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. 2021 Feb 1;239(1):101–110. doi: 10.1111/joa.13398

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

Yoshiyuki Onishi 1, Haruka Hisato 1, Seishi Maeda 1, Yusuke Minato 1, Sachi Kuwahara‐Otani 1, Hideshi Yagi 1,✉
PMCID: PMC8197943  PMID: 33527396

Abstract

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.

Keywords: bathyesthesia, mechanoreceptor, Pacinian corpuscles, vascular sheath, vibration

This study aimed to elucidate detailed anatomical features and physiological function of lamellar sensory corpuscles structurally identified as Pacinian corpuscles using the immunohistochemical methods around the deep vessels in the upper arm. We confirmed that lamellar sensory corpuscles are densely distributed on the distal side of deep vessels near the elbow. Our results suggest that PCs, around deep vessels, function as bathyesthesia sensors by detecting vibration from blood vessels.

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1. INTRODUCTION

Vibration is detected by mechanoreceptors, including Pacinian corpuscles (PCs), Meissner's corpuscles, Merkel's disk, paciniform endings, and lanceolate endings of the hair follicle (Heidenreich et al., 2012; Johnson, 2001; Lechner & Lewin, 2013; Verrillo, 2009). These receptors detect mechanical disturbances imposed on the surface of the skin (Verrillo, 2009). Sensitivity to the frequency of vibration differs among mechanoreceptors, while the maximum sensitivity of PCs lays approximately 200 Hz (Bolanowsky & Verrillo, 1982; Pawson et al., 2008; Sato, 1961). PCs consist of a terminal neurite and concentric lamellae surrounding the terminal neurite. The myelinated nerve enters PCs and forms a terminal neurite without myelin. The inner part of the concentric lamellae, inner core, is made up of non‐neuronal cytoplasmic layers of inner core cells derived from Schwann cells (Bell et al., 1994; Zelená, 1978), while the outer core and external capsule are made up from flattened multiple lamellae. Each lamella consists of single‐layered sheet like cells (Bell et al., 1994; Shanthaveerappa & Bourne, 1963). Between the outer and the inner cores, there is an intermediate growth zone that is not obvious in the mature PC (Pease & Quilliam, 1957).

PCs are densely distributed in the palms of the hands and the soles of the feet in humans. In the hand, PCs play a role in texture perception of materials by detecting vibrations made by the fingerprints showing a frequency of approximately 200 Hz (Scheibert et al., 2009). PCs are also distributed in various human body structures, such as pancreas, articular capsules, fasciae, lymph nodes, and the adventitia of large blood vessels (Benjamin, 2009; Feito et al., 2017; García‐Suárez et al., 2010; Halata et al., 1985; Hogervorst & Brand, 1998; Stark et al., 1998; Stecco et al., 2006; Woollard & Weddell, 1935; Zimny & Wink, 1991). Several previous studies have investigated the distribution of PCs around deep arteries in the extremities. We recently elucidated the detailed distribution of PCs around the femoral artery (Morishita et al., 2018). However, as for the upper limbs, there remains a lack of consensus on the distribution of PCs around the deep vessels. While one study showed that several PCs are located in the adventitia of brachial, radial, and ulnar arteries (Woolland & Weddell, 1935), another reported no PCs in the adventitia of brachial vessels (Roberts, 1959).

Although these deeply situated PCs detected vibrations generated by a 125 Hz tuning fork at bony prominences including the acromion, styloid process of the radius, and lateral malleolus (Fuller, 2010), the physiological functions of deeply situated PCs including PCs around deep vessels of humans remain unclear. The purpose of the present study was to elucidate detailed distribution‐ and morphology‐related features and the unknown physiological functions of PCs localized near deep arteries and veins in the human upper arm. Herein, we report the distribution of PCs around deep blood vessels in the human upper arm and show the possible role of deeply situated PCs in the human upper arm.

2. MATERIALS AND METHODS

2.1. Analysis of the distribution and morphology of lamellar sensory corpuscles

2.1.1. Cadavers

We performed investigations using two cadavers of Japanese men aged 80 and 84 years at the time of death; these cadavers were donated for education at the Hyogo College of Medicine in 2018–2019 and had given written informed consent for scientific investigations prior to death. The present study was approved by the Ethics Review Board of the Hyogo College of Medicine (No. 2976).

