Cutaneous Sensitivity Research Articles

Dose-Dependent Effects of Icilin on Thermal Preference in the Hindpaw and Face of Rats

Icilin induces wet dog shakes (WDS) in rodents when injected systemically and activates the cold receptor TRPM8 and putative cold receptor TRPA1. It is assumed that WDS reflect an enhanced cold sensitivity; however, none have examined the relationship between WDS and cutaneous cold sensitivity following systemic icilin. In this study, we sought to characterize the effect of systemic and central icilin administration on WDS and thermal preference with either hindpaw or facial stimulation. It was found that a low dose of icilin (.025 mg), which transiently elevated WDS, decreased preference for cold with hindpaw stimulation (15 and 45 degrees C) when administered ip or it. Intracisternal administration of this dose produced similar results for facial stimulation (10 and 48 degrees C), but had no effect when administered ip. In contrast a high dose of icilin (.25 mg), which persistently elevated WDS, strongly increased preference for cold with hindpaw stimulation and had no effect on thermal preference with facial stimulation. These findings indicate that at the low concentration, systemic and central icilin enhances cold sensitivity, likely via TRPM8 and TRPA1 activation. In contrast, systemic icilin at the high concentration produces peripheral and/or central effects that diminish cold sensitivity, while WDS is maintained at a persistent rate. Icilin is a unique compound that produces dissociable effects on an innate behavior (WDS) and on operant behaviors related to thermal perception. This compound could help clarify the relationship between peripheral cold transduction and the central induction of thermogenesis and nocifensive behaviors, as well as alterations that produce pathological pain.

Prevalence and risk factors for allergic contact dermatitis to topical treatment in atopic dermatitis: a study in 641 children

There is little information regarding the risk of sensitization associated with topical atopic dermatitis (AD) treatment. To assess the frequency of sensitization to topical treatment of AD in children and to determine risk factors associated with skin sensitization. Six hundred and forty-one children with AD were systematically patch tested with seven agents of common topical treatment: chlorhexidine, hexamidine, budesonide, tixocortol pivalate, bufexamac, sodium fusidate and with the current emollient used by the child. The following variables were recorded: age, sex, age at onset of AD, associated asthma, severity of AD, and history of previous exposure to topical agents used in the treatment of AD. Skin prick tests to inhalant and food allergens were used to explore the IgE-mediated sensitization. Forty-one positive patch tests were found in 40 patients (6.2%). Allergens were emollients (47.5%), chlorhexidine (42.5%), hexamidine (7.5%), tixocortol pivalate and bufexamac (2.5% each). Risk factors associated with sensitization to AD treatment were AD severity [OR: 3.3; 95% confidence interval (CI):1.5-7.1 for moderate to severe AD], AD onset before the age of 6 months (OR: 2.7; 95% CI: 1.2-6.1), and IgE-mediated sensitization (OR: 2.5; 95% CI: 1.1-5.9). Topical treatment of AD is associated with cutaneous sensitization. Antiseptics and emollients represent the most frequent sensitizers and may be included in the standard series in AD children when contact dermatitis is suspected. Risk factors associated with sensitization to AD topical treatments are AD severity, early AD onset and IgE-mediated sensitization.

Group II mGluRs inhibit cutaneous nociceptor sensitization

Group II mGluRs inhibit cutaneous nociceptor sensitization

Current understanding of Baboon syndrome

The term Baboon syndrome (BS) was introduced in 1984 to describe the characteristic development of diffuse bright red erythema on the gluteal and anogenital area – resembling the red rump of baboons as a particular clinical form of systemic allergic dermatitis. Additional symmetrical involvement of the upper inner thighs in a V-shaped pattern and major flexures occur frequently. Symmetrical flexural eczema in the absence of gluteal erythema would be better termed systemic allergic dermatitis, and not BS. Approximately 120 cases of BS have been reported to date. Systemic exposure to contact allergens (e.g., mercury) and systemic use of drugs usually without known prior cutaneous sensitization (e.g., amoxicillin) were the main causes. Ethical concern based on the comparison to an animal led to controversy as to whether to continue using the term or to avoid it completely. Such figurative allusions enable a first-glance diagnosis and reflect the terminological richness in dermatology. The acronym SDRIFE (sym...

