Types Of Nerve Fibers Research Articles

PD36-10 MICROANATOMY AND INNERVATION PATTERNS OF THE SPERMATIC CORD IN HUMANS

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research II1 Apr 2015PD36-10 MICROANATOMY AND INNERVATION PATTERNS OF THE SPERMATIC CORD IN HUMANS Koji Shiraishi, Shintaro Oka, and Hideyasu Matsuyama Koji ShiraishiKoji Shiraishi More articles by this author , Shintaro OkaShintaro Oka More articles by this author , and Hideyasu MatsuyamaHideyasu Matsuyama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2259AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Understanding of the spermatic microanatomy is important during the microsurgical denervation of the spermatic cord (MDSC) and varicocelectomy. Anatomical information regarding spermatic vessels has been well documented; however, the locations of the lymphatics and nerves and the types of nerve fibers have been poorly investigated. The purposes of this study are to document the distribution of lymphatics and nerves and identify the types of nerve fibers in the human spermatic cord. METHODS Between August 2013 and August 2014, a total of 33 men (17 to 43 years old) underwent microsurgical inguinal varicocelectomy (n=23) or MDSC (n=10) and agreed with the purpose of this study. The outer half of the spermatic fascia was resected intraoperatively to 2 cm, fixed with formalin and immunostained with antibodies against a lymphatic marker D2-40, a pan-neuronal marker PGP9.5, a sympathetic marker tyrosine hydroxylase (TH), a parasympathetic marker vasoactive intestinal polypeptide (VIP), and a sensory nociceptor marker calcitonin gene-related peptide (CGRP). The innervation density was examined in patients subdivided according to the presence of orchalgia. The same analyses were performed using the whole sections of the spermatic cord that were obtained from 10 patients with testicular cancer who had undergone an orchiectomy. RESULTS The spermatic fascia was composed of mainly smooth muscle fibers. The mean number of lymphatics in the spermatic fascia was 0.4, and lymphatics were found in 26% of the men. The majority of lymphatics were localized in the intraspermatic cord. The mean number of nerve fibers that were positive for PGP9.5 in the spermatic fascia was 7.2. Ninety percent of the PGP9.5-positive fibers were also positive for CGRP, and 75% of the fibers were positive for TH but not for VIP. The number of CGRP-positive fibers was significantly higher in men with orchalgia than in men without orchalgia (p<0.05). In the spermatic cord, both PGP9.5- and TH-positive fibers were distributed (mean number: 8.9), and the distribution of the CGRP fibers in the intraspermatic cord was sparse, except for around the vas. CONCLUSIONS The CGRP-positive sensory nerve is considered to be involved in the pathophysiology of chronic orchalgia, and the transection of spermatic fascia and nerve fibers around the vas is extremely important during MDSC. The post-operative scrotal hydrocele may not be a problem if several lymphatics are preserved in the spermatic cord. Sympathetic fibers in the spermatic fascia and cord may contribute to the contraction of spermatic muscle and testicular blood regulation. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e768-e769 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Koji Shiraishi More articles by this author Shintaro Oka More articles by this author Hideyasu Matsuyama More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Skin Biopsy: Emerging Method for Small Nerve Fiber Evaluation

Skin biopsy with investigation of small nerve fiber in human epidermis and dermis has been proven to be a useful method for demonstration of small fiber neuropathy. Quantification of intraepidermal nerve fiber density using anti-Protein Gene Product 9.5 (PGP 9.5) antibody is standardized method to diagnose the small fiber neuropathy. Skin biopsy method also makes it possible to differentiate the type of nerve fibers by using different antibodies. Quantification of dermal structures with different type of nerve fibers could be used to invest pathophysiologic mechanism of diseased state. (Korean J Clin Neurophysiol 2015;17:53-60)

Anatomical basis of female pelvic cavity for nerve sparing radical hysterectomy.

