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In peripheral artery disease patients, the blood supply directed to the lower limbs is reduced. This results in severe limb ischemia and thereby enhances pain sensitivity in lower limbs. The painful perception is induced and exaggerate during walking, and is relieved by rest. This symptom is termed by intermittent claudication. The limb ischemia also amplifies autonomic responses during exercise. In the process of pain and autonomic responses originating exercising muscle, a number of receptors in afferent nerves sense ischemic changes and send signals to the central nervous system leading to autonomic responses. This review integrates recent study results in terms of perspectives including how nerve growth factor affects muscle sensory nerve receptors in peripheral artery disease and thereby alters responses of sympathetic nerve activity and blood pressure to active muscle. For the sensory nerve receptors, we emphasize the role played by transient receptor potential vanilloid type 1, purinergic P2X purinoceptor 3 and acid sensing ion channel subtype 3 in amplified sympathetic nerve activity responses in peripheral artery disease.

A new nerve matrix membrane derived from decellularized porcine nerves has been shown to retain the major extracellular matrix components, and to be effective in preventing adhesion between the nerve anastomosis sites and the surrounding tissues in a rat sciatic nerve transection model, thereby enhancing regeneration of the nerve. The effectiveness of the membrane may be attributed to its various bioactive components. In this prospective, randomized, single-blind, parallel-controlled multicenter clinical trial, we compared the safety and efficacy of the new nerve matrix membrane with a previously approved bovine tendon-derived type I collagen nerve wrapping. A total of 120 patients with peripheral nerve injury were recruited from Beijing Jishuitan Hospital, The First Bethune Hospital of Jilin University, and Yantai Yuhuangding Hospital, China. The patients were randomly assigned to undergo end-to-end and tension-free neurorrhaphy with nerve matrix membrane (n = 60, 52 male, 8 female, mean age 41.34 years, experimental group) or tendon-derived collagen nerve wrapping (n = 60, 42 male, 18 female, mean age 40.17 years, control group). Patients were followed-up at 14 ± 5, 30 ± 7, 90 ± 10 and 180 ± 20 days after the operation. Safety evaluation included analyses of local and systemic reactions, related laboratory tests, and adverse reactions. Efficacy evaluation included a static 2-point discrimination test, a moving 2-point discrimination test, and a Semmes-Weinstein monofilament examination. Sensory nerve function was evaluated with the British Medical Research Council Scale and Semmes-Weinstein monofilament examination. The ratio (percentage) of patients with excellent to good results in sensory nerve recovery 180 ± 20 days after the treatment was used as the primary effectiveness index. The percentages of patients with excellent to good results in the experimental and control groups were 98.00% and 94.44%, respectively, with no significant difference between the two groups. There were no significant differences in the results of routine blood tests, liver and renal function tests, coagulation function tests, or immunoglobulin tests at 14 and 180 days postoperatively between the two groups. These findings suggest that the novel nerve matrix membrane is similar in efficacy to the commercially-available bovine-derived collagen membrane in the repair of peripheral nerve injury, and it may therefore serve as an alternative in the clinical setting. The clinical trial was approved by the Institutional Ethics Committee of Beijing Jishuitan Hospital, China (approval No. 20160902) on October 8, 2016, the Institutional Ethics Committee of the First Bethune Hospital of Jilin University, China (approval No. 160518-088) on December 14, 2016, and the Institutional Ethics Committee of Yantai Yuhuangding Hospital, China (approval No. 2016-10-01) on December 9, 2016. The clinical trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2000033324) on May 28, 2020.