Toll-like receptor 2 is important for the TH1 response to cutaneous sensitization

Atopic dermatitis and allergic contact dermatitis are skin disorders triggered by epicutaneous sensitization with protein antigens and contact sensitization with haptens, respectively. Skin is colonized with bacteria, which are a source of Toll-like receptor (TLR) 2 ligands. We sought to examine the role of TLR2 in murine models of atopic dermatitis and allergic contact dermatitis. TLR2(-/-) mice and wild-type littermates were epicutaneously sensitized with ovalbumin (OVA) or contact sensitized with oxazolone (OX). Skin histology was assessed by means of hematoxylin and eosin staining and immunohistochemistry. Ear swelling was measured with a micrometer. Cytokine mRNA expression was examined by means of quantitative RT-PCR. Antibody levels and splenocyte secretion of cytokines in response to OVA stimulation were measured by means of ELISA. Dendritic cells were examined for their ability to polarize T-cell receptor/OVA transgenic naive T cells to T(H)1 and T(H)2. In response to OVA sensitization, TLR2(-/-) mice experienced skin infiltration with eosinophils and CD4(+) cells, as well as upregulation of T(H)2 cytokine mRNAs that was comparable with that seen in wild-type littermates. In contrast, epidermal thickening, IFN-gamma expression in the skin, IFN-gamma production by splenocytes, and IgG2a anti-OVA antibody levels were impaired in TLR2(-/-) mice. After OX ear challenge, contact sensitized TLR2(-/-) mice exhibited defective ear swelling with impaired cellular infiltration, decreased epidermal thickening and local IFN-gamma expression, and impaired OX-specific IgG2a responses. Dendritic cells from TLR2(-/-) mice induced significantly lower production of IFN-gamma but normal IL-4 and IL-13 production in naive T cells. These results indicate that TLR2 promotes the IFN-gamma response to cutaneously introduced antigens.

Predictor Factors for Airway Responsiveness during Bronchial Allergen Challenge Tests: Role of Allergen-Specific IgE Levels, Cutaneous Allergen Sensitivity and Non-Specific Airway Hyperresponsiveness

Predictor Factors for Airway Responsiveness during Bronchial Allergen Challenge Tests: Role of Allergen-Specific IgE Levels, Cutaneous Allergen Sensitivity and Non-Specific Airway Hyperresponsiveness

Gastric hypersensitivity induced by oesophageal acid infusion in healthy volunteers

Distal oesophageal acid exposure has been shown to increase visceral sensitivity of the proximal oesophagus via central sensitization. Here we evaluated whether acidification of the distal oesophagus also affects the sensorimotor function of the proximal stomach. A gastric barostat study combined with a 30-min acid (HCl 0.15 mol L(-1)) or saline infusion in the distal oesophagus was performed in 18 healthy volunteers. Gastric and cutaneous sensitivity was assessed before and up to 2 h after the start of infusion. Directly after acid infusion, but not after saline, the threshold for discomfort decreased (-6.4 +/- 1.7 vs 0.4 +/- 0.4 mmHg; P = 0.028) and distension-induced symptoms increased significantly compared with the baseline (122 +/- 49% vs -3 +/- 9%). Cutaneous sensitivity remained unaffected by acid infusion. In contrast, when the infused liquid was aspirated 3 cm more distally, at the level of the lower oesophageal sphincter, the effect of acid infusion on gastric sensitivity was abolished and the increase in distension-induced symptoms was reduced (61 +/- 24%). Distal oesophageal acid infusion induces visceral hypersensitivity without affecting somatic sensitivity arguing against a similar mechanism of central sensitization as observed in non-cardiac chest pain. As reduction of the acid load to the stomach prevented this effect, our findings indicate that either gastric and/or duodenal acidification is involved. It should be emphasized though that aspiration from distal oesophagus may have attenuated the effect by reducing the acid-exposed area or by reducing the contact time.

Diagnóstico etiológico do hirsutismo e implicações para o tratamento

Hirsutism may be defined as the presence of terminal hair in the women, with a male pattern of distribution. The clinical presentation is variable, from isolated hirsutism to the presence of other signs of hyperandrogenism, menstrual irregularities and/or infertility. Hirsutism is related to serum androgens and to the cutaneous sensitivity to these hormones. The most prevalent causes of hirsutism are polycystic ovary syndrome and isolated hirsutism, in the presence of ovulatory cycles. Non-classical congenital adrenal hyperplasia (21-hydroxylase deficiency) and drug-induced hirsutism are less frequent causes. Androgen-secreting neoplasms and Cushing syndrome are rare etiologies related to hirsutism. Diagnostic evaluation should address on identifying the etiology and potential risk for associated comorbidities. The aims of the treatment are: to suppress androgen overproduction, if present; to block androgen action on hair follicles; to identify and treat patients at risk for metabolic disturbances or reproductive neoplasias.