The separation and sparing of the vesical branch of the inferior hypogastric plexus (IHP), to preserve the pelvic autonomic nerve, is critical and difficult in nerve sparing radical hysterectomy. Pelvic local anatomy was performed to provide the necessary anatomical information. Precise pelvic anatomy was performed in 15 adult corpses, and immunohistochemical analysis was carried out on the parametrial tissues of three fresh cadavers to analyze the nerve fiber type and content of the vesical branch of the IHP. The deep uterine vein is located in the upper region of the cardinal ligament (CL), with three to six multiple branches and anatomical variation, including one or two cervical branches, and two to four vesical branches. Three branches were found to be most common (63.3 %). The major distribution of the vesical branch of the IHP is dorsomedial to the middle and inferior vesical veins, with less ventral and lateral distribution. There are more sympathetic fibers than parasympathetic fibers in the vesical branch. There is a region rare of vasculature and nerve between the vaginal lateral margin and the vesical branch. The deep uterine vein is suggested as an anatomical landmark during surgery, to process the CL and preserve the pelvic splanchnic nerves. The middle and inferior vesical veins can be used as the landmark to preserve the vesical branch of the IHP.

A quantitative sensory analysis of peripheral neuropathy in colorectal cancer and its exacerbation by oxaliplatin chemotherapy.

Peripheral neuropathy caused by cytotoxic chemotherapy, especially platins and taxanes, is a widespread problem among cancer survivors that is likely to continue to expand in the future. However, little work to date has focused on understanding this challenge. The goal in this study was to determine the impact of colorectal cancer and cumulative chemotherapeutic dose on sensory function to gain mechanistic insight into the subtypes of primary afferent fibers damaged by chemotherapy. Patients with colorectal cancer underwent quantitative sensory testing before and then prior to each cycle of oxaliplatin. These data were compared with those from 47 age- and sex-matched healthy volunteers. Patients showed significant subclinical deficits in sensory function before any therapy compared with healthy volunteers, and they became more pronounced in patients who received chemotherapy. Sensory modalities that involved large Aβ myelinated fibers and unmyelinated C fibers were most affected by chemotherapy, whereas sensory modalities conveyed by thinly myelinated Aδ fibers were less sensitive to chemotherapy. Patients with baseline sensory deficits went on to develop more symptom complaints during chemotherapy than those who had no baseline deficit. Patients who were tested again 6 to 12 months after chemotherapy presented with the most numbness and pain and also the most pronounced sensory deficits. Our results illuminate a mechanistic connection between the pattern of effects on sensory function and the nerve fiber types that appear to be most vulnerable to chemotherapy-induced toxicity, with implications for how to focus future work to ameloirate risks of peripheral neuropathy.

Monitoring of motor function affection and postural sway in patients with type 2 diabetes mellitus

BackgroundDiabetes is a chronic metabolic disease with impaired glucose tolerance. Diabetic neuropathy affects sensory, autonomic, and motor neurons of the peripheral nervous system so that nearly every type of nerve fiber in the body is vulnerable. ObjectivesEvaluation of variation in motor functions and postural sway in patients with type 2 diabetes mellitus (DM) and comparing the results with those obtained from the control group. This will help in rehabilitation programs for diabetic patients to avoid postural instability and risk of falling. MethodologyForty patients with the diagnosis of type 2 DM (group 1) participated in this study and twenty subjects who had no diagnosis of type 2 DM were evaluated as a control group (group 2). Blood glucose level of patients was measured then they referred to audiovestibular assessment. Computerized dynamic posturography (CDP) was done in the form of motor control test and functional limitation assessment; Tandem walk. ResultsFindings showed a statistically significant difference between the study group and control group as regards response latency, speed of the forward progression and endpoint sway velocity. A statistically significant correlation was found between response latency and speed of the forward progression with FBS level in the study group. ConclusionsSpeed of the forward progression was less, however response latency and endpoint sway velocity were more in diabetic patients in comparison with normal subjects. Response latency and speed of the forward progression showed a statistically significant correlation with FBS level in diabetic patients.

Characteristics of muscle cramps in patients with polyneuropathy

Muscle cramps are common in the general population and can be disabling for patients, but there is little evidence comprehensively evaluating cramp characteristics in patients with polyneuropathy. This study describes the prevalence and characteristics of muscle cramps in this patient group. Patients over 18 diagnosed with polyneuropathy were invited to join the study. Patients completed nerve conduction studies, the Toronto Clinical Neuropathy score, neuropathy-specific Vickrey’s Quality of Life Assessment and a self-administered questionnaire examining demographics, neuropathy symptoms and cramp characteristics. Two hundred and twenty-five participants were enrolled (28.0% female). Sixty-three percent of patients experienced cramps, occurring on average 6 times per week, lasting 10.5min and scoring 6 out of 10 on a pain scale and described as disabling by 43.6% of patients. No significant difference was found in cramp prevalence according to underlying pathophysiology (p=0.52) or fiber type (p=0.41). Patients with disabling cramps rated their physical (p<0.0001) and mental (p=0.04) quality of life lower than patients without disabling cramps. This study confirms that muscle cramps are common, disabling and associated with reduced quality of life in patients with polyneuropathy. Similar prevalence of cramps across predominant nerve fiber type suggests a role of sensory afferents in cramp generation, although this needs to be confirmed in larger cohorts.

