Dorsal Hairy Skin Research Articles

Abductor Digiti Minimi Myocutaneous Opponensplasty for Hypoplsatic Thumb: Level 4 Evidence

METHODS An elliptically shaped skin flap is designed on the lateral aspect of hypothenar over ADM muscle avoiding dorsal hairy skin area. ADM myocutaneous island flap is elevated based on the neurovascular branches of the ulnar artery and nerve. An incision along the line connecting radial aspect of MP joint and pisiformis is made over hypoplastic thenar area. The ligamentous insertion of the ADM is detached and the flap is set in the defect created in the thenar area and the detached ligament is weaved into the ligamentous tissue around the radial base of the proximal phalanx of the thumb with an appropriate tension. Three weeks after surgery, the thumb is mobilized. We started this procedure based on our original idea in March 1996 for the Blauth type II hypoplastic thumb. This procedure was applied to 18 hands in 16 cases (8 male and 8 female) by 2010. This series included 7 Blauth type II, 6 type III, 3 type IV (after reconstructive procedures) and 5 type V (after pollicization). The age at operation ranged from 1 year 1 month to 8 years 3 month with an average of 4 years 11 months. The postoperative time was 1 years and 6 months to 14 years 11 months with an averaged of 7 years and 6 months. All of the patients had thumb hypoplasia of different degree on the other side.

TRPC1 contributes to light-touch sensation and mechanical responses in low-threshold cutaneous sensory neurons

The cellular proteins that underlie mechanosensation remain largely enigmatic in mammalian systems. Mechanically sensitive ion channels are thought to distinguish pressure, stretch, and other types of tactile signals in skin. Transient receptor potential canonical 1 (TRPC1) is a candidate mechanically sensitive channel that is expressed in primary afferent sensory neurons. However, its role in the mechanical sensitivity of these neurons is unclear. Here, we investigated TRPC1-dependent responses to both innocuous and noxious mechanical force. Mechanically evoked action potentials in cutaneous myelinated A-fiber and unmyelinated C-fiber neurons were quantified using the ex vivo skin-nerve preparation to record from the saphenous nerve, which terminates in the dorsal hairy skin of the hindpaw. Our data reveal that in TRPC1-deficient mice, mechanically evoked action potentials were decreased by nearly 50% in slowly adapting Aβ-fibers, which largely innervate Merkel cells, and in rapidly adapting Aδ-Down-hair afferent fibers compared with wild-type controls. In contrast, differences were not found in slowly adapting Aδ-mechanoreceptors or unmyelinated C-fibers, which primarily respond to nociceptive stimuli. These results suggest that TRPC1 may be important in the detection of innocuous mechanical force. We concurrently investigated the role of TRPC1 in behavioral responses to mechanical force to the plantar hindpaw skin. For innocuous stimuli, we developed a novel light stroke assay using a "puffed out" cotton swab. Additionally, we used repeated light, presumably innocuous punctate stimuli with a low threshold von Frey filament (0.68 mN). In agreement with our electrophysiological data in light-touch afferents, TRPC1-deficient mice exhibited nearly a 50% decrease in behavioral responses to both the light-stroke and light punctate mechanical assays when compared with wild-type controls. In contrast, TRPC1-deficient mice exhibited normal paw withdrawal response to more intense mechanical stimuli that are typically considered measures of nociceptive behavior.

Local effects of octreotide on glutamate-evoked activation of Aδ and C afferent fibers in rat hairy skin

The aim of the present study was to investigate whether local application of octreotide, an analogue of somatostatin, suppresses the glutamate-evoked activities of Aδ and C primary afferent fibers innervating dorsal hairy skin of the rat in vivo. The single unit activity of Aδ and C afferent fibers was recorded in isolated filaments from the dorsal cutaneous branches of the T9–T12 spinal nerves. Changes in discharge relative to baseline during injection of glutamate (0.3 mM, 10 μL) into the receptive field with pretreatment by octreotide (20 μM, 10 μL) were compared with injection after pretreatment with normal saline. Most of Aδ fibers (21/27, 78%) and C fibers (21/26, 81%) in the dorsal cutaneous branches were significantly activated by local injection of glutamate following saline injection. The mean discharge rates increased from 2.39 ± 0.30 and 2.42 ± 0.37 impulses/min to 12.79 ± 2.04 and 13.56 ± 2.56 impulses/min during injection of glutamate for Aδ and C fibers, respectively. After octreotide pretreatment group, glutamate increased the mean discharge rates from 1.93 ± 0.38 and 2.25 ± 0.29 impulses/min to 6.11 ± 0.9 and 6.31 ± 1.18 impulses/min in Aδ fibers and C fibers, respectively. The discharge rates during injection of glutamate after octreotide pretreatment were significantly lower than after normal saline pretreatment. The suppressive effect of octreotide was reversed by the somatostatin receptor antagonist cyclo-somatostatin. These results suggest that interactions between excitatory amino acid and inhibitory neuropeptides may contribute to sensory signaling in the peripheral nervous system.

