduced sympathetic AP discharge (126 ± 73 to 27 ± 24 AP 100 beats-1, P = 0.003) most strongly for medium-sized APs (normalized cluster 2: 21 ± 10 to 5 ± 5 AP 100 beats-1; P < 0.001). Dexmedetomidine progressively de-recruited sympathetic APs beginning with the largest AP clusters (12 ± 3 to 7 ± 2 clusters, P = 0.002). Despite de-recruiting large AP clusters with shorter latencies, dexmedetomidine reduced AP latency across remaining clusters (1.18 ± 0.12 to 1.13 ± 0.13 s, P = 0.002). A subset of six participants performed a Valsalva manoeuvre (20 s, 40 mmHg) during baseline and the dexmedetomidine infusion. Compared to baseline, AP discharge (Δ 361 ± 292 to Δ 113 ± 155 AP 100 beats-1, P = 0.011) and AP cluster recruitment elicited by the Valsalva manoeuvre were lower during dexmedetomidine (Δ 2 ± 1 to Δ 0 ± 2 AP clusters, P = 0.041). The reduction in sympathetic AP latency elicited by the Valsalva manoeuvre was not affected by dexmedetomidine (Δ -0.09 ± 0.07 to Δ -0.07 ± 0.14 s, P = 0.606). Dexmedetomidine reduced baroreflex gain, most strongly for medium-sized APs (normalized cluster 2: -6.0 ± 5 to -1.6 ± 2 % mmHg-1; P = 0.008). These data suggest that α2-adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans. KEY POINTS: Sympathetic postganglionic neuronal subpopulations innervating the human circulation exhibit complex patterns of discharge, recruitment and latency. However, the central neural mechanisms governing sympathetic postganglionic discharge remain unclear. This microneurographic study investigated the impact of a dexmedetomidine infusion (α2-adrenergic receptor agonist) on muscle sympathetic postganglionic action potential (AP) discharge, recruitment and latency patterns. Dexmedetomidine infusion inhibited the recruitment of large and fast conducting sympathetic APs and attenuated the discharge of medium sized sympathetic APs that fired during resting conditions and the Valsalva manoeuvre. Dexmedetomidine infusion elicited shorter sympathetic AP latencies during resting conditions but did not affect the reductions in latency that occurred during the Valsalva manoeuvre. These data suggest that α2-adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans.

Continuous neural control of a bionic limb restores biomimetic gait after amputation.

For centuries scientists and technologists have sought artificial leg replacements that fully capture the versatility of their intact biological counterparts. However, biological gait requires coordinated volitional and reflexive motor control by complex afferent and efferent neural interplay, making its neuroprosthetic emulation challenging after limb amputation. Here we hypothesize that continuous neural control of a bionic limb can restore biomimetic gait after below-knee amputation when residual muscle afferents are augmented. To test this hypothesis, we present a neuroprosthetic interface consisting of surgically connected, agonist-antagonist muscles including muscle-sensing electrodes. In a cohort of seven leg amputees, the interface is shown to augment residual muscle afferents by 18% of biologically intact values. Compared with a matched amputee cohort without the afferent augmentation, the maximum neuroprosthetic walking speed is increased by 41%, enabling equivalent peak speeds to persons without leg amputation. Further, this level of afferent augmentation enables biomimetic adaptation to various walking speeds and real-world environments, including slopes, stairs and obstructed pathways. Our results suggest that even a small augmentation of residual muscle afferents restores biomimetic gait under continuous neuromodulation in individuals with leg amputation.

End-to-side neurorrhaphy in the reconstruction of peripheral segmental neural loss: an experimental study.