Sensory and motor nerve fibers of peripheral nerves have different anatomies and regeneration functions after injury. To gain a clear understanding of the biological processes behind these differences, we used a labeling technique termed isobaric tags for relative and absolute quantitation to investigate the protein profiles of spinal nerve tissues from Sprague-Dawley rats. In response to Wallerian degeneration, a total of 626 proteins were screened in sensory nerves, of which 368 were upregulated and 258 were downregulated. In addition, 637 proteins were screened in motor nerves, of which 372 were upregulated and 265 were downregulated. All identified proteins were analyzed using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of bioinformatics, and the presence of several key proteins closely related to Wallerian degeneration were tested and verified using quantitative real-time polymerase chain reaction analyses. The differentially expressed proteins only identified in the sensory nerves were mainly relevant to various biological processes that included cell-cell adhesion, carbohydrate metabolic processes and cell adhesion, whereas differentially expressed proteins only identified in the motor nerves were mainly relevant to biological processes associated with the glycolytic process, cell redox homeostasis, and protein folding. In the aspect of the cellular component, the differentially expressed proteins in the sensory and motor nerves were commonly related to extracellular exosomes, the myelin sheath, and focal adhesion. According to the Kyoto Encyclopedia of Genes and Genomes, the differentially expressed proteins identified are primarily related to various types of metabolic pathways. In conclusion, the present study screened differentially expressed proteins to reveal more about the differences and similarities between sensory and motor nerves during Wallerian degeneration. The present findings could provide a reference point for a future investigation into the differences between sensory and motor nerves in Wallerian degeneration and the characteristics of peripheral nerve regeneration. The study was approved by the Ethics Committee of the Chinese PLA General Hospital, China (approval No. 2016-x9-07) in September 2016.

For severe cubital tunnel syndrome, patients with absent sensory nerve action potential tend to have more severe nerve damage than those without. Thus, it is speculated that such patients generally have a poor prognosis. How absent sensory nerve action potential affects surgical outcomes remains uncertain owing to a scarcity of reports and conflicting results. This retrospective study recruited one hundred and fourteen cases (88 patients with absent sensory nerve action potential and 26 patients with present sensory nerve action potential) undergoing either subcutaneous transposition or in situ decompression. The minimum follow-up was set at 2 years. Primary outcome measures of overall hand function included their McGowan grade, modified Bishop score, and Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH) score. For patients with absent sensory nerve action potential, 71 cases (80.7%) achieved at least one McGowan grade improvement, 76 hands (86.4%) got good or excellent results according to the Bishop score, and the average DASH score improved 49.5 points preoperatively to 13.1 points postoperatively. When compared with the present sensory nerve action potential group, they showed higher postoperative McGowan grades and DASH scores, but there was no statistical difference between the modified Bishop scores of the two groups. Following in situ decompression or subcutaneous transposition, great improvement in hand function was achieved for severe cubital tunnel syndrome patients with absent sensory nerve action potential. The functional outcomes after surgery for severe cubital tunnel syndrome are worse in patients with absent sensory nerve action potential than those without. This study was approved by the Ethical Committee of Huashan Hospital, Fudan University, China (approval No. 2017142).

End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve. It involves suturing the distal stump of the disconnected nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve). However, the motor-sensory specificity after end-to-side neurorrhaphy remains unclear. This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and cutaneous antebrachii medialis nerve were just exposed; and (3) the transected nerve group: cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied. At 5 months, acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group, and none of the myelinated axons were stained in either the sham or transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%. In contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment. These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy.

Motor nerves and sensory nerves conduct signals in different directions and function in different ways. In the surgical treatment of peripheral nerve injuries, the best prognosis is obtained by keeping the motor and sensory nerves separated and repairing the nerves using the suture method. However, the clinical consequences of connections between sensory and motor nerves currently remain unknown. In this study, we analyzed the anatomical structure of the rat femoral nerve, and observed the motor and sensory branches of the femoral nerve in the quadriceps femoris. After ligation of the nerves, the proximal end of the sensory nerve was connected with the distal end of the motor nerve, followed by observation of the changes in the newly-formed regenerated nerve fibers. Acetylcholinesterase staining was used to distinguish between the myelinated and unmyelinated motor and sensory nerves. Denervated muscle and newly formed nerves were compared in terms of morphology, electrophysiology and histochemistry. At 8 weeks after connection, no motor nerve fibers were observed on either side of the nerve conduit and the number of nerve fibers increased at the proximal end. The proportion of newly-formed motor and sensory fibers was different on both sides of the conduit. The area occupied by autonomic nerves in the proximal regenerative nerve was limited, but no distinct myelin sheath was visible in the distal nerve. These results confirm that sensory and motor nerves cannot be effectively connected. Moreover, the change of target organ at the distal end affects the type of nerves at the proximal end.