Discriminative and affective touch: sensing and feeling.

The multimodal properties of the human somatosensory system continue to be unravelled. There is mounting evidence that one of these submodalities-touch-has another dimension, providing not only its well-recognized discriminative input to the brain, but also an affective input. It has long been recognized that touch plays an important role in many forms of social communication and a number of theories have been proposed to explain observations and beliefs about the "power of touch." Here, we propose that a class of low-threshold mechanosensitive C fibers that innervate the hairy skin represent the neurobiological substrate for the affective and rewarding properties of touch.

Effect of siRNA Against ß-NGF on Nerve Fibers of a Rat Model With Endometriosis

This study examines whether silencing specific β-nerve growth factor small interfering RNA (β-NGF siRNA) can affect the growth of ectopic endometriotic implants, generalized hyperalgesia, and nerve fiber density in endometriosis. Four specific β-NGF siRNAs were detected by Western blot analysis, and the most efficient specific siRNA was transferred into rats with surgically induced endometriosis through gene transfer. The length × width × height of each ectopic transplant that survived from 2 groups were measured at pre-and postbombardment after 2 weeks. The transplants were collected 2 weeks after bombardment. Warm-water tail flick test was performed before the rats were sacrificed. The specimens were sectioned and stained immunohistochemically with antibodies against the types of nerve fibers to compare the presence of different nerve fibers in the treatment and control groups. The serums and supernatants of the peritoneal washings in the treatment and control groups were collected for enzyme-linked immunosorbent assay (ELISA) analysis. The extra rats were successfully induced with endometriosis and through gene transfer as described above. The spherical volumes of the transplants and tail flick latency post-bombardment after 4, 6, 8, and 10 weeks were measured. The spherical volumes in the treatment group were much smaller than those in the control group, and tail flick latency significantly increased in the treatment group postbombardment after 2 weeks. The ELISA analysis showed that the concentrations of β-NGF in the serums and supernatants of the peritoneal fluid decreased in the treatment group unlike in the control group. Less sympathetic and sensory innervation was observed in the treatment group postbombardment after 2 weeks. The outcomes of the spherical volumes of the transplants and tail flick latency postbombardment after 4, 6, 8, and 10 weeks showed that the sizes of the transplants did not return to their previous size and that the treatment had some effects on generalized hyperalgesia. Specific siRNA-mediated silencing of the β-NGF gene expression after gene transfer suppressed the growth of ectopic endometriotic implants resulted in a significant improvement in generalized hyperalgesia as well as reduced sympathetic and sensory nerve fiber density in the treatment group.

Changes in the innervation of the mouse internal anal sphincter during aging

The innervation of the mouse internal anal sphincter (IAS) has been little studied, and how it changes during aging has not previously been investigated. The aim of this study was therefore to characterize the distribution and density of subtypes of nerve fibers in the IAS and underlying mucosa in 3-, 12- to 13-, 18- and 24- to 25-month-old male C57BL/6 mice. Nerve fibers were immunolabeled with antibodies against protein gene product 9.5 (PGP9.5), neuronal nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), and calretinin (CR). Immunoreactivity in nerve fibers in the circular muscle and mucosa was quantified using Image J software. In young adult (3month) mice, nNOS-immunoreactive (IR) nerve fibers were densely distributed in the circular muscle, but relatively few in the mucosa; VIP-IR nerve fibers were abundant in the circular muscle and common in the mucosa; SP-IR nerve fibers were common in circular muscle and mucosa; CGRP- and CR-IR nerve fibers were dense in mucosa and sparse in circular muscle. The density of PGP9.5 immunoreactivity (IRY) was not significantly reduced with age, but a significant reduction in nNOS-IRY and SP-IRY with age was found in the IAS circular muscle. Neuronal nitric oxide synthase-, VIP-, and SP-IRY in the anal mucosa were significantly reduced with age. CGRP-IRY in both circular muscle and mucosa was increased in 18-month-old animals. The density of immunoreactivity of markers for some types of IAS nerve fibers decreases during aging, which may contribute to age-related ano-rectal dysfunction.

