• Archives of Craniofacial Surgery
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• v.22 no.1
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• pp.1-10
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• 2021

Botulinum toxin type A (BoNT-A), onabotulinumtoxinA (Botox) was approved by the United States Food and Drug Administration for temporary improvement of glabellar lines in patients 65 years and younger in 2002, and has also been used widely for aesthetic purposes such as hyperhidrosis, body shape contouring, and other noninvasive facial procedures. BoNT-A inhibits presynaptic exocytosis of acetylcholine (ACh)-containing vesicles into the neuromuscular junction at cholinergic nerve endings of the peripheral nervous system, thereby paralyzing skeletal muscles. ACh is the most broadly used neurotransmitter in the somatic nervous system, preganglionic and postganglionic fibers of parasympathetic nerves, and preganglionic fibers or postganglionic sudomotor nerves of sympathetic nerves. The scientific basis for using BoNT-A in various cosmetic procedures is that its function goes beyond the dual role of muscle paralysis and neuromodulation by inhibiting the secretion of ACh. Although the major target organs for aesthetic procedures are facial expression muscles, skeletal body muscles, salivary glands, and sweat glands, which are innervated by the somatic or autonomic nerves of the peripheral cholinergic nerve system, few studies have attempted to directly explain the anatomy of the areas targeted for injection by addressing the neural physiology and rationale for specific aesthetic applications of BoNT-A therapy. In this article, we classify the various cosmetic uses of BoNT-A according to the relevant component of the peripheral nervous system, and describe scientific theories regarding the anatomy and physiology of the cholinergic nervous system. We also review critical physiological factors and conditions influencing the efficacy of BoNT-A for the rational aesthetic use of BoNT-A. We hope that this comprehensive review helps promote management policies to support long-term, safe, successful practice. Furthermore, based on this, we look forward to developing and expanding new advanced indications for the aesthetic use of BoNT-A in the future.

• IMMUNE NETWORK
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• v.22 no.2
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• pp.20.1-20.9
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• 2022

Despite the high prevalence of chronic dermatitis and the accompanied intractable itch, therapeutics that specifically target itching have low efficacy. Increasing evidence suggests that TLRs contribute to immune activation and neural sensitization; however, their roles in chronic itch remain elusive. Here, we show that the RBL-2H3 mast cell line expresses TLR4 and that treatment with a TLR4 antagonist opposes the LPS dependent increase in mRNA levels of Th2 and innate cytokines. The pathological role of TLR4 activation in itching was studied in neonate rats that developed chronic itch due to neuronal damage after receiving subcutaneous capsaicin injections. Treatment with a TLR4 antagonist protected these rats with chronic itch against scratching behavior and chronic dermatitis. TLR4 antagonist treatment also restored the density of cutaneous nerve fibers and inhibited the histopathological changes that are associated with mast cell activation after capsaicin injection. Additionally, the expression of IL-1β, IL-4, IL-5, IL-10, and IL-13 mRNA in the lesional skin decreased after TLR4 antagonist treatment. Based on these data, we propose that inhibiting TLR4 alleviated itch in a rat model of chronic relapsing itch, and the reduction in the itch was associated with TLR4 signaling in mast cells and nerve fibers.

• Annals of Clinical Neurophysiology
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• v.19 no.2
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• pp.125-130
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• 2017

Background: Routine nerve conduction study (NCS) can only be used to evaluate the function of large fibers, and the results of NCS are often normal in patients with distal sensory polyneuropathy. The measurement of the current perception threshold (CPT) has been reported to represent a variety of peripheral nerve fiber functions. This study was performed to investigate the value of measuring CPT in patients with diabetic sensory polyneuropathy who have no abnormalities in routine NCS. Methods: Twenty-seven diabetic patients with sensory polyneuropathy and normal routine NCS and 18 age-matched control subjects participated in this study. The CPT was measured on the unilateral index finger and great toe of each subject at frequencies of 5 Hz, 250 Hz, and 2,000 Hz. Results: CPT values were significantly higher in the patient group than in the control group, especially with stimuli at the lowest frequency of 5 Hz (p < 0.05). There were significant correlations between the CPT values obtained at three different frequencies in the patient group, whereas the correlation was only significant in the pair of 250 Hz/5 Hz (both in the hands and feet), and in the pair of 2,000 Hz/250 Hz (in the feet) for the control group. Conclusions: Our data suggest that the CPT test, especially at a stimuli frequency of 5 Hz, may be a useful screening tool for diabetic polyneuropathy in patients who show no abnormalities in routine NCS.