2.1.2. Histological analysis

Brachial tissues including brachial, radial, and ulnar arteries and veins were resected from the cadavers and cut into 6.3–14.2 mm thick sections. The tissues were decalcified using K‐CX (FALMA) before being dehydrated in graded ethanol series and soaked in xylene. Samples were subsequently soaked in melting paraffin and embedded in paraffin. The materials derived from right side of a single cadaver were cut into 7 μm thick successive transverse sections using a microtome. Sections at 140‐μm intervals (every 20th section) were mounted onto standard glass slides and subjected to histological staining using Lillie‐Mayer's hematoxylin and eosin. The materials in the middle and distal portions of the upper arm derived from the left side of the cadaver and both sides of the other cadaver were sectioned and stained as described above. Stained sections were observed under an optical microscope equipped with a CCD camera (Olympus BX51 and DP73, Olympus Corp.). We analyzed the density of the lamellar sensory corpuscles along the deep vessels by measuring the number of observed lamellar sensory corpuscles within the observed vessel length (cm).

2.1.3. Immunohistochemical analysis

We analyzed the structure of identified lamellar sensory corpuscles by immunohistochemistry using antisera against the inner core and neurite markers in PCs and compared the structure of the identified lamellar sensory corpuscles with that of previously reported PCs (García‐Suárez et al., 2010; Morishita et al., 2018; Pawson et al., 2000; Vega et al., 1996). We used three types of markers for immunohistochemical staining: S100 as a marker of Schwann cells that constitute the inner core of PCs (Iwanaga et al., 1982), neurofilament H (NF‐H) as a marker of neurites of myelinated nerves (Iwanaga et al., 1982), and PGP9.5 as a marker of neurites of peripheral nerves (Dalsgaard et al., 1989).

After de‐paraffinization and rehydration, sections were incubated in 0.1 M citrate buffer (pH 6.0) for antigen retrieval (15 min, 98°C). Sections were blocked in phosphate buffer saline (PBS) containing 5% normal donkey serum for 1 h at room temperature. They were incubated with primary antibodies, i.e., anti‐S100 antibodies (1:2000; DakoCytomation, Cat# 20311, RRID: AB_10013383), anti‐NF‐H antibodies (1:200; Developmental Studies Hybridoma Bank, Cat# rt‐97, RRID: AB_528399), or anti‐PGP9.5 antibodies (1:200; abcam, Cat# ab108986, RRID: AB_10891773), overnight at 4°C. For the negative control, the sections were incubated with normal rabbit IgG (1:200; R&D Systems. Inc., Cat# AB‐105‐C, RRID: AB_354266). After washing with phosphate‐buffered saline supplemented with 0.05% Tween‐20 (PBS‐T), sections were incubated with secondary antibodies, i.e., biotinylated anti‐mouse IgG antibodies (1:500; abcam, Cat# ab5886, RRID: AB_954791) or biotinylated anti‐rabbit IgG antibodies (1:500; Vector Laboratories, Cat# BA‐1100, RRID: AB_2336201), for 1 h at room temperature. After a subsequent wash with PBS‐T, sections were incubated with alkaline phosphatase conjugated streptavidin (Boehringer Ingelheim, Ingelheim am Rhein, Cat# 60660, RRID: AB_10099593). Subsequently, sections were washed with PBS‐T and incubated with 0.1 M Tris‐HCl (pH 9.5) buffer containing 50 mM MgCl2. Signals were detected with 450 μg/ml nitro blue tetrazolium chloride and 175 μg/ml 5‐bromo‐4 chloro‐3‐indolylphosphate toluidine salt in 0.1 M Tris‐HCl (pH 9.5) buffer containing 50 mM MgCl2. Thereafter, sections were dehydrated and mounted with Vector Mounting Medium (H1400, Vector Laboratories) or G‐Mount (GM‐01, GenoStaff). Stained sections were observed using an optical microscope equipped with the CCD camera (Olympus BX51 and DP73, Olympus Corp.).

Double immunofluorescence staining was performed as described above to block with 5% normal donkey serum. Sections were incubated with diluted primary antibodies, i.e., anti‐S100 antibodies (1:2000) and anti‐NF‐H antibodies (1:200), overnight at 4°C and then washed with PBS‐T. Subsequently, sections were incubated with Alexa Fluor 488‐conjugated anti‐rabbit IgG antibodies (1:1000; Jackson ImmunoResearch, Cat# 711‐547‐003, RRID: AB_2340620) and Cy3‐conjugated donkey anti‐mouse IgG antibodies (1:1000; Jackson ImmunoResearch, Cat# 715‐165‐150, RRID: AB_2340813) for 1.5 h at room temperature and then washed with PBS‐T. Later, sections were mounted with Vector Mounting Medium (H1400). Immunofluorescence images were acquired with a confocal laser scanning microscope (LSM710, Zeiss).