High-resolution measurement of electrically-evoked vagus nerve activity in the anesthetized dog

Objective. Not fully understanding the type of axons activated during vagus nerve stimulation (VNS) is one of several factors that limit the clinical efficacy of VNS therapies. The main goal of this study was to characterize the electrical recruitment of both myelinated and unmyelinated fibers within the cervical vagus nerve. Approach. In anesthetized dogs, recording nerve cuff electrodes were implanted on the vagus nerve following surgical excision of the epineurium. Both the vagal electroneurogram (ENG) and laryngeal muscle activity were recorded in response to stimulation of the right vagus nerve. Main results. Desheathing the nerve significantly increased the signal-to-noise ratio of the ENG by 1.2 to 9.9 dB, depending on the nerve fiber type. Repeated VNS following nerve transection or neuromuscular block (1) enabled the characterization of A-fibers, two sub-types of B-fibers, and unmyelinated C-fibers, (2) confirmed the absence of stimulation-evoked reflex compound nerve action potentials in both the ipsilateral and contralateral vagus nerves, and (3) provided evidence of stimulus spillover into muscle tissue surrounding the stimulating electrode. Significance. Given the anatomical similarities between the canine and human vagus nerves, the results of this study provide a template for better understanding the nerve fiber recruitment patterns associated with VNS therapies.

Enhancement and Distortion in the Temporal Representation of Sounds in the Ventral Cochlear Nucleus of Chinchillas and Cats

A subset of neurons in the cochlear nucleus (CN) of the auditory brainstem has the ability to enhance the auditory nerve's temporal representation of stimulating sounds. These neurons reside in the ventral region of the CN (VCN) and are usually known as highly synchronized, or high-sync, neurons. Most published reports about the existence and properties of high-sync neurons are based on recordings performed on a VCN output tract—not the VCN itself—of cats. In other species, comprehensive studies detailing the properties of high-sync neurons, or even acknowledging their existence, are missing.Examination of the responses of a population of VCN neurons in chinchillas revealed that a subset of those neurons have temporal properties similar to high-sync neurons in the cat. Phase locking and entrainment—the ability of a neuron to fire action potentials at a certain stimulus phase and at almost every stimulus period, respectively—have similar maximum values in cats and chinchillas. Ranges of characteristic frequencies for high-sync neurons in chinchillas and cats extend up to 600 and 1000 Hz, respectively. Enhancement of temporal processing relative to auditory nerve fibers (ANFs), which has been shown previously in cats using tonal and white-noise stimuli, is also demonstrated here in the responses of VCN neurons to synthetic and spoken vowel sounds.Along with the large amount of phase locking displayed by some VCN neurons there occurs a deterioration in the spectral representation of the stimuli (tones or vowels). High-sync neurons exhibit a greater distortion in their responses to tones or vowels than do other types of VCN neurons and auditory nerve fibers.Standard deviations of first-spike latency measured in responses of high-sync neurons are lower than similar values measured in ANFs' responses. This might indicate a role of high-sync neurons in other tasks beyond sound localization.

Будова та кровопостачання L2-S2 дорзальних корінців спинного мозку щурів різного віку

The paper presents information of hystometryc and electron microscopic research of nerve fibres of spinal cord dorsal roots and their blood circulation system of rats in the postnatal period of ontogenesis. The basic types of nerve fibres are revealed and characterized. Their composition which reflects the close morphological mutually causal structure of nerves and ways of blood microcirculatory is shown. It can determine the character of age-specific processes in the dorsal roots.

Substance P and norepinephrine modulate murine chondrocyte proliferation and apoptosis