Tonic inhibition of somatostatin on C and Aδ afferent fibers in rat dorsal skin in vivo

The purpose of this study was to investigate the effect of somatostatin (SST) in peripheral nerve terminals using local application of the SST receptor (SSTR) antagonist cyclo-somatostatin (c-SOM) injected into the receptive fields of cutaneous afferent fibers innervating the dorsal hairy skin in anesthetized rats. Single unit activity was recorded in teased filaments from the dorsal cutaneous nerve branch. Recordings were obtained from 206 primary afferent fibers. They were classified as C ( n = 70), Aδ ( n = 84) or Aβ ( n = 52) fibers based upon their conduction velocity. For C and Aδ fibers, mean discharge rate increased and mechanical threshold decreased significantly to 10 μL of 12.8 and 128 μM injected subcutaneously, but not to 0.128 and 1.28 μM c-SOM injection. For Aβ fibers, no dose of c-SOM changed their discharge rate or their mechanical sensitivity. In control experiments, injection of normal saline (NS) had no effect on any of the units tested. Octreotide (20 μM, 10 μL), an SSTR agonist, successfully reversed the increase in discharge rates and the decrease in mechanical thresholds in C and Aδ fibers when it was pre-administrated into the receptive field before c-SOM injection. These results provide evidence that somatostatin tonically inhibits the peripheral nerve terminals of small-diameter cutaneous afferent fibers.

ELECTROPHYSIOLOGICAL EVIDENCE FOR THE INTERACTION OF SUBSTANCE P AND GLUTAMATE ON Aδ AND C AFFERENT FIBRE ACTIVITY IN RAT HAIRY SKIN

1. The purpose of the present study was to investigate whether there was a cooperative interaction between substance P (SP) and glutamate (GLU) administered subcutaneously on Adelta and C primary afferent fibre activity in dorsal hairy skin of the rat in vivo. The single unit activities of Adelta and C afferent fibres were recorded by isolation of fibre filaments from the dorsal cutaneous nerve branches and the effects of subcutaneous injections of low doses of SP, GLU and SP + GLU on activity were determined. 2. Sub-threshold doses of SP (1 micro mol/L, 10 microL) administered subcutaneously into the dorsal hairy skin had no effect on the afferent discharges of either Adelta or C units. 3. The afferent discharges of 35% (11/31) of Adelta fibres and 33% (6/18) of C fibres were increased by local injection of the submaximal doses of GLU (10 micro mol/L, 10 microL) into the receptive fields. 4. The GLU-induced excitatory response was significantly enhanced by coinjection of subthreshold doses of SP. The mean discharge rates of Adelta fibres and C fibres were increased from 5.84 +/- 1.54 and 5.02 +/- 2.65 impulses/min to 19.91 +/- 4.35 and 17.58 +/- 5.59 impulses/min, respectively, whereas the excitatory proportions of Adelta and C fibres were increased from 35 and 33% to 84 and 83%, respectively. The duration of the excitation for Adelta fibres and C fibres was also significantly increased after coinjection of SP + GLU compared with that observed when either substance was given alone. 5. The present study provides electrophysiological evidence for an interaction between receptors for SP and GLU on the fine fibres activities in rat hairy skin, which may be involved in the mechanisms of hyperalgesia.

Activation and sensitization of C and Aδ afferent fibers mediated by P2X receptors in rat dorsal skin

The present study investigated the activation and sensitization effects of local injection of P2X receptor agonist α,β-methylene ATP (αβ-meATP) into the receptive fields of afferent fibers innervating dorsal hairy skin in anesthetized rats. Single unit activities of afferent fibers were recorded by means of isolation of the fiber filaments from the dorsal cutaneous nerve branch. A total of 237 fibers were obtained. Of these, 67 were classed as C fibers, 104 as Aδ fibers and 66 as Aβ fibers. When αβ-meATP (0.1–100 μM, 10 μl) was injected subcutaneously into the receptive fields of these units, C and Aδ fibers demonstrated a dose-related increase in the discharge rates of the response. The activated proportion of C and Aδ fibers with a response to the drug also increased with dose. However, Aβ fibers did not exhibit significant activation. Furthermore, injection of αβ-meATP (10 μl) at a concentration of 100 μM resulted in a significant decrease of mechanical thresholds in C and Aδ fibers compared with pre-injection baseline ( P < 0.05). In control experiments, injection of the vehicle phosphate-buffered saline (PBS, 10 μl) had no effect on all units tested. αβ-meATP (100 μM, 10 μl) followed by pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), a P2X receptor antagonist, successfully blocked the activation and sensitization effects of αβ-meATP on C and Aδ fibers tested. These results suggest that peripheral P2X receptors are involved in mediating peripheral excitation of C and Aδ fibers.

