Proprioceptive innervation of the human lips.

The objective of this study was to analyze the proprioceptive innervation of human lips, especially of the orbicularis oris muscle, since it is classically accepted that facial muscles lack typical proprioceptors, that is, muscle spindles, but recently this has been doubted. Upper and lower human lips (n = 5) from non-embalmed frozen cadavers were immunostained for detection of S100 protein (to identify nerves and sensory nerve formations), myosin heavy chain (to label muscle fibers within muscle spindles), and the mechano-gated ion channel PIEZO2. No muscle spindles were found, but there was a high density of sensory nerve formations, which were morphologically heterogeneous, and in some cases resemble Ruffini-like and Pacinian sensory corpuscles. The axons of these sensory formations displayed immunoreactivity for PIEZO2. Human lip muscles lack typical proprioceptors but possess a dense sensory innervation which can serve the lip proprioception.

Immunohistochemical detection of PIEZO1 and PIEZO2 in human digital Meissner´s corpuscles.

BACKGROUND: The cutaneous end organ complexes or cutaneous sensory corpuscles are specialized sensory organs associated to low-threshold mechanoreceptors. Mechano-gated proteins forming a part of ion channels have been detected in both the axon and terminal glial cells of Meissner corpuscles, a specific cutaneous end organ complex in the human glabrous skin. The main candidates to mechanotransduction in Meissner corpuscles are members of the Piezo family of cationic ion channels. PIEZO2 has been detected in the axon of these sensory structures whereas no data exists about the occurrence and cell localization of PIEZO1. METHODS: Skin samples (n = 18) from the palmar aspect of the distal phalanx of the first and second fingers were analysed (8 female and 10 males; age range 26 to 61 26-61 years). Double immunofluorescence for PIEZO1 and PIEZO2 together with axonal or terminal glial cell markers was captured by laser confocal microscopy, and the percentage of PIEZOs positive Meissner corpuscles was evaluated. RESULTS: MCs from human fingers showed variable morphology and degree of lobulation. Regarding the basic immunohistochemical profile, in all cases the axons were immunoreactive for neurofilament proteins, neuron specific enolase and synaptophysin, while the lamellar cells displayed strong S100P immunoreactivity. PIEZO1 was detected co-localizing with axonal markers, but never with terminal glial cell markers, in the 56% of Meissner corpuscles; weak but specific immunofluorescence was additionally detected in the epidermis, especially in basal keratinocytes. Similarly, PIEZO2 immunoreactivity was found restricted to the axon in the 85% of Meissner corpuscles. PIEZO2 positive Merkel cells were also regularly found. CONCLUSIONS: PIEZO1 and PIEZO2 are expressed exclusively in the axon of a subpopulation of human digital Meissner corpuscles, thus suggesting that not only PIEZO2, but also PIEZO1 may be involved in the mechanotransduction from low-threshold mechanoreceptors.

Quantifying spatial acuity of frequency resolved midair ultrasound vibrotactile stimuli.

Spatial acuity is a fundamental property of any sensory system. In the case of the somatosensory system, the two-point discrimination (2PD) test has long been used to investigate tactile spatial resolution. However, the somatosensory system comprises three main mechanoreceptive channels: the slowly adapting channel (SA) responds to steady pressure, the rapidly adapting channel (RA) responds to low-frequency vibration, and the Pacinian channel (PC) responds to high-frequency vibration. The use of mechanical stimuli in the classical 2PD test means that previous studies on tactile acuity have primarily focussed on the pressure-sensitive channel alone, while neglecting other submodalities. Here, we used a novel ultrasound stimulation to systematically investigate the spatial resolution of the two main vibrotactile channels. Contrary to the textbook view of poor spatial resolution for PC-like stimuli, across four experiments we found that high-frequency vibration produced surprisingly good spatial acuity. This effect remained after controlling for interchannel differences in stimulus detectability and perceived intensity. Laser doppler vibrometry experiments confirmed that the acuity of the PC channel was not simply an artifact of the skin's resonance to high-frequency mechanical stimulation. Thus, PC receptors may transmit substantial spatial information, despite their sparse distribution, deep location, and large receptive fields.

Topographical Analysis of Pacinian Corpuscle in the Pulp of Human Cadaver Finger Tip Pulp: A Pilot Cadaver Study.