Exogenous substance P accelerates wound healing in diabetes, but the mechanism remains poorly understood. Here, we established a rat model by intraperitoneally injecting streptozotocin. Four wounds (1.8 cm diameter) were drilled using a self-made punch onto the back, bilateral to the vertebral column, and then treated using amniotic membrane with epidermal stem cells and/or substance P around and in the middle of the wounds. With the combined treatment the wound-healing rate was 100% at 14 days. With prolonged time, type I collagen content gradually increased, yet type III collagen content gradually diminished. Abundant protein gene product 9.5- and substance P-immunoreactive nerve fibers regenerated. Partial nerve fiber endings extended to the epidermis. The therapeutic effects of combined substance P and epidermal stem cells were better than with amniotic membrane and either factor alone. Our results suggest that the combination of substance P and epidermal stem cells effectively contributes to nerve regeneration and wound healing in diabetic rats.

The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peripheral nerve is still unknown. This study explored the problem in a femoral nerve section model in rats. L1 and semaphorin 3A mRNA and protein expressions were measured over the 4-week recovery period. Quantitative polymerase chain reaction showed that nerve cell adhesion molecule L1 expression was higher in the sensory nerves than in motor nerves at 2 weeks after injury, but vice versa for the expression of semaphorin 3A. Western blot assay results demonstrated that nerve cell adhesion molecule L1 expression was higher in motor nerves than in the sensory nerves at the proximal end after injury, but its expression was greater in the sensory nerves at 2 weeks. Semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 3 days and 1 week after injury. Nerve cell adhesion molecule L1 and semaphorin 3A expressions at the distal end were higher in the motor nerves than in the sensory nerves at 3 days, 1 and 2 weeks. Immunohistochemical staining results showed that nerve cell adhesion molecule L1 expression at the proximal end was greater in the sensory nerves than in the motor nerves; semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 2 weeks after injury. Taken together, these results indicated that nerve cell adhesion molecules L1 and semaphorin 3A exhibited different expression patterns at the proximal and distal ends of sensory and motor nerves, and play a coordinating role in neural chemotaxis regeneration.

Human periodontal ligament stem cells are easily accessible and can differentiate into Schwann cells. We hypothesized that human periodontal ligament stem cells can be used as an alternative source for the autologous Schwann cells in promoting the regeneration of injured peripheral nerve. To validate this hypothesis, human periodontal ligament stem cells (1 × 10(6)) were injected into the crush-injured left mental nerve in rats. Simultaneously, autologous Schwann cells (1 × 10(6)) and PBS were also injected as controls. Real-time reverse transcriptase polymerase chain reaction showed that at 5 days after injection, mRNA expression of low affinity nerve growth factor receptor was significantaly increased in the left trigeminal ganglion of rats with mental nerve injury. Sensory tests, histomorphometric evaluation and retrograde labeling demonstrated that at 2 and 4 weeks after injection, sensory function was significantly improved, the numbers of retrograde labeled sensory neurons and myelinated axons were significantly increased, and human periodontal ligament stem cells and autologous Schwann cells exhibited similar therapeutic effects. These findings suggest that transplantation of human periodontal ligament stem cells show a potential value in repair of mental nerve injury.

