Pad Skin Research Articles

Evaluating the effects of bedding materials and elevated platforms on contact dermatitis and plumage cleanliness of commercial broilers and on litter condition in broiler houses

ABSTRACT1. Experiment 1, comparing wood shavings and ground straw bedding with peat, was performed on 7 broiler farms over two consecutive batches during the winter season. Experiment 2, assessing the effect of elevated (30 cm) platforms, was conducted in three farms replicated with 6 consecutive batches.2. Footpad lesions were inspected at slaughter following the Welfare Quality® (WQ) assessment and official programme. Hock lesions, plumage cleanliness and litter condition were assessed using the WQ assessment. Litter height, pH, moisture and ammonia were determined.3. Footpad condition on wood shavings appeared to be worse compared with peat using both methods of assessment and was accompanied by inferior hock skin health. WQ assessment resulted in poorer footpad and hock skin condition on ground straw compared with peat. Farms differed in footpad and hock skin condition. Footpad and hock lesions were not affected by platform treatment. Peat appeared more friable than ground straw. The initial pH of wood shavings was higher and moisture was lower than in peat, but at the end of production period there were no differences. Ground straw exhibited higher initial and lower end pH, and was drier in the beginning than peat. Litter condition and quality were not affected by platform treatment.4. This study provides new knowledge about the applicability of peat as broiler bedding and shows no negative effects of elevated platforms on litter condition or the occurrence of contact dermatitis in commercial environments. The results suggest a complicated relationship between litter condition, moisture and contact dermatitis. Furthermore, it is concluded that the farmer’s ability to manage litter conditions is important, regardless of the chosen litter material. Peat bedding was beneficial for footpad and hock skin health compared with wood shavings and ground straw.

Comparison of the Effect of Skin Preparation Pads on Transepidermal Water Loss in Ex Vivo Human Skin.

IntroductionPre-treatment of the skin to remove scales and crusts prior to photodynamic therapy (PDT) is essential to enhance the uptake of topically applied methyl aminolevulinate (MAL) and to improve treatment efficacy. This study compared the effect of two different skin preparation pads on skin integrity in ex vivo human skin.MethodsEx vivo human skin samples from three donors were pre-treated in triplicates with PREPSTER™ (PR) skin preparation pad (6, 8, and 10 passages) or Ambu Unilect™ (A-UN) skin preparation pad (6, 8, and 10 passages). In addition, skin samples were pre-treated with tape strippings (10 adhesive tape strips) as a reference method for comparison. Transepidermal water loss (TEWL) was measured on intact skin and following skin barrier impairment using skin preparation pads and tape stripping. Histological analysis was performed to verify the impairment of the stratum corneum (SC) barrier function in samples from intact skin (control), 10 tape strippings (reference method), 10 passages of PR, and 10 passages of A-UN.ResultsTEWL increased with the increasing number of passages of skin preparation pads, with 2.4- and 3.3-fold increases following 10 passages of A-UN and PR, respectively, versus a 2.2-fold increase with 10 tape strippings (reference). Histological analysis showed only partial removal of the SC, with no damage observed on the epidermis, regardless of the procedure used.ConclusionPre-treatment of skin using PR and A-UN skin preparation pads markedly increases TEWL, indicating slight impairment of the SC barrier function. Comparison of both skin preparation pads showed that PR pad consistently induced significantly higher TEWL than A-UN pad (p < 0.05), regardless of the number of passages. Both skin preparation pads are thought to increase the uptake of MAL and can therefore be used for the preparation of skin prior to PDT.FundingNestlé Skin Health – Galderma R&D.