Local application of morphine suppresses glutamate-evoked activities of C and Aδ afferent fibers in rat hairy skin

Behavior studies have demonstrated that local application of morphine in peripheral tissues resulted in a significant antinociceptive effect, but there has been no electrophysiological evidence to support the peripheral mechanism of opioid antinociception. The purpose of the present study was to investigate whether local application of morphine suppressed the glutamate-evoked activities of C and Aδ primary afferent fibers in dorsal hairy skin of rat in vivo. The single unit activities of the C and Aδ afferent fibers were recorded by means of isolation of the fiber filaments from the dorsal cutaneous nerve branches, and the effects of glutamate and glutamate plus morphine injected into the receptive field on these activities were determined. The results revealed that most of the C and Aδ fibers were excited significantly by local injection of glutamate (0.3 mM), with the percentage being 81% (22/27, for C fibers) and 73% (36/49, for Aδ fibers), respectively. The glutamate-induced excitatory response was significantly suppressed by co-injection of morphine (1.0 mM). The mean discharge rates of C fibers and Aδ fibers decreased from 28.96 ± 6.85, 28.99 ± 3.79 impulses/min to 4.40 ± 1.76, 2.72 ± 0.71 impulses/min, respectively. The suppressing effect of morphine was reversed by pretreatment with opioid receptor antagonist naloxone (1.0 mM). These findings suggest that local application of morphine can suppress the glutamate-evoked activities of the fine fibers in rat hairy skin and thus provide an electrophysiological evidence for peripheral antinociception of opioids.

Weight bearing of the limb as a confounding factor in assessment of mechanical allodynia in the rat

Effect of weight bearing of the hindlimbs on the assessment of mechanically-induced hindlimb withdrawal threshold was determined in intact rats and in rats with various pathophysiological conditions causing allodynia or hyperalgesia. Hindlimb withdrawal was elicited by applying a series of calibrated monofilaments to the plantar or the dorsal surface of the paw. During testing the rat was either in a restraint tube with hindlimbs hanging semi-extended without weight bearing or it was standing on a metal grid (bearing its own weight). In intact rats, the withdrawal thresholds were significantly lower when the stimulus site was the dorsal hairy skin rather than the plantar glabrous skin. Also, thresholds were significantly lower when the hindlimbs were not bearing weight. Following carrageenan-induced unilateral inflammation of the plantar paw or a tibial nerve cut there was a marked threshold decrease to test stimuli applied to plantar or dorsal paw, respectively, ipsilateral to the pathological condition in standing rats. However, when the hindlimbs were not weight bearing the unilateral threshold decrease was markedly attenuated (carrageenan-treated rats) or completely abolished (tibial cut). In contrast, in rats with a unilateral spinal nerve ligation the threshold decrease ipsilateral to the nerve lesion was highly significant independent of the weight bearing of the hindlimbs. The results indicate that weight bearing of hindlimbs is an important confounding factor in the assessment of tactile allodynia in rats.

Comparison of Immunohistochemical and Functional Reinnervation of Skin and Muscle after Peripheral Nerve Injury

In order to investigate the usefulness of immunohistochemical detection of regenerating axons as a correlate of functional recovery, reinnervation of mouse foot pads, hairy skin, and muscle were studied at several intervals along 3 months after sciatic nerve crush using immunohistochemical markers PGP 9.5 and CGRP. These histological results were compared with functional recovery of sweat glands (SGs), plantar muscles, and pain sensibility. One week after nerve injury all neural functions were abolished in the operated hindpaw of all mice, no CGRP-immunoreactive (-ir) fibers were seen in the samples studied, while PGP 9.5 immunofluorescence remained at dim levels within nerve trunks, but disappeared from terminal innervation. The first PGP 9.5- and CGRP-ir regenerating fibers were seen at 15–16 days postoperation (dpo) in dermal nerve trunks of dorsal hairy skin and some days later in dermal trunks of foot pads. Regenerating nerve fibers progressed along the periphery of the dermis reinnervating the different dermal appendages. At 25 dpo all target organs were reinnervated. The first SGs activated by pilocarpine reappeared by 16 dpo and increased in number to 88% of control counts. Nociceptive responses reappeared at 17 dpo and reached 100% of control values. The first PGP immunofluorescence in neuromuscular junctions was seen at 16 dpo, while the first muscle action potentials were recorded at 19 dpo, and the potentials amplitude increased to 66% of controls. Good correlations were found between morphological and functional results of reinnervation. However, the density and distribution of nerve profiles in the tissues studied did not reach normal levels, while neural functions conveyed by small fibers reached levels similar to controls.