2.2. Analysis of the relationship between korotkoff sound and sensation of vibration

We examined the relationship between vascular sound and pulsating sensation in five (four males and one female) healthy adult humans. The participants, who were researchers of Hyogo College of Medicine, provided written informed consent. This study was approved by the Ethics Review Board of the Hyogo College of Medicine (No. 3320). We confirmed the normal range of the vibration sensation in the upper limb using a 256 Hz tuning fork (SOT‐8641, SAKAImed); subsequently, we wrapped a manchette around the subject's upper arm and placed the electronic stethoscope (Littmann Electronic Stethoscope Model 3200, 3 M Company) in front of the upper arm at the distal side of the manchette. After air was blown into the manchette to temporarily stop the blood flow in the upper arm, the air in the manchette was slowly evacuated and blood flow was gradually resumed. The vascular sound (Korotkoff sound) was recorded using an electronic stethoscope. The starting and end points of the time during which the subject felt a pulse were also recorded. The examination was conducted three times per subject. One trial was missing since the sound file was not recorded. We converted the recorded vascular sound to spectrogram using Audacity® Cross‐platform Sound Editor 2.3.2. Audacity® software is copyright© 1999–2020 Audacity Team. The name Audacity® is a registered trademark of Dominic Mazzoni. (RRID: SCR_007198). The waveform of the vascular sound, depicted with time in the horizontal axis and relative amplitude in the vertical axis, determined the maximum input including noise during the recording as zero. We applied both a high pass (150.0 Hz, attenuation 48 dB) and low pass filter (400.0 Hz, attenuation 48 dB) to visualize sound levels of the frequencies to which PCs are sensitive. The recorded maximum sound amplitude was chosen as 0 dB. We defined definitive vascular sounds those with amplitude within the range from the peak of a succession of beating signals to minus 20 dB of the peak amplitude. This range was highlighted in orange in Figure 5. The time span during the definite vascular sounds was compared with the time when the subject felt vibrations.

FIGURE 5.

FIGURE 5

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Waveform of vascular sounds recorded at the upper arm during blood‐pressure measurements filtered between 150 and 400 Hz. The vertical axis shows amplitude (dB) of sound waves that is proportional to sound intensity. The horizontal axis shows time. The start and the end labeled arrows indicate the beginning and end of the pulsating sensation that the subject pointed out. The strong labeled arrow indicates the timing when the subject felt the strong sensation in the upper arm. Recorded waveform of vascular sounds within the orange range were defined as definite vascular sounds. The figure excludes data after vascular sounds disappeared due to excessive noise owing to stethoscope removal

2.3. Statistical analysis

Student t test was used for statistical comparisons between the mean values of the estimated width and length of identified lamellar sensory corpuscles. Differences with p value < 0.05 were considered statistically significant.

3. RESULTS

3.1. Lamellar sensory corpuscles localize in the vascular sheath of the deep vessels and in the connective tissue surrounding the vascular sheath

We identified 34 lamellar sensory corpuscles from the connective tissue around the deep vessels from the branching of the subscapular artery to the bifurcation of the ulnar and radial arteries in the right upper arm of one cadaver. We could clearly identify lamellar sensory corpuscles in the connective tissue around the deep vessels (Figure 1). Several lamellar sensory corpuscles were observed in the vascular sheath, which is the dense connective tissue that wraps arteries and veins (Figure 1a,b), and some other lamellar sensory corpuscles were located in the loose connective tissues surrounding the vascular sheath and the median nerve (Figure 1c,d). In this study, we defined lamellar sensory corpuscles as perivascular lamellar sensory corpuscles (pvLC) and extravascular‐sheath lamellar sensory corpuscles (exLC). The pvLC is defined as a lamellar sensory corpuscle within the vascular sheath. The exLC is defined as a lamellar sensory corpuscle localized in the connective tissue outside the vascular sheath. We identified 11 pvLCs and 18 exLCs in this study. However, we could not classify 5 LCs as pvLCs or exLCs because the position of the lamellar sensory corpuscles with relation to the vascular sheath was not clear.

FIGURE 1.

FIGURE 1

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Localization of lamellar sensory corpuscles in the internal brachium. (a) Image of a lamellar sensory corpuscle within the vascular sheath of the brachial artery and vein (pvLC). A rectangle indicates the region shown in (b). (b) High‐magnification image of a pvLC. (c) Image of a lamellar sensory corpuscle located in the loose connective tissue surrounding the vascular sheath (exLC). A rectangle indicates the region shown in (d). (d) High‐magnification image of an exLC. The upper side of the figure indicated the dorsal side. Scale bar: 1 mm (a, c), and 100 μm (b, d). D: dorsal, V: ventral, I: inner, O: outer, BA: brachial artery, BV: brachial vein