• Journal of Korean Neurosurgical Society
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• v.55 no.6
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• pp.370-374
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• 2014

To present a case of cauda equina syndrome (CES) caused by chronic inflammatory demyelinating polyneuropathy (CIDP) which seemed clinically similar to Charcot-Marie-Tooth disease type1 (CMT1). CIDP is an immune-mediated polyneuropathy, either progressive or relapsing-remitting. It is a non-hereditary disorder characterized by symmetrical motor and sensory deficits. Rarely, spinal nerve roots can be involved, leading to CES by hypertrophic cauda equina. A 34-year-old man presented with low back pain, radicular pain, bilateral lower-extremity weakness, urinary incontinence, and constipation. He had had musculoskeletal deformities, such as hammertoes and pes cavus, since age 10. Lumbar spine magnetic resonance imaging showed diffuse thickening of the cauda equina. Electrophysiological testing showed increased distal latency, conduction blocks, temporal dispersion, and severe nerve conduction velocity slowing (3 m/s). We were not able to find genetic mutations at the PMP 22, MPZ, PRX, and EGR2 genes. The pathologic findings of the sural nerve biopsy revealed thinly myelinated nerve fibers with Schwann cells proliferation. We performed a decompressive laminectomy, intravenous IgG (IV-IgG) and oral steroid. At 1 week after surgery, most of his symptoms showed marked improvements except foot deformities. There was no relapse or aggravation of disease for 3 years. We diagnosed the case as an early-onset CIDP with cauda equine syndrome, whose initial clinical findings were similar to those of CMT1, and successfully managed with decompressive laminectomy, IV-IgG and oral steroid.

• Journal of the korean academy of Pediatric Dentistry
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• v.26 no.2
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• pp.350-364
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• 1999

The distribution of mast cells and nerves were investigated in the submandibular and sublingual glands of postnatal rats, using morphometric, histochemical and immunohistochemical techniques. Mast cells were observed in the submandibular and sublingual glands of postnatal development. Number of mast cells gradually increased in both glands following development. At birth, mast cells were relatively fewer in submandibular gland than those in sublingual gland, and they were mainly distributed in parenchymal tissues. At $2{\sim}4$ weeks, most of the mast cells were observed in the connective tissues, surrounding neurovascular elements, but some mast cells were closely related with the acini of submandibular gland. PGP 9.5 immunoreactive nerve fibers were found in the submandibular and sublingual glands of all developmental age. The nerve fibers were showed in varicose shape, and mainly located in adjacent area of ducts and vascular components of both glands. The number of nerve fibers were increased rapidly until 8 weeks, but they were not increased any more until 24 weeks. Therefore, it is suggested that mast cells and nerve fibers related with each other, and that their interactions may play roles not only in maturation of secretory units but also growth and differentiation of the tubular structures of the rat submandibular and sublingual glands during postnatal development.

• International Journal of Oral Biology
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• v.43 no.3
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• pp.155-160
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• 2018

There exists very little information on the ultrastructure of substance P immunopositive (+) fibers in the human dental pulp, which may help in understanding the mechanism for substance P associated pulpal inflammatory pain. To address this issue, we investigated the presence of substance P+ fibers in the human dental pulp by light- and electron-microscopic immunohistochemistry. Light microscopy revealed that substance P+ fibers ran within neurovascular bundles in the radicular pulp and in the core of coronal pulp. They were also frequently present in the peripheral pulp. Substance P+ fibers showed beads like swellings interconnected by thin axonal strand, in a manner similar to bouton en passants and interconnecting axonal strand in the spinal cord. Electron microscopy revealed that almost all the substance P+ axons were unmyelinated. The axonal swellings of the substance P+ contained numerous clear round vesicles (40-50 nm in diameter) and many large dense-cored vesicles (80-110 nm in diameter) as well as many mitochondria. The vesicles and mitochondria were rarely observed in the thin axonal strand interconnecting the swellings. Intimate interrelationship or synaptic structure between the swellings of substance P+ axon and nearby pulpal cells or axons was not found. These findings suggest co-release of substance P and glutamate from the substance P+ pulpal axons and its action on nearby structures in a paracrine manner.

• Archives of Reconstructive Microsurgery
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• v.6 no.1
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• pp.73-79
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• 1997

Complete denervation after severe brachial plexus injury make significant muscle atrophy with loss of proper function. It is much helpful to reconstruct the essential function of the elbow flexion movement in patient with total loss of elbow flexion motion after brachial plexus lesion which was not recovered with nerve surgery or long term conservative treatment from onset. In whole arm type brachial plexus injury, if there were no response to neurotization or neglected from injury, the volume of the denervated muscle is significantely reduced month by month. About 18 months most of the muscle fibers change to fibrous tissues and markedly atrophied irreversibly, further waiting is no more meaningful from that period. Authors performed 14 cases of functioning gracilis muscle transfer from 1981 to 1995 with microneurovascular technique, neuromusculocutaneous free flaps were performed for reconstruction of lost elbow flexion function. Average follow-up period was 5 years and 6 months. We used couple of intercostal nerves as a recipient nerve which were anastomosed to muscular nerve from obturator nerve in all cases. Recipient vessels were three deep brachial artery and eleven brachial artery which were anastomosed to medial femoral circumflex artery with end to end or end to side fashion. Average resting length of the transplanted gracilis were 24 cm. We can get average 54 degree flexion range of elbow with fair muscle power from flail elbow. There were one case of muscle necrosis with lately developed thrombosis of microvascular anastomosed site which comes from insufficient recipient arterial condition, 3 cases of partial marginal necrosis of distal skin of the transplanted part which were not significant problem with spontaneously solved with time goes by gracilis muscle has constant neurovascular pattern with relatively easy harvesting donor with minimal donor morbidity. Especially it has similar length and shape with biceps brachii muscle of upper arm and longer nerve pedicle which can neurorrhaphy with intercostal nerve without nerve graft if sufficient mobilization of the nerves from both sides of gracilis and intercostal region. Authors can propose gracilis muscle transplantation with intercostal nerves neurotization is helpful method with minimal donor morbidity for neglected brachial plexus palsy patients.