Relationship between representation of hindpaw and hindpaw barrel subfield (HBS) in layer IV of rat somatosensory cortex.

We describe the organization of the hindpaw barrel subfield (HBS) in layer IV of rat somatosensory cortex (SI) and relate this organization to the representation of the hindpaw. The ovoid-shaped, HBS is oriented anterior to posterior and comprises barrels and barrel-like structures, the most prominent of which consist of at least five anteriorly-located elongated barrel bands. Posterior to these elongated bands is a cluster of four barrels. Two additional barrels are found, one lateral, the other medial. The lateral border is formed by a nearly continuous band that overlaps portions of the anterior elongated bands and posterior barrels. The HBS shows considerable variability in size and shape; nevertheless, the overall pattern reflects a common plan of organization. Electrophysiological mapping confirmed that hindpaw representation is somatotopically organized. The glabrous toes are represented anteriorly, the pads posteriorly, and the dorsal hairy skin of the toes and hindpaw laterally. By aligning physiological and morphological (HBS) maps according to lesion sites, our data suggest that the elongated anteriorly-located barrel bands represent the hindpaw toes, the four toe pads are represented immediately posterior followed by barrels representing the plantar pads. The representations of dorsal hairy skin of toe and dorsal hindpaw form the lateral border; the heel and ankle are represented most posterior. We interpret our findings as support that individual barrels in the HBS are associated with discrete regions of the hindpaw; however, the precise relationship of structure and function reported between the vibrissae and posteromedial barrel subfield (PMBSF) and between the forepaw and the forepaw barrel subfield (FBS) were not observed.

Fiber composition of the lateral plantar and superficial peroneal nerves in the rat foot

This study examines the fiber composition of two nerves projecting to the rat hindpaw: the lateral plantar nerve (LPN), which innervates plantar glabrous skin and some plantar muscles, and the foot branch of the superficial peroneal nerve (fSPN), which projects to dorsal hairy skin. The LPN contains 872 (33%) myelinated axons with a size range of 1-7 microns and a peak at 4 microns. Some 200 of the myelinated axons are muscle efferents. There are 1,969 (67%) C-fibers. After neonatal capsaicin treatment, the number of C-fibers in the LPN is 61% below the normal level, but it is not significantly different from control levels after chemical sympathectomy with guanethidine. The fSPN is composed of 470 (20%) myelinated axons with a size range similar to that in the LPN. Virtually all myelinated fibers are sensory. There are 1,791 (80%) C-fibers. In neonatally capsaicin-treated animals, the occurrence of C-fibers is 65% below control levels. In chemically sympathectomized animals, the number of C-fibers in the fSPN is normal. This description of the fiber composition of the LPN and the fSPN in the rat provides a basis for future experimental studies.

Functional subdivisions representing different finger regions in area 3 of the first somatosensory cortex of the conscious monkey

The representation of fingers in the first somatosensory cortex was studied in conscious monkeys by recording single neuronal activity, and the following results were obtained: (1) In area 3a, most neurons responded to joint manipulation or other types of deep stimuli. The representation of five fingers was somatotopically arranged. (2) In area 3b, 77.7% and 20.9% of identified neurons responded to cutaneous and deep stimuli respectively. (3) Neurons responding to light mechanical stimuli and with receptive fields on the distal finger segment were found in the most anterior part of area 3b while those responding better to specific mechanical stimuli, such as rubbing, scraping, pinching, tapping, etc. of finger glabrous skin, were found in the more posterior part. The representation of the five fingers was somatotopically arranged. (4) Neurons responding to light or specific mechanical stimulation of the dorsal hairy skin of fingers were found in the posterior part of area 3b. The independent somatotopic representation of four fingers was recognized within this region. (5) Neurons responding to mechanical stimulation of the palmar skin were found in two separate regions, the medial one for the ulnar half and the lateral one for the radial half of the palm. (6) These results indicate that the representation of fingers in areas 3a and 3b of the conscious monkey is divided into multiple somatotopic subdivisions each representing a functional region of the hand and fingers. (7) Neurons with multi-finger receptive fields were occasionally found in area 3b, mostly in layer VI. Some of them had inhibitory receptive fields. Multifinger type receptive fields were more commonly found in area 1.