Botulinum neurotoxin A promotes functional recovery after peripheral nerve injury by increasing regeneration of myelinated fibers

The injection of safe doses of botulinum neurotoxin A (BoNT/A) have been reported to be useful for the treatment of neuropathic pain, but it is still unknown how functional recovery is induced after peripheral nerve injury. We evaluated the effects of intranerve application of BoNT/A, on regeneration and sensorimotor functional recovery in partial and complete peripheral nerve injuries in the mouse. After sciatic nerve crush (SNC) and intranerve delivery of BoNT/A (15pg), axonal regeneration was measured by nerve pinch test at different days. Regeneration of myelinated and unmyelinated fibers was assessed by immunohistochemical double labeling for NF200/GAP43 and CGRP/GAP43. S100 was used as Schwann cells marker. Medial footpad skin reinnervation was assessed by PGP staining. Motor functions were assessed by means of nerve conduction tests. In other mice groups, nerve conduction tests were performed also after chronic constriction injury (CCI) of the sciatic nerve and intraplantar injection of BoNT/A (15pg). In SNC mice, BoNT/A increased the rate of axonal regeneration. The advantage of regrowing myelinated axons after BoNT/A injection was evidenced by longer NF200+ nerve profiles and confirmed by nerve histology. We observed also a higher expression of S100 in the distal portion of BoNT/A-injected regenerated nerves. In CCI mice, BoNT/A induced an increase in reinnervation of gastrocnemius and plantar muscles. These results show that a low dose of BoNT/A, insufficient to produce muscular dysfunction, conversely speeds up sensorimotor recovery by stimulating myelinated axonal regeneration, and points out its application as a multipotent treatment for peripheral neuropathies.

FSOCA-induced switchable footpad skin optical clearing window for blood flow and cell imaging in vivo.

The mouse footpad for its feature of hairlessness provides an available window for imaging vascular and cellular structure and function in vivo. Unfortunately, the strong scattering of its skin limits the penetration of light and reduces the imaging contrast and depth. Herein, an innovative footpad skin optical clearing agent (FSOCA) was developed to make the footpad skin transparent quickly by topical application. The results demonstrate that FSOCA treatment not only allowed the cutaneous blood vessels and blood flow distribution to be monitored by laser speckle contrast imaging technique with higher contrast, but also permitted the fluorescent cells to be imaged by laser scanning confocal microscopy with higher fluorescence signal intensity and larger imaging depth. In addition, the physiological saline-treatment could make the footpad skin recover to the initial turbid status, and reclearing would not induce any adverse effects on the distributions and morphologies of blood vessels and cells, which demonstrated a safe and switchable window for biomedical imaging. This switchable footpad skin optical clearing window will be significant for studying blood flow dynamics and cellular immune function in vivo in some vascular and immunological diseases. Picture: Repeated cell imaging in vivo before (a) and after (b) FSOCA treatment. (c) Merged images of 4 h (cyan border) or 72 h (magenta border) over 0 h. (d) Zoom of ROI in 4 h (yellow rectangle) or 72 h (red rectangle).

The Effect Of Drink Temperature On Sweating Response And Performance During Exercise In The Heat