Background: The human hand is a specialised organ for fine motion and sensation and has a relatively large representation in the homunculus. The pathway of sensation starts from information sent by mechanoreceptors in the hand. This study reports the topography of the Pacinian corpuscle in the fingertips of a human cadaver. Methods: All 10 digits from both hands of a fresh-frozen cadaver were examined. Glabrous skin distal to the distal interphalangeal joint was harvested superficial to the periosteum including fat and subcutaneous tissue. The glabrous skin were divided into 10 sections that included five distal and five proximal sections. Modified gold chloride staining was performed. Sectioned specimens were observed under a light microscope and the density of Pacinian corpuscles was determined in each segment. The density of the corpuscles was compared between the radial/ulnar and proximal/distal segments and also between digits from the right hand versus those from the left hand. Results: Pacinian corpuscles were observed only in the subcutaneous tissue. There was no significant difference in density of the corpuscles between the distal and proximal segments or between the right and left hands. There was a statistically significant greater density of Pacinian corpuscles on the radial segments of all digits except the thumb. Conclusions: There is a greater density of Pacinian corpuscles on the radial side of the human fingertip in all digits except the thumb.

Pacinian corpuscle hyperplasia in a 6-year-old girl.

We present a rare case of Pacinian corpuscle hyperplasia (PCH) presenting with typical finger pain in a 6-year-old girl. As appendages in children are smaller than those in adults, diagnostic criteria are needed for pathological confirmation of PCH in pediatric patients.

Digital Neuropathy by Hypertrophy and Hyperplasia of Pacinian Corpuscle - Usefulness of Microscopic Resection.

We present a patient with Pacinian corpuscle hypertrophy and hyperplasia in the hand and discuss the diagnosis and treatment of this rare condition. A 46-year-old woman presented with radiating pain of the left middle finger. A strong Tinel-like sign was elicited between the index and middle fingers. The patient frequently used mobile phone, with the corner of the phone consistently applying pressure on the palm. The surgery was carried out under the microscope and two enlarged cystic lesions under the epineurium were found in the proper digital nerve. Histologic examination revealed hypertrophied Pacinian corpuscle with normal structure. Postoperatively, her symptoms gradually improved. Preoperative diagnosis of this disease is very difficult. Hand surgeons should keep this disease in mind preoperatively. In our case, we would not have been able to identify multiple hypertrophic Pacinian corpuscles without the microscope. An operating microscope is recommended in a surgery of this nature. Level of Evidence: Level V (Therapeutic).

The acquisition of mechanoreceptive competence by human digital Merkel cells and sensory corpuscles during development: An immunohistochemical study of PIEZO2.

BACKGROUND: PIEZO2 is a transmembrane protein forming part of an ion channel required for mechanotransduction. In humans, PIEZO2 is present in axon terminals of adult Meissner and Pacinian corpuscles, as well as Merkel cells in Merkel cell-neurite complexes. METHODS: To study the acquisition of functional capability for mechanotransduction of developing type I slowly adapting low-threshold mechanoreceptors, i.e., Merkel cell-neurite complexes, a battery of immunohistochemical and immunofluorescence techniques was performed on human skin specimens covering the whole development and growth, from 11 weeks of estimated gestational age to 20 years of life. In addition, developmental expression of PIEZO2 type I (Meissner's corpuscles) and type II (Pacinian corpuscles) rapidly adapting mechanoreceptors was studied in parallel. RESULTS: The first evidence of Merkel cells showing the typical morphology and placement was at 13 weeks of estimated gestation age, and at this time positive immunoreactivity for PIEZO2 was achieved. PIEZO2 expression in axons terminals started at 23 WEGA in Pacinian corpuscles and at 36 WEGA in the case of Meissner corpuscles. The occurrence of PIEZO2 in Merkel cells, Meissner and Pacinian corpuscles was maintained for all the time investigated. Interestingly PIEZO2 was absent in most Aß type I slowly adapting low-threshold mechanoreceptors that innervate MC while it was regularly present in most Aß type I and type II rapidly adapting low-threshold mechanoreceptors that supplies Meissner and Pacinian corpuscles. CONCLUSION: The present results provide evidence that human cutaneous mechanoreceptors could perform mechanotransduction already during embryonic development.

Synaptophysin is a selective marker for axons in human cutaneous end organ complexes.