PURPOSE: To evaluate the effects on peripheral neural regeneration of the end-to-side embracing repair technique compared to the autograft repair technique in Wistar rats. METHODS: Fifteen male Wistar rats were divided into three groups with five animals each: denervated group (GD), autograft group (GA), and embracing group (EG). For the evaluation, the grasping test, electroneuromyography (ENMG), and muscle weight assessment were used. RESULTS: Muscle weight assessment and ENMG did not show significant neural regeneration at the end of 12 weeks in the DG and GE groups, but only in GA. The grasping test showed an increase in strength between the surgery and the fourth week in all groups, and only the GA maintained this trend until the 12th week. CONCLUSIONS: The present study indicates that the neural regeneration observed in the end-to-side embracing neurorrhaphy technique, in the repair of segmental neural loss, is inferior to autograft repair in Wistar rats.

Exploring the effect of the nerve conduction distance on the MScanFit method ofmotor unit number estimation (MUNE).

OBJECTIVE: MScanFit motor unit number estimation (MUNE) is a sensitive method for detecting motor unit loss and has demonstrated high reproducibility in various settings. In this study, our aim was to assess the outputs of this method when the nerve conduction distance is increased. METHODS: MScanFit recordings were obtained from the abductor digiti minimi muscle of 20 healthy volunteers. To evaluate the effect of nerve conduction distance, the ulnar nerve was stimulated from the wrist and elbow respectively. Reproducibility of MUNE, compound muscle action potential (CMAP), and other motor unit parameters were assessed using intraclass correlation coefficients (ICCs). RESULTS: Motor unit numbers obtained from stimulation at the wrist and elbow did not significantly differ and exhibited strong consistency in the ICC test (120.3 ± 23.7 vs. 118.5 ± 27.9, p > 0.05, ICC: 0.88). Similar repeatability values were noted for other parameters. However, the Largest Unit (%) displayed notable variability between the two regions and exhibited a negative correlation with nerve conduction distance. CONCLUSION: Our findings indicate that MScanFit can consistently calculate motor unit numbers and most of its outputs without substantial influence from nerve conduction distance. Exploring MScanFit's capabilities in various settings could enhance our understanding of its strengths and limitations for extensive use in clinical practice.

Actigraphy-based sleep and muscle sympathetic nerve activity in humans.

Short and insufficient sleep are prevalent and associated with cardiovascular disease, with the sympathetic nervous system as a suspected mediator. The purpose of the present study was to investigate the association between objective, actigraphy-based total sleep time (TST), sleep efficiency (SE), and cardiovascular and sympathetic regulation in healthy adults. We hypothesized that short TST and low SE would be associated with elevated resting blood pressure, heart rate (HR), and muscle sympathetic nerve activity (MSNA). Participants included 94 individuals [46 males, 48 females, age: 30 ± 15 yr, body mass index (BMI): 26 ± 4 kg/m2]. All participants underwent at least 7 days of at-home, wristwatch actigraphy monitoring (avg: 10 ± 3 days). Seated blood pressures were assessed using brachial blood pressure measurements, followed by a 10-minute supine autonomic testing session consisting of continuous HR (electrocardiogram), beat-by-beat blood pressure (finger plethysmograph), and MSNA (microneurography) monitoring. Partial correlations were used to determine the relationship between sleep and cardiovascular parameters while accounting for the influence of age, sex, and BMI. TST was not associated with MAP (R = -0.105, P = 0.321), HR (R = 0.093, P = 0.383), or MSNA burst frequency (BF; R = -0.168, P = 0.112) and burst incidence (BI; R = -0.162, P = 0.124). Similarly, SE was not associated with MAP (R = -0.088, P = 0.408), HR (R = -0.118, P = 0.263), MSNA BF (R = 0.038, P = 0.723), or MSNA BI (R = 0.079, P = 0.459). In contrast to recent preliminary findings, our results do not support a significant association between actigraphy-based sleep duration or efficiency and measures of resting blood pressure, heart rate, and MSNA.NEW & NOTEWORTHY The present study investigated the independent association between actigraphy-based sleep duration, efficiency, and measures of blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) in adult males and females. Contrary to our hypothesis, the findings do not support an independent association between habitual sleep and cardiovascular or sympathetic neural activity. However, these findings do not preclude a potential association between these parameters in populations with sleep disorders and/or cardiovascular disease.