The present study utilized samples from bilateral motor branches of the femoral nerve, as well as saphenous nerves, ventral roots, and dorsal roots of the spinal cord, to detect differential protein expression using two-dimensional gel electrophoresis and nano ultra-high performance liquid chromatography electrospray ionization mass spectrometry tandem mass spectrometry techniques. A mass spectrum was identified using the Mascot search. Results revealed differential expression of 11 proteins, including transgelin, Ig kappa chain precursor, plasma glutathione peroxidase precursor, an unnamed protein product (gi|55628), glyceraldehyde-3-phosphate dehydrogenase-like protein, lactoylglutathione lyase, adenylate kinase isozyme 1, two unnamed proteins products (gi|55628 and gi|1334163), and poly(rC)-binding protein 1 in motor and sensory nerves. Results suggested that these proteins played roles in specific nerve regeneration following peripheral nerve injury and served as specific markers for motor and sensory nerves.

Human acellular nerve allografts have a wide range of donor origin and can effectively avoid nerve injury in the donor area. Very little is known about one-stage reconstruction of digital nerve defects. The present study observed the feasibility and effectiveness of human acellular nerve allograft in the reconstruction of < 5-cm digital nerve defects within 6 hours after injury. A total of 15 cases of nerve injury, combined with nerve defects in 18 digits from the Department of Emergency were enrolled in this study. After debridement, digital nerves were reconstructed using human acellular nerve allografts. The patients were followed up for 6-24 months after reconstruction. Mackinnon-Dellon static two-point discrimination results showed excellent and good rates of 89%. Semmes-Weinstein monofilament test demonstrated that light touch was normal, with an obvious improvement rate of 78%. These findings confirmed that human acellular nerve allograft for one-stage reconstruction of digital nerve defect after hand injury is feasible, which provides a novel trend for peripheral nerve reconstruction.

Paresthesia is the name given to a temporary or permanent sensory loss caused by several surgical procedures that affected the peripheral sensory nerve. In dentistry, common iatrogenic procedures that can lead to sensory loss include third molar removal, blocking of the inferior alveolar nerve (local anesthesia), orthognathic surgery, implant placement, surgical removal of cysts or tumors and facial trauma.

Cutaneous nerve injury is the most common complication following foot and ankle surgery. However, clinical studies including long-term follow-up data after cutaneous nerve injury of the foot and ankle are lacking. In the current retrospective study, we analyzed the clinical data of 279 patients who underwent foot and ankle surgery. Subjects who suffered from apparent paresthesia in the cutaneous sensory nerve area after surgery were included in the study. Patients received oral vitamin B12 and methylcobalamin. We examined final follow-up data of 17 patients, including seven with sural nerve injury, five with superficial peroneal nerve injury, and five with plantar medial cutaneous nerve injury. We assessed nerve sensory function using the Medical Research Council Scale. Follow-up immediately, at 6 weeks, 3, 6 and 9 months, and 1 year after surgery demonstrated that sensory function was gradually restored in most patients within 6 months. However, recovery was slow at 9 months. There was no significant difference in sensory function between 9 months and 1 year after surgery. Painful neuromas occurred in four patients at 9 months to 1 year. The results demonstrated that the recovery of sensory function in patients with various cutaneous nerve injuries after foot and ankle surgery required at least 6 months.

Studies have shown that sensory nerve damage can activate the p38 mitogen-activated protein kinase (MAPK) pathway, but whether the same type of nerve injury after exercise activates the p38MAPK pathway remains unclear. Several studies have demonstrated that nerve growth factor may play a role in the repair process after peripheral nerve injury, but there has been little research focusing on the hypoglossal nerve injury and repair. In this study, we designed and established rat models of hypoglossal nerve crush injury and gave intraperitoneal injections of exogenous nerve growth factor to rats for 14 days. p38MAPK activity in the damaged neurons was increased following hypoglossal nerve crush injury; exogenous nerve growth factor inhibited this increase in acitivity and increased the survival rate of motor neurons within the hypoglossal nucleus. Under transmission electron microscopy, we found that the injection of nerve growth factor contributed to the restoration of the morphology of hypoglossal nerve after crush injury. Our experimental findings indicate that exogenous nerve growth factor can protect damaged neurons and promote hypoglossal nerve regeneration following hypoglossal nerve crush injury.

Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.