Drink temperature disproportionately influences sweating rate and volume during low intensity exercise in temperate conditions that permit full sweat evaporation. Specifically, cold drinks may reduce sweat production and hot drinks are thought to increase it by stimulation of a gut thermoreceptor. Consequently, cold drinks may have a negative influence on thermoregulatory responses during exercise in the heat. PURPOSE: The effect of drink temperature has yet to be examined on the sweat response, thermoregulation and performance in hot, dry conditions using an ecologically valid protocol with measurement of regional sweating responses. METHODS: Ten trained cyclists completed three trials prior to and during which they ingested 3.2 mL.kg-1 of a COLD (5.3 ± 1.7 °C) or HOT drink (49.0 ± 1.9 °C), which was contrasted to a no drink CONTROL. They cycled in hot, dry conditions (34.5 ± 0.6 °C & 22 ± 1% RH) for 60-minutes at 55% of pre-determined maximal power output (Pmax) and then completed a test to exhaustion at 80% Pmax. Thermal (rectal temperature Trec, 8-site skin temperature Tmsk) and local sweat rate responses (absorbent sweat pad & galvanic skin conductance GSC) were recorded. TTE duration indicated the performance effect. Comparisons were made using ANOVA. Data are displayed as mean [SD]. RESULTS: Participant’s TTE performance was significantly worse in the CONTROL (170 [132] s) condition (p<0.05) than the COLD (371 [272] s) and HOT drink (367 [301] s) conditions which did not differ. Throughout the fixed intensity exercise period, local sweat responses at the bicep and upper back were not different (p>0.05) between any of the test conditions (e.g. grand mean [SD] Bicep GSC CONTROL 15.2 [8.0] μS, HOT 17.3 [8.0] μS & COLD 14.0 [6.0] μS). Temperature responses were higher (p<0.05) in the CONTROL than both drink conditions at the core (Trec, CONTROL 38.3 [0.5] °C, COLD 38.0 [0.5] °C, HOT 38.1 [0.5] °C) but not the skin (CONTROL 34.5 [0.2] °C, COLD 34.5 [0.3] °C, HOT 34.6 [0.3] °C). CONCLUSION: Drink temperature did not influence performance, temperature responses or regional sweat responses during high-intensity exercise in hot, dry conditions. Consumption of fluid, irrespective of its temperature, provided a benefit to exercise performance in the heat in contrast to not drinking. Supported by European Hydration Institute Grant.

Assessment of health and welfare of Austrian laying hens at slaughter demonstrates influence of husbandry system and season

ABSTRACT1. Selected health and welfare variables of laying hens from 79 flocks kept in alternative husbandry systems were assessed at the end of lay.2. Investigations were carried out on 100 hens per flock at the slaughter line and recorded as part of a novel scoring system. In addition, post-mortem investigations as well as parasitological examinations were conducted on 10 birds from each flock.3. Birds with access to free range had better plumage than birds kept in barn systems. Housing in aviaries was associated with a higher prevalence of foot pad lesions and keel bone deformations. In addition, poorer plumage, more and worse skin and foot pad lesions were documented in hens slaughtered during the winter months.4. Oophoritis and/or salpingitis were the most prevalent pathomorphological changes observed. Intestinal parasites, especially Heterakis gallinarum and Ascaridia galli, were frequent. Hens kept indoors had fewer nematoda and cestoda than those from conventional and organic free range.5. The slaughterhouse protocol allowed direct comparison of variables between flocks and specific problems to be identified in particular flocks. The results could be used to initiate detailed investigations into problematic issues on selected farms.

Oxytocin alleviates orofacial mechanical hypersensitivity associated with infraorbital nerve injury through vasopressin-1A receptors of the rat trigeminal ganglia.

Oxytocin (OXT) is a neuropeptide hormone synthesized and secreted by hypothalamic neurons and has been reported to play a significant role in pain modulation. However, the mechanisms underlying OXT's antinociceptive effect on neuropathic pain are not fully understood. In this study, we examined the peripheral effect of OXT on mechanical hypersensitivity induced by partial ligation of the infraorbital nerve (PNL) in rats. Mechanical hypersensitivity in the whisker pad skin after PNL was attenuated by the direct administration of OXT into the trigeminal ganglion (TG). The proportion of vasopressin-1A receptor (V1A-R)-immunoreactive, but not OXT-receptor-immunoreactive, neurons significantly increased among TG neurons innervating the whisker pad skin after PNL. In a patch-clamp recording from TG neurons isolated from PNL rats, the resting membrane potential of OXT-treated neurons was significantly decreased, and the current thresholds of OXT-treated neurons for spike generation (rheobases) were significantly greater than those of vehicle-treated neurons. In addition, OXT increased voltage-gated K channel currents in PNL animals. Furthermore, intra-TG administration of a selective V1A-R antagonist reversed the OXT-induced alleviation of mechanical hypersensitivity, and coapplication of the antagonist opposed OXT's effects on the resting membrane potential, rheobase, and K current. These findings suggest that OXT is effective at suppressing TG neuronal hyperexcitability after nerve injury, likely by modulation of voltage-gated K channels through V1A-R. This signaling mechanism represents a potential therapeutic target for the treatment of orofacial neuropathic pain.