3.2. Lamellar sensory corpuscles accumulate near the bifurcation of the ulnar and radial arteries

Both types of lamellar sensory corpuscles—pvLC and exLC—were unevenly distributed along the blood vessel, while several were localized at the distal brachial artery near the bifurcation of the radial and ulnar arteries, with few located in the middle area of the brachial artery (Figure 2: density of lamellar sensory corpuscles; 10/2.5 cm near the elbow region and 0/2.48 cm in middle area). In the proximal region, several lamellar sensory corpuscles were localized near the branch of profunda brachii artery. The accumulation of the lamellar sensory corpuscles near the elbow was also observed in the other cadaver and the left side of the upper arm (13/3.0 cm near the bifurcation of the radial and ulnar arteries and 1/3.0 cm in middle area of the left upper arms of the same cadaver shown in Figure 2; 12/3.0 cm (right) and 11/3.0 cm (left) near the bifurcation of the radial and ulnar arteries and 2/2.28 cm (right) and 0/2.0 cm (left) in middle area of upper arm of the other cadaver). We investigated the position of lamellar sensory corpuscles in relation to the vessel and found that 64% (7/11) and 36% (4/11) of pvLCs were distributed on the ventral and dorsal sides of the brachial artery and vein, respectively (Figure 2a‐d, a´‐d´).

FIGURE 2.

FIGURE 2

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Distribution of lamellar sensory corpuscles. (a‐h) (a´‐h´) Images of lamellar sensory corpuscles stained with hematoxylin/eosin. (a‐d) pvLC. (e‐h) exLC. Squares indicate magnified region in a´‐h´. (a´‐d´) Magnified pvLC. (e´‐h´) Magnified exLC. The upper side of the figure indicated the dorsal side. The lamellar sensory corpuscle of (a, a´) has been shown in Figure1. a, b. Scale bar: 500 μm (a‐h), 50 μm (a´‐h´). D: dorsal, V: ventral, I: inner, O: outer, BA: brachial artery, BV: brachial vein, RA: radial artery, RV: radial vein. (i) Distribution of lamellar sensory corpuscles around the deep vessels in the upper arm. Several branches of the artery are shown. ● pvLC ▲ exLC ■ lamellar sensory corpuscles not identified as pvLC or exLC

3.3. Sizes of identified lamellar sensory corpuscles were similar to that of PCs around the femoral artery

To compare the size of pvLCs and exLCs, we inferred sizes of lamellar sensory corpuscles using reconstitution of serial sections (Figure S1). Since the lamellar sensory corpuscles were practically cut in the short‐axis direction, we assumed that they laid parallel to the blood vessel. We estimated the length of lamellar sensory corpuscles from the number of serial sections, and the maximum diameter of one lamellar sensory corpuscle in a section as the width of the lamellar sensory corpuscles. Since 5 lamellar sensory corpuscles were located on sections’ edges, their size could not be estimated. We found no significant differences in width (pvLCs, n = 8; exLCs, n = 14, p‐value = 0.378) and length (pvLCs, n = 8; exLCs, n = 14; p‐value = 0.512) between pvLCs and exLCs (Table 1). This estimated size of lamellar sensory corpuscles is similar to the previously reported size of PCs around the femoral artery (Morishita et al., 2018).

TABLE 1.

Estimated width and length of identified lamellar sensory corpuscles

Total pvLCs exLCs
Width Number 22 8 14
Mean (µm) ±SE 278 ± 37 235 ± 33 303 ± 53
Range (µm) 92–807 107–403 92–807
Length Number 22 8 14
Mean (µm) ±SE 636 ± 93 718 ± 169 590 ± 108
Range (µm) 140–1540 140–1400 140–1540
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Abbreviations: SE, standard error.

3.4. Identified lamellar sensory corpuscles and reported PCs have the same structure

We investigated the structure of the lamellar sensory corpuscles. Lamellar sensory corpuscles had a S100‐positive region at the central area (Figure 3a,e, Figure S2). NF‐H positive region were localized at the central area of lamellar sensory corpuscle (Figure 3b,f). The staining pattern of PGP9.5 (Figure 3c,g, Figure S2) was also observed at the central area of lamellar sensory corpuscles. We examined the relationship of S100 and NF‐H positive region using double immunofluorescence analysis (Figure 4) and observed that the S100‐positive area surrounded the NF‐H‐positive region. These results indicate that the lamellar sensory corpuscles around deep vessels of the upper arm have the same structure as PCs in other tissues.

FIGURE 3.

FIGURE 3

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Immunohistochemical analysis of lamellar sensory corpuscle. (a‐h) Localization of S100 (a, e), NF‐H (b, f), and PGP9.5 (c, g) in pvLC. Squares in (a‐d) indicate the regions shown in (e‐h). Scale bar: 100 μm (a‐d), and 20 μm (e‐h)

FIGURE 4.