Substance P (SP) and norepinephrine (NE) containing sensory and sympathetic nerve fibers innervate bone and fracture callus. They are involved in controlling vascularization and matrix differentiation during skeletal growth. Both types of nerve fibers are known to modulate growth and metabolic activity of osteoblasts and osteoclasts. The aim of this study was to understand the roles of SP and NE in chondrocyte metabolism and their impact on chondrocyte proliferation, apoptosis, and cell adhesion. Primary costal chondrocytes were isolated from newborn mice. Micromass and monolayer cell culture regimens were used to analyze the effects of SP and NE on matrix formation, as determined by quantitative polymerase chain reaction and immunohistochemistry. The effects of SP and NE on proliferation, adhesion, and apoptosis of chondrocytes were determined by enzyme-linked immunosorbent assay, bromodeoxyuridine, TUNEL, and morphometric analyses. SP, neurokinin type 1 (NK-1) receptor, α-adrenergic receptor (α-AR), and β-AR were abundantly expressed in primary costal chondrocytes. Stimulation with SP or NE did not affect extracellular matrix formation with respect to types I, II, and IX collagen and aggrecan in micromass pellets. SP dose-dependently increased the rate of proliferation of chondrocytes via the NK-1 receptor, whereas NE decreased the apoptosis rate of chondrocytes by stimulating β-AR. Both neurotransmitters induced the formation of focal adhesion contacts. Transmitters of sympathetic and sensory nerve fibers modulate the metabolic activity of chondrocytes. Endogenous SP, NK-1 receptor, and adrenoceptor expression in chondrocytes implicates as-yet-unknown, presumably trophic, functions of neurotransmitter for skeletal growth and might be of interest for use in cartilage regenerative medicine.

Tissue Preparation and Immunostaining of Mouse Sensory Nerve Fibers Innervating Skin and Limb Bones

Detection and primary processing of physical, chemical and thermal sensory stimuli by peripheral sensory nerve fibers is key to sensory perception in animals and humans. These peripheral sensory nerve fibers express a plethora of receptors and ion channel proteins which detect and initiate specific sensory stimuli. Methods are available to characterize the electrical properties of peripheral sensory nerve fibers innervating the skin, which can also be utilized to identify the functional expression of specific ion channel proteins in these fibers. However, similar electrophysiological methods are not available (and are also difficult to develop) for the detection of the functional expression of receptors and ion channel proteins in peripheral sensory nerve fibers innervating other visceral organs, including the most challenging tissues such as bone. Moreover, such electrophysiological methods cannot be utilized to determine the expression of non-excitable proteins in peripheral sensory nerve fibers. Therefore, immunostaining of peripheral/visceral tissue samples for sensory nerve fivers provides the best possible way to determine the expression of specific proteins of interest in these nerve fibers. So far, most of the protein expression studies in sensory neurons have utilized immunostaining procedures in sensory ganglia, where the information is limited to the expression of specific proteins in the cell body of specific types or subsets of sensory neurons. Here we report detailed methods/protocols for the preparation of peripheral/visceral tissue samples for immunostaining of peripheral sensory nerve fibers. We specifically detail methods for the preparation of skin or plantar punch biopsy and bone (femur) sections from mice for immunostaining of peripheral sensory nerve fibers. These methods are not only key to the qualitative determination of protein expression in peripheral sensory neurons, but also provide a quantitative assay method for determining changes in protein expression levels in specific types or subsets of sensory fibers, as well as for determining the morphological and/or anatomical changes in the number and density of sensory fibers during various pathological states. Further, these methods are not confined to the staining of only sensory nerve fibers, but can also be used for staining any types of nerve fibers in the skin, bones and other visceral tissue.

Improvement of Diameter Selectivity in Nerve Recruitment Using Multi-cuff Electrodes

Since the conventional methodof electrical stimulation deliveredusing an extracellular electrode has poor selectivity in terms of nerve fiber type, it is difficult to avoid recruiting antitarget nerve fibers. For example, recruitment of motor fibers by electrical stimulation frequently causes unpleasant symptoms such as pain sensation andnumbness. Many electrical stimulation method s have been proposedto achieve nerve type- specific recruitment based on diameter dependence ; however, experimental evaluations have suggested insufficient selectivity of these methods. In this study, we evaluated diameter-selective recruitment using triple- cuff electrodes, which are composed of a single cathodic cuff electrode sandwiched between two anodic cuff electrodes with various anode-to-cathode distances, De . Using numerical simulations, we determined the stimulation-response characteristics as functions of stimulus intensity (IC) andfiber d iameter D (1-20 μmϕ), when De values were set at infinite and2-mm distances. We observedthat thinner axons were recruitedas IC in- creased and that the thresholds for cathodic excitation and anodal block were dependent on De. The dependence of threshold intensities for cathodic excitation and anodal block on various axon diameters at each De was analyzed . The results confirmedthat thin axons hadhigher threshold s andthat thresholdintensities were nonmonotonically dependent on De . When De was set to infinite distance (corresponding to a single-cuff electrode) and IC was relatively low, only thick axons (≥10 μmϕ ,e . g., Aα fiber group) were selectively recruited. By decreasing De to about 2 mm andincreasing the stimulus intensity, thicker axons were suppressedby anodal block ; in contrast, thinner axons (≤10 μmϕ) became selectively recruited. It was possible to recruit either moderately thick (5-9 μmϕ ,e . g., Aβ fiber group) or thin (2-4 μmϕ ,e . g., Aδ fiber group) axons by scrutinizing the De and IC dependence of nerve recruitment. Axon response was robust against radial position in the nerve bundle. These results suggest that electrical stimulation using a triple-cuff electrode properly adjusted for both stimulus intensity and distance between the anodic and cathodic electrodes has the potential for nerve-specific recruitment within a nerve bundle.