Effect of the Direction of Finger Pad Skin Stretch on Reproduction of Tracing Sensation

Effect of the Direction of Finger Pad Skin Stretch on Reproduction of Tracing Sensation

Botulinum neurotoxin type A alleviates mechanical hypersensitivity associated with infraorbital nerve constriction injury in rats

We investigated the effect of botulinum neurotoxin type A (BoNT-A) on mechanical allodynia and hyperalgesia associated with infraorbital nerve constriction (ION-CCI) in rats. ION-CCI rats received a subcutaneous BoNT-A injection into the whisker pad area on day 7 postoperatively and underwent pain assessment on days 14 and 21 postoperatively. Rats were assigned to one of four treatment groups (n=5 each): ION-CCI+BoNT-A 20pg (low-dose group), ION-CCI+BoNT-A 200pg (high-dose group), ION-CCI+saline, and Sham. Mechanical allodynia and hyperalgesia were evaluated preoperatively (baseline) and on days 7, 14, and 21 postoperatively. After noxious mechanical stimulation of whisker pad skin, the number and distribution pattern of the phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive (IR) neurons were analyzed in the trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2). On day 21, nocifensive behavior was attenuated by high-dose but not low-dose BoNT-A administration. In addition, after noxious mechanical stimulation of whisker pad skin, the numbers of pERK-IR cells in the superficial laminae of Vc and C1-C2 were significantly lower in the high-dose BoNT-A group than in the ION-CCI+saline group. The present findings suggest that, by suppressing Vc neuronal activity, high-dose intradermal injection of BoNT-A at the site of ION innervation alleviates mechanical facial allodynia and hyperalgesia associated with ION-CCI.

Maternal Separation Induces Orofacial Mechanical Allodynia in Adulthood

It is well known that exposure to maternal separation (MS) in early life causes plastic changes in the nervous system in adulthood, occasionally resulting in ubiquitous chronic pain. However, the pathogenic mechanisms of pain hypersensitivity remain unclear. Here, the authors examined the involvement of corticosterone in orofacial mechanical hypersensitivity induced by MS. To establish a rat model of MS, pups were placed in isolated cages 180 min/d and kept in a temperature-controlled environment at 22 ± 2 °C for 14 d. Mechanical allodynia in the whisker pad skin in adulthood was induced by MS and was significantly suppressed by successive postnatal subcutaneous administration of the glucocorticoid receptor antagonist mifepristone. Corticosterone levels were increased in the serum of MS rats, and successive postnatal administration of subcutaneous corticosterone to naive rats induced mechanical allodynia in the whisker pad skin. The number of P2X3 receptor-immunoreactive (P2X3R-IR) trigeminal ganglion (TG) neurons innervating the whisker pad skin was significantly increased in MS rats and decreased following subcutaneous administration of mifepristone. The number of P2X3R-IR TG neurons innervating the whisker pad skin was also significantly increased following successive postnatal administration of subcutaneous corticosterone in naive rats. Moreover, the mechanical allodynia was suppressed 30 min after administration of the P2X3R antagonist A317491 to the whisker pad skin in MS rats. These findings suggest that the increase in P2X3R-IR TG neurons innervating the whisker pad skin via enhanced neonatal corticosterone signaling by MS plays an important role in orofacial mechanical allodynia in adulthood.

Tracking Epidermal Nerve Fiber Changes in Asian Macaques: Tools and Techniques for Quantitative Assessment.