FIGURE 4

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Double immunofluorescence analysis of S100 and NF‐H in the lamellar sensory corpuscle showing the same staining image of the PC. (a) Low magnification image of lamellar sensory corpuscle. Squares indicate the region shown in (b). (b) High‐magnification image of lamellar sensory corpuscle. Scale bar: 200 μm (a), 20 μm (b)

3.5. Sound by pressing brachial artery related to pulsating sensation

We examined the relationship between vascular sound and pulsating sensation in five subjects who felt a knocking‐like pulsating sensation when the upper arm was under the pressure of the manchette of a sphygmomanometer. The pulsating sensation of the upper arm became stronger and then gradually weakened, disappearing along with the pressure reduction. Two subjects reflected on the difficulty to be aware of the beginning of the pulsating sensation. In 5 of 14 trials in this study, the timing of the strong knocking‐like pulsating sensation in the upper arm are within the duration of the recording of strong vascular sounds with a frequency of around 200 Hz (Figure 5, Figure S3). In the remaining nine trials, the subjects did not mention the strength of the pulsating sensation. In 8 of 14 trials, the time when the definite vascular sounds were completely detected included the time when subjects felt the vibration (Figure 5). The remaining six trials showed that the beginning of the definite vascular sounds preceded the time when subjects sensed the vibration, and that the end of the definite vascular sounds preceded the timing when subjects stopped feeling the vibration.

4. DISCUSSION

In this study, we investigated the materials derived from two aged male Japanese cadavers, which had been donated for education. Furthermore, any analysis related to age in Japan is difficult due to the aging society. We have identified 34 lamellar sensory corpuscles from transverse sections of deep artery and veins from the branching of the subscapular artery to the bifurcation of the ulnar and radial arteries using the serial sectioning of the right upper arm of one cadaver. We also found similar distribution tendency of the lamellar sensory corpuscles in the left upper arm of the same cadaver and both side of the upper arm of the other cadaver, possibly illustrating the distribution of the lamellar sensory corpuscles long the deep vessels in the human upper arm. Since PCs are distributed in the muscular facia (Benjamin, 2009; Stecco et al., 2006), we supposed that the exLCs found in this study were associated with the medial intermuscular septum of the arm.

The identified lamellar sensory corpuscles and the previously reported PCs had the same structure (Bell et al., 1994; García‐Suárez et al., 2010) based on the immunohistochemical analysis. The staining of PGP9.5 and NF‐H in Figure 3 shows the complex structure in the inner core of the neurite, which is also shown by the staining. As human Pacinian corpuscles have multiple axons and a branched axon (García‐Suárez et al., 2010; Ide et al., 1987), our results indicate that our identified lamellar sensory corpuscles had multiple axons or complex branched axon. Based on our histological analysis, the identified lamellar sensory corpuscles sense vibration similar to PCs in other tissues. This finding is supported by a previous study which showed that, in cats, the mesenteric and tactile PCs localized in the skin share anatomical and physiological similarity (Pawson et al., 2008).

Our results show that seven of eleven pvLCs were distributed on the ventral side of blood vessels; however, Morishita et al. (2018) has reported that 66.6% of PCs around the femoral artery were localized on the dorsal side, which is opposite to our finding. Since the flexion side of the elbow joint is the ventral side and the flexion side of the knee joint is the dorsal side, the PCs in the vascular sheath of limb vessels were predominantly located on the flexion side of the blood vessel. The estimated size of lamellar sensory corpuscles was almost within the range of previously reported PCs around the femoral artery, 0.42–2.66 mm long and 0.12–0.43 mm wide (Morishita et al., 2018). The average size of identified lamellar sensory corpuscles was smaller than that of PCs in the hands, 0.66–3.5 mm long and 0.30–4.84 mm wide (Stark et al., 1998). As the mechanical model indicates that the frequency sensitivity range depends on the PCs size (Quindlen et al., 2016), we believe that PCs around the vessels detect lower frequency vibrations than PCs in the hand.

The maximum sensitivity of PCs ranges between 150 and 300 Hz (Bolanowsky & Verrillo, 1982; Pawson et al., 2008; Sato, 1961). In this study, the duration of strong knocking‐like pulsating sensation in the upper arm almost coincided with the duration of recording strong vascular sound showing a frequency of approximately 200 Hz. Kortokoff sounds are thought to be derived from various types of fluid‐induced vibrations including turbulence or cavitation (Babbs, 2015; Chungcharoen, 1964; Gupta et al., 1975; McCucheon et al., 1967; Ur & Gordon, 1970). Therefore, what subjects felt was possibly derived from the vascular vibration detected by lamellar sensory corpuscles around deep vessels. PCs in a cat's knee joint and mesentery fire in synchrony with the arterial pulse (Burgess & Clark, 1969; Gammon & Bronk, 1935; Tuttle & McCleary, 1974; Yamashita & Buendia, 1968). We believed the identified lamellar sensory corpuscles recognize the vascular vibration as the pulsating sensation.