BACKGROUND: Small clear synaptic-like vesicles fill axon terminals of mechanoreceptors. Their functional significance is controversial and probably includes release of neurotransmitters from afferent axon terminals. Synaptophysin, a major protein of the synaptic vesicle membrane, is present in presynaptic endings of the central and peripheral nervous systems. It is also expressed in mechanosensory neurons which extend into skin forming sensory corpuscles. Nevertheless, synaptophysin occurrence in these structures has never been investigated. METHODS: Here we used immunohistochemistry to detect synaptophysin in adult human dorsal root ganglia, cutaneous Meissner and Pacinian corpuscles and Merkel cell-neurite complexes from foetal to elderly period. Moreover, we analyzed whether synaptophysin co-localizes with the mechano-gated protein PIEZO2. RESULTS: Synaptophysin immunoreactivity was observed in primary sensory neurons (36 ± 6%) covering the entire soma size ranges. Axons of Meissner's and Pacinian corpuscles were positive for synaptophysin from 36 and 12 weeks of estimated gestational age respectively, to 72 years old. Synaptophysin was also detected in Merkel cells (from 14 weeks of estimated gestational age to old age). Additionally in adult skin, synaptophysin and PIEZO2 co-localized in the axon of Meissner and Pacinian corpuscles, Merkel cells as well as in some axons of Merkel cell-neurite complexes. CONCLUSION: Present results demonstrate that a subpopulation of primary sensory neurons and their axon terminals forming cutaneous sensory corpuscles contain synaptophysin, a typical presynaptic vesicle protein. Although the functional relevance of these findings is unknown it might be related to neurotransmission mechanisms linked to mechanotransduction.

First case report of Pacinian corpuscle hyperplasia following complex regional pain syndrome.

Pacinian disorders are exceedingly rare, and the exact pathogenesis is still unknown. The most common symptoms are pain, sensory changes, and a visible or palpable mass, and diagnosis is usually made by pathological examination after the excision of the painful nodule. In this case report, we present the case of a 49-year-old male with Pacinian corpuscle hyperplasia located on the metacarpophalangeal joint, emerging at the same hand of the patient two years after the treatment due to complex regional pain syndrome (CRPS). To the best of our knowledge, this is the first case report revealing the association of CRPS with hyperplasia of Pacinian corpuscles.

Sensory innervation of the human palmar aponeurosis in healthy individuals and patients with palmar fibromatosis.

The human palmar aponeurosis is involved in hand proprioception, and it contains different sensory corpuscle morphotypes that serve this role. In palmar fibromatosis (classically referred to as Dupuytren's disease), the palmar aponeurosis undergoes fibrous structural changes that, presumably, also affect the nervous system, causing altered perception. We analysed the various sensory nerve formation morphotypes in the palmar aponeuroses of healthy subjects and patients with palmar fibromatosis. To do this, we used immunohistochemistry for corpuscular constituents and the putative mechanoproteins PIEZO2 and acid-sensing ion channel 2. Free nerve endings and Golgi-Mazzoni, Ruffini, paciniform and Pacinian corpuscles were identified in both the healthy and the pathological conditions. The densities of the free nerve endings and Golgi-Mazzoni corpuscles were slightly increased in the pathological tissues. Furthermore, the Pacinian corpuscles were enlarged and displayed an altered shape. Finally, there was also morphological and immunohistochemical evidence of occasional denervation of the Pacinian corpuscles, although no increase in their number was observed. Both PIEZO2 and acid-sensing ion channel 2 were absent from the altered corpuscles. These results indicate that the human palmar aponeurosis is richly innervated, and the free nerve endings and sensory corpuscles within the palmar aponeurosis undergo quantitative and qualitative changes in patients with palmar fibromatosis, which may explain the sensory alterations occasionally reported for this pathology.

Intriguing Localisation of "Pacinian Neuroma'' Diagnosed at Intraoperative Consultation during Whipple Procedure.

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Macrodystrophia Lipomatosa of the Foot: A Case Report of MRI and Histologic Findings Including Pacinian Corpuscle Abnormalities.

CASE: A 37-year-old man presented with pain and macrodactyly of a toe. Imaging and histology demonstrated findings consistent with macrodystrophia lipomatosa (MDL). We compared our findings with control tissue obtained from an identical site of a fresh-frozen cadaveric foot from the same anatomical site. Pacinian corpuscles (PCs) in the MDL tissue were increased in number, size, and shape compared with the control tissue and demonstrated edematous interstitial lamellae and vacuolar degenerative change. We also document the magnetic resonance imaging findings of the PCs. CONCLUSION: Peculiar abnormalities of PCs in MDL underline nerve damage and may be a contributing factor in the pain associated with this unusual condition.