Quantitative assessment of epidermal nerve fibers (ENFs) has become a widely used clinical tool for the diagnosis of small fiber neuropathies such as diabetic neuropathy and human immunodeficiency virus-associated sensory neuropathy (HIV-SN). To model and investigate the pathogenesis of HIV-SN using simian immunodeficiency virus (SIV)-infected Asian macaques, we adapted the skin biopsy and immunostaining techniques currently employed in human patients and then developed two unbiased image analysis techniques for quantifying ENF in macaque footpad skin. This report provides detailed descriptions of these tools and techniques for ENF assessment in macaques and outlines important experimental considerations that we have identified in the course of our long-term studies. Although initially developed for studies of HIV-SN in the SIV-infected macaque model, these methods could be readily translated to a range of studies involving peripheral nerve degeneration and neurotoxicity in nonhuman primates as well as preclinical investigations of agents aimed at neuroprotection and regeneration.

Oxidative stress and dysfunctional NRF2 underlie pachyonychia congenita phenotypes.

Palmoplantar keratoderma (PPK) are debilitating lesions that arise in individuals with pachyonychia congenita (PC) and feature upregulation of danger-associated molecular patterns and skin barrier regulators. The defining features of PC-associated PPK are reproduced in mice null for keratin 16 (Krt16), which is commonly mutated in PC patients. Here, we have shown that PPK onset is preceded by oxidative stress in footpad skin of Krt16-/- mice and correlates with an inability of keratinocytes to sustain nuclear factor erythroid-derived 2 related factor 2-dependent (NRF2-dependent) synthesis of the cellular antioxidant glutathione (GSH). Additionally, examination of plantar skin biopsies from individuals with PC confirmed the presence of high levels of hypophosphorylated NRF2 in lesional tissue. In Krt16-/- mice, genetic ablation of Nrf2 worsened spontaneous skin lesions and accelerated PPK development in footpad skin. Hypoactivity of NRF2 in Krt16-/- footpad skin correlated with decreased levels or activity of upstream NRF2 activators, including PKCδ, receptor for activated C kinase 1 (RACK1), and p21. Topical application of the NRF2 activator sulforaphane to the footpad of Krt16-/- mice prevented the development of PPK and normalized redox balance via regeneration of GSH from existing cellular pools. Together, these findings point to oxidative stress and dysfunctional NRF2 as contributors to PPK pathogenesis, identify K16 as a regulator of NRF2 activation, and suggest that pharmacological activation of NRF2 should be further explored for PC treatment.

Assessment of exposure to pesticides during mixing/loading and spraying of tomatoes in the open field

ABSTRACTSome evidence of exposure-response of metolachlor and pendimethalin for lung cancer and an association of metribuzin with risk of glioma have been reported. The primary objectives in this study were to evaluate exposure and occupational risk during mixing/loading of pesticides and during their application to tomatoes cultivated in open fields.Sixteen farmers were sampled. Respiratory exposure was estimated by personal air sampling using fiberglass filters in a IOM device. Dermal exposure was assessed using skin pads and hand washing. Absorbed doses were estimated assuming 100% lung retention, and 50% or 10% skin absorption for metribuzin, and pendimethalin and metolachlor, respectively. The three pesticides were quantified by gas chromatography tandem mass spectrometry in all matrices. Metolachlor was used as a tracer of contamination of clothes and tractors unrelated to the exposure monitored.Respiratory exposure to metribuzin, used in granular form, was on average more than one order of magnitude higher than exposure to pendimethalin, used in the form of microencapsulated liquid. The actual doses were 0.067–8.08 µg/kg bw, 0.420–12.6 µg/kg bw, and 0.003–0.877 µg/kg bw for pendimethalin, metribuzin, and metolachlor, respectively. Dermal exposure was about 88% of the actual dose for metribuzin and more than 95%, for pendimethalin and metolachlor. For risk assessment, the total absorbed doses (sum of respiratory and skin absorbed doses) were compared with the AOEL for each compound.The actual and absorbed doses of the three pesticides were always lower than the acceptable operator exposure level (AOEL), which are reported to be 234 µg/kg bw, 20 µg/kg bw, and 150 µg/kg bw for pendimethalin, metribuzin, and metolachlor, respectively. In any case, personal protective equipment and spraying devices should be chosen with care to minimize exposure.