The dimensions and characteristics of the subepidermal nerve plexus in human skin – Terminal Schwann cells constitute a substantial cell population within the superficial dermis

The skin constitutes the largest sensorial organ. Its nervous system consists of different types of afferent nerve fibers which spread out immediately beneath the skin surface to sense temperature, touch and pain. Our aim was to investigate the dimension and topographic relationship of the different nerve fibers of the subepidermal nerve plexus in human hairy skin and to analyze numbers and marker expression of terminal Schwann cells. Nerve fibers and Schwann cells were investigated on dermal sheet preparations and thick sections of skin from various body regions of 10 individuals. The dimension of subepidermal nerve fibers varied between different body sites with highest values in chest skin (100 ± 18 mm/mm(2)) and lowest in posterior forearm skin (53 ± 10 mm/mm(2)). The majority of fibers (85.79%) were unmyelinated, thus representing C-fibers, of which 7.84% were peptidergic. Neurofilament-positive fibers (A-fibers) accounted for 14.21% and fibers positive for both neurofilament and myelin (Aβ-fibers) for only 0.18%. The number of Schwann cells varied in accordance with nerve fiber length from 453 ± 108 on chest skin to 184 ± 58/mm(2) in skin of the posterior forearm. Terminal Schwann cells showed a marker profile comparable to Schwann cells in peripheral nerves with the notable exception of expression of NGFr, NCAM, L1CAM and CD146 on myelinating Schwann cells in the dermis but not in peripheral nerves. Our data show that terminal Schwann cells constitute a substantial cell population within the papillary dermis and that both nerve fiber length and Schwann cell numbers vary considerably between different body sites.

From comfort to pain: Neural basis of ocular surface sensations

AbstractThe exposed surface of the eye is richly innervated by sensory nerve fibers originated at trigeminal ganglion neurons. They reach the cornea and bulbar conjunctiva as thin myelinated or unmyelinated nerve fibers lacking of morphological terminal specialization. However, electrophysiological studies have shown that sensory neurons innervating the eye are functionally heterogeneous. Based upon their response to specific stimuli, different functional types of sensory nerve fibers have been identified in the cornea and bulbar conjunctiva. Mechanonociceptor fibers (~20% of the total) react only to mechanical forces; polymodal nociceptor fibers (~70%) respond to mechanical forces but also to heat, exogenous chemical irritants and endogenous inflammatory mediators. Cold‐sensitive fibers (~10‐15%) display an ongoing impulse activity at basal corneal temperatures and increase markedly their firing frequency with moderate cooling. Differences in transduction capacity among ocular sensory fibers are attributable to the variable expression of different types of transduction channels (members of the TRP superfamily, ASICs, 2P domain K channels..) HCN channels and of voltage‐dependent Na+ K+ and Ca2+ channels. Under pathological conditions (inflammation, surgical injury, dryness of the ocular surface) activity of ocular sensory nerve fibers changes markedly as the result of short‐term changes in ion channel expression secondary to local release of inflammatory agents and growth factors, and of long‐lasting modifications in gene expression. This leads to the development of spontaneous activity and of abnormal responsiveness to natural stimuli. Each of the functional types of corneal sensory fibers can be stimulated selectively in humans, using an instrument (the Belmonte esthesiometer) that delivers gas pulses of variable flow at neutral temperature (mechanical stimuli), CO2 concentrations (acidic stimuli) and cooled or warmed air at subthreshold flow levels (cold and heat stimuli) onto the ocular surface. Stimulation of the different functional populations of nerve fibers of the ocular surface evokes a specific quality of sensation that includes a variable component of unpleasantness. The relationship between activation of the different classes of ocular surface sensory fibers under normal and pathological conditions and the quality of the experienced sensation is now being elucidated. In addition to their role in the production of conscious innocuous and noxious sensations referred to the eye surface, sensory fibers appear to play a role in the maintenance of the ocular surface homeostasis, including basal and reflex modulation of tearing and trophic maintenance of corneal and conjunctival tissues. Supported by grants BFU2005‐08741 and CONSOLIDER‐INGENIO 2010 CSD2007‐00023 from the Government of Spain.

