This study investigated whether abnormal peak inversion spontaneous potentials (PISPs) recorded at resting myofascial trigger points (MTrPs) stem from the discharge of muscle spindles. Forty-eight male Sprague-Dawley rats were randomly divided into six groups. Five groups underwent MTrP modeling intervention, whereas one group did not receive intervention and was duly designated as the blank control. After model construction, five rat models were randomly subjected to ramp-and-hold stretch tests, succinylcholine injection, eperisone hydrochloride injection, saline injection, and blank drug intervention. By contrast, the rats in the blank control group were subjected to ramp-and-hold stretch tests as a control. Frequencies and amplitudes of PISPs were recorded pre- and post-interventions and compared with those of the blank group. Stretch tests showed that the depolarization time and amplitude of PISPs ranged from 0.4 ms to 0.9 ms and from 80 uV to 140 μV, respectively. However, no PISPs were observed in the control rats. The frequency of PISPs in the ramp and hold phases and the first second after the hold phase was higher than that before stretching (p < 0.01). Succinylcholine and eperisone exerted excitatory and inhibitory effects on PISPs, respectively. In the group injected with 0.9% saline, no considerable differences of the PISPs were observed during the entire observation period. In conclusion, PISPs recorded at resting MTrPs are closely related to muscle spindles. The formation of MTrPs may be an important factor that regulate dysfunctional muscle spindles.

The centre of the highest region of muscle spindle abundance (CHRMSA) in the intramuscular nerve-dense region has been suggested as the optimal target location for injecting botulinum toxin A to block muscle spasms. The anterior forearm muscles have a high incidence of spasticity. However, the CHRMSA in the intramuscular nerve-dense region of the forearm anterior muscle group has not been defined. This study aimed to accurately define the body surface position and the depth of CHRMSA in an intramuscular nerve-dense region of the anterior forearm muscles. Twenty-four adult cadavers (57.7 ± 11.5 years) were included in this study. The curved line close to the skin connecting the medial and lateral epicondyles of the humerus was designated as the horizontal reference line (H line), and the line connecting the medial epicondyle of the humerus and the ulnar styloid was defined as the longitudinal reference line (L line). Modified Sihler\'s staining, haematoxylin-eosin staining and computed tomography scanning were employed to determine the projection points (P and P\') of the CHRMSAs on the anterior and posterior surfaces of the forearm. The positions (PH and PL) of point P projected onto the H and L lines, and the depth of each CHRMSA, were determined using the Syngo system. The PH of the CHRMSA of the ulnar head of pronator teres, humeral head of pronator teres, flexor carpi radialis, palmaris longus, flexor carpi ulnaris, ulnar part of flexor digitorum superficialis, radial part of flexor digitorum superficialis, flexor pollicis longus, ulnar part of flexor digitorum profundus, radial portion of flexor digitorum profundus and pronator quadratus muscles were located at 42.48%, 45.52%, 41.20%, 19.70%, 7.77%, 25.65%, 47.42%, 53.47%, 12.28%, 38.41% and 51.68% of the H line, respectively; the PL were located at 18.38%, 12.54%, 28.83%, 13.43%, 17.65%, 32.76%, 57.32%, 64.12%, 20.05%, 45.94% and 88.71% of the L line, respectively; the puncture depths were located at 21.92%, 27.25%, 23.76%, 18.04%, 15.49%, 31.36%, 26.59%, 41.28%, 38.72%, 45.14% and 53.58% of the PP\' line, respectively. The percentage values are the means of individual values. We recommend that the body surface puncture position and depth of the CHRMSA are the preferred locations for the intramuscular injection of botulinum toxin A to block anterior forearm muscle spasms.

Proprioception is sensed by muscle spindles for precise locomotion and body posture. Unlike the neuromuscular junction (NMJ) for muscle contraction which has been well studied, mechanisms of spindle formation are not well understood. Here we show that sensory nerve terminals are disrupted by the mutation of Lrp4, a gene required for NMJ formation; inducible knockout of Lrp4 in adult mice impairs sensory synapses and movement coordination, suggesting that LRP4 is required for spindle formation and maintenance. LRP4 is critical to the expression of Egr3 during development; in adult mice, it interacts in trans with APP and APLP2 on sensory terminals. Finally, spindle sensory endings and function are impaired in aged mice, deficits that could be diminished by LRP4 expression. These observations uncovered LRP4 as an unexpected regulator of muscle spindle formation and maintenance in adult and aged animals and shed light on potential pathological mechanisms of abnormal muscle proprioception.

Muscle spindle is the key proprioceptor in skeletal muscles and plays important roles in many physiological activities, such as maintaining posture, regulating movement and controlling speed variation. It has significant clinical relevance and is emerging as a promising therapeutic target for the treatment of motor functional impairment and metabolic diseases. In this review, we summarized muscle spindle distribution and the mechanism of mechanical signal transmission, and reviewed the research progress on morphological and structural characteristics of muscle spindles.