Relationship between lamellar sensory corpuscles distributed along the upper arm's deep arteries and pulsating sensation of blood vessels.

Vibration is detected by mechanoreceptors, including Pacinian corpuscles (PCs), which are widely distributed in the human body including the adventitia of large blood vessels. Although the distribution of PCs around large limb vessels has been previously reported, there remains no consensus on their distribution in the adventitia of the human deep blood vessels in the upper arm. In addition, the physiological functions of PCs located around the deep limb blood vessels remain largely unknown. This study aimed to elucidate detailed anatomical features and physiological function of lamellar sensory corpuscles structurally identified as PCs using the immunohistochemical methods around the deep vessels in the upper arm. We identified PCs in the connective tissue adjacent to the deep vessels in the upper arm using histological analysis and confirmed that PCs are located in the vascular sheath of the artery and its accompanying vein as well as in the connective tissue surrounding the vascular sheath and nerves. PCs were densely distributed on the distal side of deep vessels near the elbow. We also examined the relationship between vascular sound and pulsating sensation to evaluate the PCs functions around deep arteries and veins and found that the vascular sound made by pressing the brachial arteries in the upper arm was associated with the pulsating sensation of the examinee. Our results suggest that PCs, around deep vessels, function as bathyesthesia sensors by detecting vibration from blood vessels.

Distribution of sole Pacinian corpuscles: a histological study using near-term human feet.

INTRODUCTION: Fast-adapting afferent input from the sole Pacinian corpuscles (PCs) is essential for walking. However, the distribution of PCs in the plantar subcutaneous tissue remains unknown. MATERIALS AND METHODS: Using histological sections tangential to the plantar skin of eight near-term fetuses, we counted 528-900 PCs per sole. RESULTS: Almost half of the sole PCs existed at the level of the proximal phalanx, especially on the superficial side of the long flexor tendons and flexor digitorum brevis. Conversely, the distribution was less evident on the posterior side of the foot. The medial margin of the sole contained fewer PCs than the lateral margin, possibly due to the transverse arch. In contrast to a cluster formation in the anterior foot, posterior PCs were almost always solitary, with a distance greater than 0.5 mm to the nearest PC. DISCUSSION AND CONCLUSION: Because a receptive field of PCs is larger than that of the other receptors, fewer solitary PCs might cover the posterior sole. In infants, the amount of anterior sole PCs seemed to determine the initial walking pattern using the anterior foot without heel contact. Anterior PCs concentrated along flexor tendons might play a transient role as tendon organs during the initial learning of walking. During a lesson in infants, mechanical stress from the tendon and muscle was likely to degrade the PCs. In the near term, the sole PCs seemed not to be a mini-version of the adult morphology but suggested an infant-specific function.

Bilateral symptomatic Pacinian corpuscle hyperplasia of the adult foot.

Pacinian hyperplasia in the human body has been rarely described in the literature with most cases reported involving the hand (Fassola et al., 2019). This hyperplasia is considered a reactive lesion as opposed to a neoplasm (Satge et al., 2001), with the most common presenting complaint being pain and swelling (Fassola et al., 2019). In this study, a case of bilateral Pacinian corpuscle hyperplasia in the adult foot not previously described in the literature is presented.

Novel observations of Pacinian corpuscle distribution in the hands and feet based on high-resolution 7-T MRI in healthy volunteers.

Pacinian corpuscles represent special nerve endings that serve as mechanoreceptors sensitive to vibration and pressure and are crucial for proprioception. This work demonstrates that the complex network of Pacinian corpuscles in hands and feet can be examined with three-dimensional Dual Echo Steady State (DESS) MR imaging at 7 T, while previous dedicated MRI reports were either limited to two-dimensional images or focused on the hands. The high-resolution MR images show the detailed architecture of the complex receptor network and reveal a "chain-like" arrangement of Pacinian corpuscles, a predilection for clustering around metacarpophalangeal/metatarsophalangeal joints, proximal phalanges and fingertips, and specific sensor locations both in the superficial subcutaneous tissue and adjacent to deep soft tissue structures such as tendons and joint capsules.