Effects of incubation temperatures and trace mineral sources on chicken live performance and footpad skin development

One experiment was conducted to evaluate the effects of two incubation temperature profiles (TEM) and two trace mineral (TM) sources with their inclusion levels on performance and footpad skin development of Ross 708 chickens. A total of 1,000 eggs from 29-wk-old breeders were incubated following two TEM profiles: a standard (S) eggshell temperature (37.8±0.2°C) for 21 d of incubation and an early-low late-high (LH) TEM. The second profile had low (37.2±0.2°C) temperature for the first 3 d, and S until the last 3 d when eggshell temperature was 39.2±0.2°C. At hatch, 15 male and 15 female chicks from each TEM were selected, and footpads sampled. Additionally, 168 males per TEM were placed in 24 battery cages with 7 chickens each. The 48 cages were assigned to two TM dietary treatments: one with inorganic (ITM) sources of Zn (120 ppm), Cu (10 ppm), and Mn (120 ppm) and the other with chelated (CTM) mineral sources using lower inclusion levels of Zn (32 ppm), Cu (8 ppm), and Mn (32 ppm). At 7 and 21 d, BW gain and feed conversion ratio (FCR) were obtained and chicks sampled for footpads. Histological analysis assessed thickness and area ofstratus corneum(SC), epidermis, and dermis. Data were analyzed as a completely randomized block design in a 2×2 factorial arrangement of treatments with TEM and sex as main factors for hatch data and TEM and TM diets for 7 and 21 d data. The LH chicks were heavier than S chicks at hatch, but had more residual yolk. However, S TEM male chickens were heavier at 7 and 21 d. The S TEM had better FCR than LH TEM.Papillaedermis parameters at hatch were higher in the S TEM. At 7 d, SC height and area were increased by the S TEM. At 21 d CTM increased dermis height and area. In conclusion, TEM affected footpad skin development and broiler performance. Replacing ITM with reduced levels of CTM increased dermis development without affecting live performance or other skin layers.

Identification of Biomarkers for Footpad Dermatitis Development and Wound Healing.

Footpad dermatitis (FPD) is a type of skin inflammation that causes necrotic lesions on the plantar surface of the footpads in commercial poultry, with significant animal welfare, and economic implications. To identify biomarkers for FPD development and wound healing, a battery cage trial was conducted in which a paper sheet was put on the bottom of cages to hold feces to induce FPD of broilers. Day-of-hatch Ross 308 male broiler chicks were fed a corn–soybean meal diet and assigned to 3 treatments with 8 cages per treatment and 11 birds per cage. Cages without paper sheets were used as a negative control (NEG). Cages with paper sheets during the entire growth period (d 0–30) were used as a positive control (POS) to continually induce FPD. Cages with paper sheets during d 0–13 and without paper sheets during d 14–30 were used to examine the dynamic of FPD development and lesion wound healing (LWH). Footpad lesions were scored to grade (G) 1–5 with no lesion in G1 and most severe lesion in G5. Covering with paper sheets in POS and LWH induced 99% incidence of G3 footpads on d 13. Removing paper sheets from LWH healed footpad lesions by d 30. One representative bird, with lesions most close to pen average lesion score, was chosen to collect footpad skin samples for biomarker analysis. Total collagen protein and mRNA levels of tenascin X (TNX), type I α1 collagen (COL1A1), type III α1 collagen (COL3A1), tissue inhibitor of metalloproteinase 3 (TIMP3), and integrin α1 (ITGA1) mRNA levels were decreased (P < 0.05), while mRNA levels of tenascin C (TNC), tumor necrosis factor (TNF) α, Toll-like receptor (TLR) 4 and vascular endothelial growth factor (VEGF), IL-1β, and the ratio of MMP2 to all TIMP were increased (P < 0.03) in G3 footpads in POS and LWH compared to G1 footpads in NEG on d 14. These parameters continued to worsen with development of more severe lesions in POS. After paper sheets were removed (i.e., LWH), levels of these parameters gradually or rapidly returned to levels measured in NEG. Regression analysis indicated significant quadratic changes of these parameters to footpad lesion scores. In summary, these biomarkers were interrelated with dynamic changes of footpad lesion scores, suggesting they may be used as potential biomarkers for footpad lesion development and wound healing process.