Angiotensin-converting enzyme 2 (ACE2) is considered as an endogenous negative regulator of renin-angiotensin system (RAS), exerting multiple cardiovascular protective roles. Whether mechanical stretch modulates ACE2 expression remains unknown. The present study aimed at investigating whether ACE2 is involved in physiological stretch (10% elongation, 1 Hz) mediated cellular functions and the underlying mechanism. Cultured human aortic smooth muscle cells (HASMCs) were exposed to 10% stretch for indicated time, and real-time PCR and Western blot analysis showed 10% stretch increased ACE2 expression and activity significantly compared with static conditions and increased Ang-(1-7) level, but decreased Ang II level; Brdu incorporation assay and Scratch test showed that ACE2 was involved in the inhibition of HASMCs proliferation and migration by 10% stretch; the Dual-Luciferase Reporter Assay demonstrated that 10% increased ACE2 promoter activity, but had no effect on ACE2 mRNA stability; kinase inhibition study and Electrophoretic mobility shift assay (EMSA) showed that JNK1/2 and PKCβII pathway, as well as their downstream transcription factors, AP-1 and NF-κB, were involved in 10% stretch induced ACE2 expression. In conclusion, our study indicates ACE2 is a mechanosensitive gene, and may represent a potential therapeutic target for mechanical forces related vascular diseases.

To determine how muscle spindles are involved in the pathophysiology of chronic myofascial trigger spots (MTrSs, similar to myofascial trigger points) in a rat injury model according to the characteristics of the Hoffmann reflex (H-reflex) and the anatomical relationship between muscle spindles and MTrSs.
16 male Sprague-Dawley rats (7 weeks old) were randomly divided into experimental and control groups. A blunt strike injury and eccentric exercise were applied to the gastrocnemius muscle of rats in the experimental group once a week for 8 weeks as a MTrS modelling intervention. Subsequently, the rats were reared normally and rested for 4 weeks. At the end of the 12th week, the rats were examined for the presence of MTrSs defined by the detection of a palpable taut band exhibiting both a local twitch response and spontaneous electrical activity. After modelling, evocation of the H-reflex and morphological examination of muscle spindles and MTrSs were conducted.
The threshold (0.35±0.04 mA) of the H-reflex and latency (1.24±0.18 ms) of the M wave recorded at MTrSs were not significantly different to those at non-MTrSs (P>0.05). Compared with non-MTrSs, a lower Mmax (4.28±1.27 mV), higher Hmax (median (IQR) 0.95 (0.80-1.08) mV) and Hmax/Mmax (median (IQR) 0.21 (0.16-0.40)), and shorter H wave latency (4.60±0.89 ms) were recorded at MTrSs (P<0.05). Morphologically, there was a close anatomical relationship between the MTrS cells and the muscle spindles.
Compared with normal muscles, the H-reflex myoelectrical activity was enhanced and some muscle spindles might have been influenced by active MTrSs. Thus, muscle spindles may play an important role in the pathological mechanism underlying myofascial trigger points.

Vertigo is one of the most common presentations in adult patients. Among the various causes of vertigo, so-called cervical vertigo is still a controversial entity. Cervical vertigo was first thought to be due to abnormal input from cervical sympathetic nerves based on the work of Barré and Liéou in 1928. Later studies found that cerebral blood flow is not influenced by sympathetic stimulation. Ryan and Cope in 1955 proposed that abnormal sensory information from the damaged joint receptors of upper cervical regions may be related to pathologies of vertigo of cervical origin. Further studies found that cervical vertigo seems to originate from diseased cervical intervertebral discs. Recent research found that the ingrowth of a large number of Ruffini corpuscles into diseased cervical discs may be related to vertigo of cervical origin. Abnormal neck proprioceptive input integrated from the signals of Ruffini corpuscles in diseased cervical discs and muscle spindles in tense neck muscles secondary to neck pain is transmitted to the central nervous system and leads to a sensory mismatch with vestibular and other sensory information, resulting in a subjective feeling of vertigo and unsteadiness. Further studies are needed to illustrate the complex pathophysiologic mechanisms of cervical vertigo and to better understand and manage this perplexing entity.