The reinnervation and revascularization of wounds is temporarily altered after treatment with interleukin 10

Denervated wounds fail to heal normally, and hypertrophic scars are abnormally innervated. Wounds can be manipulated with cytokines to reduce subsequent scarring. Wounds treated with the antiscarring cytokine interleukin 10 (IL10) were investigated to assess if the treatment alterered patterns of reinnervation and revascularization as the wounds matured into scars. Thirty CD1 mice underwent intradermal injection of 100 μL phosphate-buffered saline (PBS) containing 125 ng IL10 or placebo at the margins of 1 cm(2) full thickness dorsal skin excisions at the time of wounding and at 24 hours after wounding. Wounds were not dressed. Six IL10-treated and six control were harvested days 7, 14, 21, 42 and 84 postoperatively. Sections underwent histological scar assessment along with immunohistochemical staining for protein gene product 9.5 (PGP9.5), a pan-neuronal marker, and the sensory neuropeptides calcitonin gene related peptide (CGRP) and substance P (SP). The endothelial marker von Willebrand factor (VWF) was used to allow co-localization and quantification of blood vessels. Quantitative analysis was performed on the periphery and center of wounds. Wounds treated with IL10 healed with dermal collagen organized into a pattern more closely resembling normal skin than control wounds. IL10 changed the pattern of CGRP reinnervation during the healing process, but at 84 days, the density levels of all nerve fiber types were similar to controls. Wounds treated with IL10 were more vascular than untreated wounds during healing, but by 84 days, VWF density was that of unwounded skin.

Guidelines and recommendations for assessment of somatosensory function in oro-facial pain conditions - a taskforce report

The goals of an international taskforce on somatosensory testing established by the Special Interest Group of Oro-facial Pain (SIG-OFP) under the International Association for the Study of Pain (IASP) were to (i) review the literature concerning assessment of somatosensory function in the oro-facial region in terms of techniques and test performance, (ii) provide guidelines for comprehensive and screening examination procedures, and (iii) give recommendations for future development of somatosensory testing specifically in the oro-facial region. Numerous qualitative and quantitative psychophysical techniques have been proposed and used in the description of oro-facial somatosensory function. The selection of technique includes time considerations because the most reliable and accurate methods require multiple repetitions of stimuli. Multiple-stimulus modalities (mechanical, thermal, electrical, chemical) have been applied to study oro-facial somatosensory function. A battery of different test stimuli is needed to obtain comprehensive information about the functional integrity of the various types of afferent nerve fibres. Based on the available literature, the German Neuropathic Pain Network test battery appears suitable for the study of somatosensory function within the oro-facial area as it is based on a wide variety of both qualitative and quantitative assessments of all cutaneous somatosensory modalities. Furthermore, these protocols have been thoroughly described and tested on multiple sites including the facial skin and intra-oral mucosa. Standardisation of both comprehensive and screening examination techniques is likely to improve the diagnostic accuracy and facilitate the understanding of neural mechanisms and somatosensory changes in different oro-facial pain conditions and may help to guide management.

A comparison of neurosensory alteration and recovery pattern among different types of orthognathic surgeries using the current perception threshold

The objective of this study was to compare postsurgical neurosensory alteration and recovery patterns among different nerve fiber types and orthognathic surgeries by measuring current perception thresholds (CPT). CPTs of 186 patients who underwent various orthognathic surgeries (Le Fort I or II, bilateral sagittal split [BSSRO] or intraoral vertico-sagittal [IVSRO] ramus osteotomy with or without genioplasty) were measured at 2000, 250, and 5 Hz, assessing 3 different nerve fiber types before surgery and at 3, 6, and 12 months after surgery. CPTs were highest at 3 months postsurgery and gradually returned to presurgical levels until 12 months postsurgery in most cases. CPT at 2000 Hz showed the largest amount of increase. Le Fort I and IVSRO caused less neurosensory alteration compared with Le Fort II and BSSRO, respectively. Our data provide nerve recovery patterns following various orthognathic surgeries that may be applied to evaluating the patient's severity and recovery of nerve damage.