Solvent-free fabrication of multi-walled carbon nanotube based flexible pressure sensors for ultra-sensitive touch pad and electronic skin applications

Schematic of the MWCNTs based ultrasensitive touch pad by novel rolling pin and pre-compaction mechanical pressing and its applicability as a user interface in modern electronic devices.

Ganglioside GM3 synthase depletion reverses neuropathic pain and small fiber neuropathy in diet-induced diabetic mice

BackgroundSmall fiber neuropathy is a well-recognized complication of type 2 diabetes and has been shown to be responsible for both neuropathic pain and impaired wound healing. In previous studies, we have demonstrated that ganglioside GM3 depletion by knockdown of GM3 synthase fully reverses impaired wound healing in diabetic mice. However, the role of GM3 in neuropathic pain and small fiber neuropathy in diabetes is unknown.PurposeDetermine whether GM3 depletion is able to reverse neuropathic pain and small fibers neuropathy and the mechanism of the reversal.ResultsWe demonstrate that GM3 synthase knockout and the resultant GM3 depletion rescues the denervation in mouse footpad skin and fully reverses the neuropathic pain in diet-induced obese diabetic mice. In cultured dorsal root ganglia from diet-induced diabetic mice, GM3 depletion protects against increased intracellular calcium influx in vitro.ConclusionsThese studies establish ganglioside GM3 as a new candidate responsible for neuropathic pain and small fiber neuropathy in diabetes. Moreover, these observations indicate that systemic or topically applied interventions aimed at depleting GM3 may improve both the painful neuropathy and the wound healing impairment in diabetes by protecting against nerve end terminal degeneration, providing a disease-modifying approach to this common, currently intractable medical issue.

Connexin 43 contributes to ectopic orofacial pain following inferior alveolar nerve injury.

BackgroundClinically, it is well known that injury of mandibular nerve fiber induces persistent ectopic pain which can spread to a wide area of the orofacial region innervated by the uninjured trigeminal nerve branches. However, the exact mechanism of such persistent ectopic orofacial pain is not still known. The present study was undertaken to determine the role of connexin 43 in the trigeminal ganglion on mechanical hypersensitivity in rat whisker pad skin induced by inferior alveolar nerve injury. Here, we examined changes in orofacial mechanical sensitivity following inferior alveolar nerve injury. Furthermore, changes in connexin 43 expression in the trigeminal ganglion and its localization in the trigeminal ganglion were also examined. In addition, we investigated the functional significance of connexin 43 in relation to mechanical allodynia by using a selective gap junction blocker (Gap27).ResultsLong-lasting mechanical allodynia in the whisker pad skin and the upper eyelid skin, and activation of satellite glial cells in the trigeminal ganglion, were induced after inferior alveolar nerve injury. Connexin 43 was expressed in the activated satellite glial cells encircling trigeminal ganglion neurons innervating the whisker pad skin, and the connexin 43 protein expression was significantly increased after inferior alveolar nerve injury. Administration of Gap27 in the trigeminal ganglion significantly reduced satellite glial cell activation and mechanical hypersensitivity in the whisker pad skin. Moreover, the marked activation of satellite glial cells encircling trigeminal ganglion neurons innervating the whisker pad skin following inferior alveolar nerve injury implies that the satellite glial cell activation exerts a major influence on the excitability of nociceptive trigeminal ganglion neurons.ConclusionsThese findings indicate that the propagation of satellite glial cell activation throughout the trigeminal ganglion via gap junctions, which are composed of connexin 43, plays a pivotal role in ectopic mechanical hypersensitivity in whisker pad skin following inferior alveolar nerve injury.