• Journal of Oral Medicine and Pain
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• v.36 no.2
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• pp.131-137
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• 2011

Current Perception Threshold (CPT) using Neurometer($Neurometer^{(R)}$ CPT/C) is thought as one of easy and noninvasive QST(qunatitative sensory testing) tools for A${\beta}$, A${\delta}$ and C fibers within a relatively short time. However, conflicts about its reliability still exist. This study aimed to evaluate the reliability of CPTs evaluation and find a way to increase its reliability. Two examiners separately tested CPTs at each side of the mandibluar nerve areas for ten healthy male adults (average age of 22.4 years) three times with an intervals of a week during three weeks. Mean CPTs were compared between the right and left sides of the mandibular nerve area and between the three examinations on the each side. While CPTs at 2000 Hz(A${\beta}$ fiber) showed statistically significant side differences in all three examinations (p<0.05), significant side difference was found in only one examination at 250 Hz(A${\delta}$ fiber) and no difference at 5 Hz(C fiber). Comparing CPTs on the each side of the mandibular nerve area, all examinations at all sensory nerve fibers showed the least CPTs at the 1st examinations. CPTs at 250 Hz(A${\delta}$ fiber) and 5 Hz(C fiber) were significantly different between the first and the following examinations (p<0.05) and there was no significant difference between 2nd and 3rd examinations. The results of this study indicated that CPTs at 250 Hz(A${\delta}$ fiber) and 5 Hz(C fiber) are reliable but CPTs at 2000 Hz(A${\beta}$ fiber) is not appropriate for evaluation of side differences in the mandibular nerve area. In addition, it is suggested that repeated examination be helpful to increase reliability of the CPT evaluation.

• Annals of Clinical Neurophysiology
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• v.3 no.1
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• pp.43-46
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• 2001

Acute pandysautonomic neuropathy(APN) is an uncommon clinical entitiy involving vasomotor, sudomotor, pupilomotor, secretomotor and other autonomic systems. Both sympathetic or parasympathetic fibers are involved with relative preservation of somatic sensory and motor function. Although APN shares several clinical features with GBS, it is not clear whether APN is a subvariety of GBS. We report two young patients with APN. Patient 1 was a 18-year-old girl with recurrent fainting spells. Patient 2 was a 23-year-old man sufferring from unexplained nausea and vomiting. Both had a history of previous upper respiratory infection. They presented with gastroparesis, anhydrosis and orthostatic hypotension. Mild numbness and tingling sense was present, but motor power was intact. Neurologic examination showed bilateral tonic pupil, decreased pain and vibration sense, and absent tendon reflexes. Nerve conduction study indicated diffuse sensorimotor polyneuropathy. Nerve biopsy in patient 2 revealed axonal degeneration. After conservative management, gastrointestinal symptoms were improved in patient 2, however, patient 1 suffered from the symptoms lasting more than several months. These cases suggest that post-infectious dysautonomic symptoms in young patient may indicate the diagnosis of APN. Although the natural course is generally benign, accurate diagnosis and proper management may be mandatory for the better clinical outcome.

• The Korean Journal of Physiology
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• v.21 no.1
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• pp.67-77
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• 1987

Effect of intravenously injected clonidine on the flexion reflex was studied in 15 decerebrated and spinalized cats. The flexion reflex was elicited by electrical stimulation of the tibial nerve or the common peroneal nerve and it was recorded as single unit activity from filaments of the L6 or L7 ventral roots. In order to obtain the late flexion reflex discharges, $A{\delta}$ and C afferent fibers were stimulated with single or train electrical pulses respectively. The flexion reflex, especially the late component, was markedly inhibited after intravenous administration of clonidine. The clonidine-induced inhibition of the flexion reflex was compared before and after treatment of the animals respectively with yohimbine and naloxone. The inhibitory effect on the flexion reflex of clonidine was not altered by naloxone, a ${\mu}-opioid$ receptor blocker, whereas it was completely blocked by yohimbine, an ${\alpha}_2-adrenergic$ antagonist. These results indicate that clonidine inhibits the flexion reflex through excitation of ${\alpha}_2-adrenoceptors$ even at the spinal cord level.