When a limb flexes, an artery in the limb is bent and compressed (MacTaggart et al., 2014) thereby causing a turbulent blood flow in the vessel around the bending portion (Wood et al., 2006), which in turn may cause an increase or decrease of the pulsative blood movement. The threshold of PCs has been reported to increase when the receptor is stimulated along the vertical axis and to decrease when the PC is stimulated along the transverse axis of the nerve ending (Il'inskii et al., 1968). Thus, it is expected that the lamellar sensory corpuscles that exist parallel to blood vessels respond effectively to mechanical stimulation from blood vessels along the transverse axes of lamellar sensory corpuscles. The distribution of lamellar sensory corpuscles, and their characteristics, indicate that, around blood vessels, they sense changes in pulsating vibration due to flexion/extension of the elbow and shoulder joints. However, participants expressed that the beginning and end of the pulsating sensation were difficult to recognize with respect to the vascular sound; we observed that several of them did not sense the pulsation until almost the maximum vascular sounds. In addition, we scarcely recognize alterations of blood vessel vibrations in usual activities. These observations indicate that the sensation of vascular vibration is not usually recognized by the conscious mind, even though cutaneous and joint receptors are involved in the detection of limb position (Collins et al., 2005; Ferrell et al., 1987; Hogervorst & Brand, 1998; Macefield et al., 1990). We considered that the PCs around the large blood vessels are involved in a kind of bathyesthesia not recognized by the conscious mind during usual activities. Although demonstrating the direct relationship between the activation of deeply situated PCs in the human arm and arteries’ pulsation using an electrophysiological approach is challenging due to ethical regulations, previous reports showing that cat's PCs fire in synchrony with the arterial pulse (Burgess & Clark, 1969; Gammon & Bronk, 1935; Tuttle & McCleary, 1974; Yamashita & Buendia, 1968) support our hypothesis.

In this study, we reported the detailed distribution of deeply located PCs in the human upper arm. PCs accumulated near the elbow around the deep blood vessels that bend at the elbow flexion, indicating their role in the detection of blood flow alterations at flexion and extension of the elbow.

5. DATA SHARING

The data that support the findings of this study are available from the corresponding author upon reasonable request.

AUTHOR CONTRIBUTIONS

HY and SM designed the study. YO, HH, SM, YM, SKO acquired the samples. YO, HH, SM, YM, and HY acquired the data. YO, YM, and HY analyzed the data. YO performed the statistical analysis. YO and HY wrote the initial draft. All authors approved the final version of the manuscript.

Supporting information

Fig S1

Click here for additional data file. (745.4KB, tif)

Fig S2

Click here for additional data file. (5.8MB, tif)

Fig S3

Click here for additional data file. (2.7MB, tif)

ACKNOWLEDGMENTS

We are grateful to Prof. K. Noguchi, Dr. H. Yamanaka, Dr. K. Kobayashi, and Dr. M. Okubo (Anatomy and Neuroscience, Hyogo College of Medicine) for fruitful discussions, Ms. R. Fujimoto (Joint‐Use Research facilities, Hyogo College of Medicine), Ms. S. Tokai, Ms. A. Hasegawa, Mr. K. Gion, and Mr. Y. Wadazumi for technical assistance, and Ms. M. Hatta for secretarial assistance. We thank those who donated their bodies for the advancement of education and research. We would also like to thank Cactus Communications (https://www.editage.jp) for English language editing. This study was partially supported by Hirakata Ryoikuen social welfare corporation.