Incidence and Factors Predicting Skin Burns at the Site of Indifferent Electrode during Radiofrequency Catheter Ablation of Cardiac Arrhythmias.

Radiofrequency catheter ablation (RFA) has become a mainstay for treatment of cardiac arrhythmias. Skin burns at the site of an indifferent electrode patch have been a rare, serious, and likely an underreported complication of RFA. The purpose of this study was to determine the incidence of skin burns in cardiac RFA procedures performed at one institution. Also, we wanted to determine the factors predicting skin burns after cardiac RFA procedures at the indifferent electrode skin pad site. Methods. A retrospective case control study was performed to compare the characteristics in patients who developed skin burns in a 2-year period. Results. Incidence of significant skin burns after RFA was 0.28% (6/2167). Four of the six patients were female and all were Caucasians. Four controls for every case were age and sex matched. Burn patients had significantly higher BMI, procedure time, and postprocedure pain, relative to control subjects (p < 0.05, one-tailed testing). No one in either group had evidence of dispersive pad malattachment. Conclusions. Our results indicate that burn patients had higher BMI and longer procedure times compared to control subjects. These findings warrant further larger studies on this topic.

Antigen-induced arthritis in rats is associated with increased growth-associated protein 43–positive intraepidermal nerve fibres remote from the joint

IntroductionPain in arthritis may be experienced in regions outside the affected joint, and hyperalgesia may even be widespread. The spread of pain is usually attributed to mechanisms in the central nervous system. We investigated whether rats with antigen-induced arthritis (AIA) exhibit peripheral changes in skin innervation remote from the inflamed joint.MethodsAfter immunization, unilateral AIA in the knee joint was induced in rats. Intraepidermal nerve fibre density was determined by immunohistochemical staining for protein gene product 9.5 (PGP 9.5) and for nerve fibres expressing calcitonin gene–related peptide (CGRP), substance P (SP), transient receptor potential vanilloid 1 (TRPV1; the heat and capsaicin receptor), β-tubulin, and growth-associated protein 43 (GAP-43; a marker of regenerating nerve fibres) in paw pad skin and back skin. Cluster of differentiation 11b (CD11b)-positive macrophages and CD3-positive T cells were quantified in skin, and macrophages were quantified in the lumbar dorsal root ganglia. In addition, pain-related behaviour was assessed.ResultsIntraepidermal nerve fibre density (PGP 9.5) and the numbers of fibres expressing CGRP, SP, TRPV1, or β-tubulin did not show a significant change in the acute (3 days) or chronic phase (21 days) of AIA compared with control rats that were only immunized. However, paw skin and back skin revealed a significantly higher number of nerve fibres expressing GAP-43 at both the acute and chronic stages of AIA. The skin of arthritic rats in these regions did not contain a greater density of CD11b and CD3 immune cells than the skin of control rats. Enhanced expression of GAP-43 in nerve fibres of the skin was not related to hyperalgesia in the joint, but it accompanied persistent secondary cutaneous hyperalgesia in the skin remote from the inflamed joint.ConclusionsAlthough the innervation of the skin remote from the joint did not show significant abnormalities of the other nerve fibre markers, the rapid and persistent increase of GAP-43 expression is conspicuous. The data suggest that immune-mediated arthritis is associated with changes in skin innervation remote from the inflamed joint, although the skin is not inflamed, which may contribute to symptoms in nonarticular tissue remote from the affected joint.