The aim of this study is to explore the effects of abnormal occlusion and functional recovery caused by functional mandible deviation on the head and neck muscles and muscle spindle sensory-motor system by electrophysiological response and endogenous monoamine neurotransmitters\' distribution in the nucleus of the spinal tract. Seven-week-old male Wistar rats were randomly divided into 7 groups: normal control group, 2W experimental control group, 2W functional mandible deviation group, 2W functional mandible deviation recovery group, 4W experimental control group, 4W functional mandible deviation group, 4W functional mandible deviation recovery group. Chewing muscles, digastric muscle, splenius, and trapezius muscle spindles electrophysiological response activities at the opening and closing state were recorded. And then the chewing muscles, digastric, splenius, trapezius, and neck trigeminal nucleus were taken for histidine decarboxylase (HDC) detection by high performance liquid chromatography (HPLC), immunofluorescence, and reverse-transcription polymerase chain reaction (RT-PCR). Histamine receptor proteins in the neck nucleus of the spinal tract were also examined by immunofluorescence and RT-PCR. Electromyography activity of chewing muscles, digastric, and splenius muscle was significantly asymmetric; the abnormal muscle electromyography activity was mainly detected at the ipsilateral side. After functional mandibular deviation, muscle sensitivity on the ipsilateral sides of the chewing muscle and splenius decreased, muscle excitement weakened, modulation depth decreased, and the muscle spindle afferent impulses of excitation transmission speed slowed down. Changes for digastric muscle electrical activity were contrary. The functions recovered at different extents after removing the deflector. However, trapezius in all the experimental groups and recovery groups exhibited bilateral symmetry electrophysiological responses, and no significant difference compared with the control group. After functional mandibular deviation, HDC protein and messenger ribonucleic acid (mRNA) levels on the ipsilateral sides of the chewing muscle and splenius increased significantly. HDC level changes for digastric muscle were contrary. After the removal of the mandibular position deflector, HDC protein and mRNA levels decreased on the ipsilateral sides of the chewing muscle and splenius while they increased in the digastric muscle. The difference of histamine decarboxylase content in the bilateral trapezius in each experimental group was small. After functional mandibular deviation, the temporomandibular joint mechanical receptors not only caused the fusimotor fiber hypoallergenic fatigue slow response on the ipsilateral sides of splenius, but also increased the injury neurotransmitter histamine release. The authors\' results further support the opinion that the temporomandibular joint receptors may be involved in the mechanical theory of the head and neck muscles nervous system regulation.

One goal of neuromorphic engineering is to create \'realistic\' robotic systems that interact with the physical world by adopting neuromechanical principles from biology. Critical to this is the methodology to implement the spinal circuitry responsible for the behavior of afferented muscles. At its core, muscle afferentation is the closed-loop behavior arising from the interactions among populations of muscle spindle afferents, alpha and gamma motoneurons, and muscle fibers to enable useful behaviors.
We used programmable very- large-scale-circuit (VLSI) hardware to implement simple models of spiking neurons, skeletal muscles, muscle spindle proprioceptors, alpha-motoneuron recruitment, gamma motoneuron control of spindle sensitivity, and the monosynaptic circuitry connecting them. This multi-scale system of populations of spiking neurons emulated the physiological properties of a pair of antagonistic afferented mammalian muscles (each simulated by 1024 alpha- and gamma-motoneurones) acting on a joint via long tendons.
This integrated system was able to maintain a joint angle, and reproduced stretch reflex responses even when driving the nonlinear biomechanics of an actual cadaveric finger. Moreover, this system allowed us to explore numerous values and combinations of gamma-static and gamma-dynamic gains when driving a robotic finger, some of which replicated some human pathological conditions. Lastly, we explored the behavioral consequences of adopting three alternative models of isometric muscle force production. We found that the dynamic responses to rate-coded spike trains produce force ramps that can be very sensitive to tendon elasticity, especially at high force output.
Our methodology produced, to our knowledge, the first example of an autonomous, multi-scale, neuromorphic, neuromechanical system capable of creating realistic reflex behavior in cadaveric fingers. This research platform allows us to explore the mechanisms behind healthy and pathological sensorimotor function in the physical world by building them from first principles, and it is a precursor to neuromorphic robotic systems.

Charcot-Marie-Tooth (CMT) is the most common inherited peripheral neuropathy, affecting approximately 2.8 million people. The CMT leads to distal neuropathy that is characterized by reduced motor nerve conduction velocity, ataxia, muscle atrophy and sensory loss. We generated a mouse model of CMT type 2E (CMT2E) expressing human neurofilament light E396K (hNF-LE396K ), which develops decreased motor nerve conduction velocity, ataxia and muscle atrophy by 4 months of age. Symptomatic hNF-LE396K mice developed phenotypes that were consistent with proprioceptive sensory defects as well as reduced sensitivity to mechanical stimulation, while thermal sensitivity and auditory brainstem responses were unaltered. Progression from presymptomatic to symptomatic included a 50% loss of large diameter sensory axons within the fifth lumbar dorsal root of hNF-LE396K mice. Owing to proprioceptive deficits and loss of large diameter sensory axons, we analyzed muscle spindle morphology in presymptomatic and symptomatic hNF-LE396K and hNF-L control mice. Muscle spindle cross-sectional area and volume were reduced in all hNF-LE396K mice analyzed, suggesting that alterations in muscle spindle morphology occurred prior to the onset of typical CMT pathology. These data suggested that CMT2E pathology initiated in the muscle spindles altering the proprioceptive sensory system. Early sensory pathology in CMT2E could provide a unifying hypothesis for the convergence of pathology observed in CMT.