REFERENCES

  1. Babbs, C.F. (2015) The origin of Korotkoff sounds and the accuracy of auscultatory blood pressure measurements. Journal of the American Society of Hypertension, 9, 935–950.e3. [DOI] [PubMed] [Google Scholar]
  2. Bell, J. , Bolanowski, S. & Holmes, M.H. (1994) The structure and function of Pacinian corpuscles: a review. Progress in Neurobiology, 42, 79–128. [DOI] [PubMed] [Google Scholar]
  3. Benjamin, M. (2009) The fascia of the limbs and back—a review. Journal of Anatomy, 214, 1–18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bolanowski, S.J. & Verrillo, R.T. (1982) Temperature and criterion effects in a somatosensory subsystem: a neurophysiological and psychophysical study. Journal of Neurophysiology, 48, 836–855. [DOI] [PubMed] [Google Scholar]
  5. Burgess, P.R. & Clark, F.J. (1969) Characteristics of knee joint receptors in the cat. The Journal of Physiology, 203, 317–335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chungcharoen, D. (1964) Genesis of Korotkoff sounds. American Journal of Physiology‐Legacy Content, 207, 190–194. [DOI] [PubMed] [Google Scholar]
  7. Collins, D.F. , Refshauge, K.M. , Todd, G. & Gandevia, S.C. (2005) Cutaneous receptors contribute to kinesthesia at the index finger, elbow, and knee. Journal of Neurophysiology, 94, 1699–1706. [DOI] [PubMed] [Google Scholar]
  8. Dalsgaard, C.‐J. , Rydh, M. & Haegerstrand, A. (1989) Cutaneous innervation in man visualized with protein gene product 9.5 (PGP 9.5) antibodies. Histochemistry, 92, 385–390. [DOI] [PubMed] [Google Scholar]
  9. Feito, J. , Cobo, J.L. , Santos‐Briz, A. & Vega, J.A. (2017) Pacinian corpuscles in human lymph nodes. The Anatomical Record, 300, 2233–2238. [DOI] [PubMed] [Google Scholar]
  10. Ferrell, W.R. , Gandevia, S.C. & McCloskey, D.I. (1987) The role of joint receptors in human kinaesthesia when intramuscular receptors cannot contribute. The Journal of Physiology, 386, 63–71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fuller, G. (2010) Limbs: reflexes and sensation. Neurology: An illustrated colour text. In: Fuller, G. & Mark, M. (Eds.). London: Elsevier Churchill Livingstone, pp. 26–27. [Google Scholar]
  12. Gammon, G.D. & Bronk, D.W. (1935) The discharge of impulses from Pacinian corpuscles in the mesentery and its relation to vascular changes. American Journal of Physiology‐Legacy Content, 114, 77–84. [Google Scholar]
  13. García‐Suárez, O. , Calavia, M.G. , Pérez‐Moltó, F.J. et al. (2010) Immunohistochemical profile of human pancreatic pacinian corpuscles. Pancreas, 39, 403–410. [DOI] [PubMed] [Google Scholar]
  14. Gupta, R. , Miller, J.W. , Yoganathan, A.P. , Udwadia, F.E. , Corcoran, W.H. & Kim, B.M. (1975) Spectral analysis of arterial sounds: A noninvasive method of studying arterial disease. Medical and Biological Engineering, 13, 700–705. [DOI] [PubMed] [Google Scholar]
  15. Halata, Z. , Rettig, T. & Schulze, W. (1985) The ultrastructure of sensory nerve endings in the human knee joint capsule. Anatomy and Embryology, 172, 265–275. [DOI] [PubMed] [Google Scholar]
  16. Heidenreich, M. , Lechner, S.G. , Vardanyan, V. et al. (2012) KCNQ4 K+ channels tune mechanoreceptors for normal touch sensation in mouse and man. Nature Neuroscience, 15, 138–145. [DOI] [PubMed] [Google Scholar]
  17. Hogervorst, T. & Brand, R.A. (1998) Current concepts review—mechanoreceptors in joint function. The Journal of Bone and Joint Surgery, 80, 1365–1378. [DOI] [PubMed] [Google Scholar]
  18. Ide, C. , Nitatori, T. & Munger, B.L. (1987) The cytology of human Pacinian corpuscles: Evidence for sprouting of the central axon. Archivum histologicum Japonicum, 50, 363–383. [DOI] [PubMed] [Google Scholar]
  19. Il'inskii, O.b. , Volkova, N.k. & Cherepnov, V.l. , (1968) Structure and function of Pacinian corpuscles. Neuroscience and Behavioral Physiology, 2, 637–643. [Google Scholar]
  20. Iwanaga, T. , Fujita, T. , Takahashi, Y. & Nakajima, T. (1982) Meissner’s and Pacinian corpuscles as studied by immunohistochemistry for S‐100 protein, neuron‐specific enolase and neurofilament protein. Neuroscience Letters, 31, 117–121. [DOI] [PubMed] [Google Scholar]
  21. Johnson, K. (2001) The roles and functions of cutaneous mechanoreceptors. Current Opinion in Neurobiology, 11, 455–461. [DOI] [PubMed] [Google Scholar]
  22. Lechner, S.G. & Lewin, G.R. (2013) Hairy sensation. Physiology, 28, 142–150. [DOI] [PubMed] [Google Scholar]
  23. Macefield, G. , Gandevia, S.C. & Burke, D. (1990) Perceptual responses to microstimulation of single afferents innervating joints, muscles and skin of the human hand. Journal of Physiology, 429, 113–129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. MacTaggart, J.N. , Phillips, N.Y. , Lomneth, C.S. et al. (2014) Three‐dimensional bending, torsion and axial compression of the femoropopliteal artery during limb flexion. Journal of Biomechanics, 47, 2249–2256. [DOI] [PubMed] [Google Scholar]
  25. McCutcheon, E.P. , Rushmer, R.F. , Jacobson, O. & Sandier, H. (1967) Korotkoff sounds: an experimental critique. Circulation Research, 20, 149–161. [DOI] [PubMed] [Google Scholar]
  26. Morishita, S. , Sai, K. , Maeda, S. , Kuwahara‐Otani, S. , Minato, Y. & Yagi, H. (2018) Distribution of Pacini‐like lamellar corpuscles in the vascular sheath of the femoral artery. The Anatomical Record, 301, 1809–1814. [DOI] [PubMed] [Google Scholar]
  27. Pawson, L. , Checkosky, C.M. , Pack, A.K. & Bolanowski, S.J. (2008) Mesenteric and tactile Pacinian corpuscles are anatomically and physiologically comparable. Somatosensory & Motor Research, 25, 194–206. [DOI] [PubMed] [Google Scholar]
  28. Pawson, L. , Slepecky, N.B. & Bolanowski, S.J. (2000) Immunocytochemical identification of proteins within the Pacinian corpuscle. Somatosensory & Motor Research, 17, 159–170. [DOI] [PubMed] [Google Scholar]
  29. Pease, D.C. & Quilliam, T.A. (1957) Electron microscopy of the pacinian corpuscle. The Journal of Biophysical and Biochemical Cytology, 3, 331–342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Quindlen, J.C. , Stolarski, H.K. , Johnson, M.D. & Barocas, V.H. (2016) A multiphysics model of the Pacinian corpuscle. Integrative Biology, 8, 1111–1125. [DOI] [PubMed] [Google Scholar]
  31. Roberts, W.H. (1959) Lamellated corpuscles (Pacinian) in relation to the larger human limb vessels and a comparative study of their distribution in the mesentery. The Anatomical Record, 133, 593–603. [Google Scholar]
  32. Sato, M. (1961) Response of Pacinian corpuscles to sinusoidal vibration. The Journal of Physiology, 159, 391–409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Scheibert, J. , Leurent, S. , Prevost, A. & Debrégeas, G. (2009) The role of fingerprints in the coding of tactile information probed with a biomimetic sensor. Science, 323, 1503–1506. [DOI] [PubMed] [Google Scholar]
  34. Shanthaveerappa, T.R. & Bourne, G.H. (1963) New observations on the structure of the pacinian corpuscle and its relation to the perineural epithelium of peripheral nerves. American Journal of Anatomy, 112, 97–109. [DOI] [PubMed] [Google Scholar]
  35. Stark, B. , Carlstedt, T. , Hallin, R.G. & Risling, M. (1998) Distribution of human Pacinian corpuscles in the hand. A cadaver study. The Journal of Hand Surgery: British & European, 23, 370–372. [DOI] [PubMed] [Google Scholar]
  36. Stecco, C. , Porzionato, A. , Macchi, V. et al. (2006) Histological characteristics of the deep fascia of the upper limb. Italian Journal of Anatomy and Embryology, 111, 105–110. [PubMed] [Google Scholar]
  37. Tuttle, R. & McCleary, M. (1974) Pharmacology of the Pacinian receptor. Archives Internationales de Pharmacodynamie et de Therapie, 208, 213–223. [PubMed] [Google Scholar]
  38. Ur, A. & Gordon, M. (1970) Origin of Korotkoff sounds. American Journal of Physiology‐Legacy Content, 218, 524–529. [DOI] [PubMed] [Google Scholar]
  39. Vega, J.A. , Haro, J.J. & del Valle, M.E. (1996) Immunohistochemistry of human cutaneous Meissner and Pacinian corpuscles. Microscopy Research and Technique, 34, 351–361. [DOI] [PubMed] [Google Scholar]
  40. Verrillo, R.T. (2009) Vibration sense. In Encyclopedia of neuroscience (ed. Binder, M.D. , Hirokawa, N. & Windhorst, U. ), pp. 4253–4257.Berlin, Heidelberg: Springer, Berlin Heidelberg. [Google Scholar]
  41. Wood, N.B. , Zhao, S.Z. , Zambanini, A. et al. (2006) Curvature and tortuosity of the superficial femoral artery: a possible risk factor for peripheral arterial disease. Journal of Applied Physiology, 101, 1412–1418. [DOI] [PubMed] [Google Scholar]
  42. Woollard, H.H. & Weddell, G. (1935) The composition and distribution of vascular nerves in the extremities. Journal of Anatomy, 69, 165–176. [PMC free article] [PubMed] [Google Scholar]
  43. Yamashita, E. & Buendia, N. (1968) Functional relation of Pacinian corpuscle to vascular system. The Tohoku Journal of Experimental Medicine, 96, 119–126. [DOI] [PubMed] [Google Scholar]
  44. Zelená, J. (1978) The development of Pacinian corpuscles. Journal of Neurocytology, 7, 71–91. [DOI] [PubMed] [Google Scholar]
  45. Zimny, M.L. & Wink, C.S. (1991) Neuroreceptors in the tissues of the knee joint. Journal of Electromyography and Kinesiology, 1, 148–157. [DOI] [PubMed] [Google Scholar]

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