Effects of titanium(iv) ions on human monocyte-derived dendritic cells

Orthopaedic metal implants composed of titanium are routinely used in bone fracture repair and for joint replacement therapies. A considerable fraction of implant recipients are unable to benefit due to implant failure resulting from aseptic loosening, while others may experience cutaneous sensitivity to titanium after implantation. An adaptive immune reactivity towards titanium ions, originating from the biocorrosion of the implants, could play a role. As an initiator of the adaptive immune response, dendritic cells (DC) were studied for uptake and characteristics after titanium exposure. Energy filtered transmission electron microscopy showed uptake of titanium(iv) (Ti(iv)) ions by DCs in vitro and co-localisation with phosphorus-rich cell structures of the DC membranes (phospholipids), cytoplasm (ribosomes and phosphorylated proteins) and the nucleus (DNA). DC maturation and function were investigated by measuring cell surface marker expression by flow cytometry. After exposure, DCs showed a decrease in MHC class II (HLA-DR), co-stimulatory molecules (CD40, CD80 & CD86) and chemokine receptors (CCR) 6 and CCR7 but an increase in CCR4 after Ti(iv) treatment. However, Ti(iv) treated DCs had an increased stimulatory capacity towards allogenic lymphocytes. A Ti(iv) concentration dependant increase of IL-12p70 was observed amidst decrease of the other measured cytokines (TGF-β1 and TGF-β2). Hence, Ti(iv) alters DC properties, resulting in an enhanced T lymphocyte reactivity and deviation towards a Th1 type immune response. This effect may be responsible for the inflammatory side effects of titanium implants seen in patients.

F.65. Toll-like Receptor 2 is Important for the Th1 Response to Cutaneous Sensitization

F.65. Toll-like Receptor 2 is Important for the Th1 Response to Cutaneous Sensitization

Morbidade entre a pós-biópsia de linfonodo sentinela e a dissecção axilar no câncer de mama

The aim of this study was to evaluate the morbidity after sentinel node biopsy (SNB) and axillary dissection with (AD-NS) or without sparing the intercostobrachial nerve (AD-NOS). A prospective cohort study was performed on 108 patients divided into three groups: SNB (n=35), AD-NS (n=36) and AD-NOS (n=37). We evaluated the incidence of sensory loss, pain, lymphedema, seroma formation and infection in the arm homolateral to the breast surgery. Semmes-Weinstein monofilaments were used to assess the sensory loss; brachial perimetry was used to evaluate presence of lymphedema and a pain questionnaire was administered. ANOVA and Kruskal-Wallis statistical tests were used. Bivariate and Multivariate analyses were performed. After surgery at least one complication was reported by 45/108 (41.7%) patients. Pain was the outcome more often reported by patients. In the three groups a significant difference was observed only regarding sensory loss (p=0.04). Pain, lymphedema, and sensory loss were more frequently found in the AD-NOS group. No significant difference was observed between SNB and AD-NS groups. Semmes-Weinstein monofilaments showed preservation of cutaneous sensitivity in 28/35 patients from the SNB group, in 25/36 patients from AD-NS group but in only 10/37 patients from AD-NOS group (p<0.001). The ICB section is associated with higher sensory loss, with statistically significant difference between the groups that were not shown to be significant with the others complications.

High force reaching task induces widespread inflammation, increased spinal cord neurochemicals and neuropathic pain

Repetitive strain injuries (RSI), which include several musculoskeletal disorders and nerve compression injuries, are associated with performance of repetitive and forceful tasks. In this study, we examined in young, adult Sprague-Dawley rats, the effects of performing a voluntary, moderate repetition, high force (MRHF; nine reaches/min; 60% maximum pulling force) task for 12 weeks on motor behavior and nerve function, inflammatory responses in forearm musculoskeletal and nerve tissues and serum, and neurochemical immunoexpression in cervical spinal cord dorsal horns. We observed no change in reach rate, but reduced voluntary participation and grip strength in week 12, and increased cutaneous sensitivity in weeks 6 and 12, the latter indicative of mechanical allodynia. Nerve conduction velocity (NCV) decreased 15% in the median nerve in week 12, indicative of low-grade nerve compression. ED-1 cells increased in distal radius and ulna in week 12, and in the median nerve and forearm muscles and tendons in weeks 6 and 12. Cytokines IL-1α, IL-1β, TNF-α, and IL-10 increased in distal forearm bones in week 12, while IL-6 increased in tendon in week 12. However, serum analysis revealed only increased TNF-α in week 6 and macrophage inflammatory protein 3a (MIP3a) in weeks 6 and 12. Lastly, Substance P and neurokinin-1 were both increased in weeks 6 and 12 in the dorsal horns of cervical spinal cord segments. These results show that a high force, but moderate repetition task, induced declines in motor and nerve function as well as peripheral and systemic inflammatory responses (albeit the latter was mild). The peripheral inflammatory responses were associated with signs of central sensitization (mechanical allodynia and increased neurochemicals in spinal cord dorsal horns).

Association of Lower Limb Cutaneous Sensitivity with Gait Speed in the Elderly

To examine the association of fast-adapting receptor-mediated vibrotactile sensitivity and slow-adapting receptor-mediated pressure sensitivity with self-selected usual gait speed and gait speed over a challenging narrow (20 cm wide) course. Participants from the population-based older cohort of the Health ABC study were included (n = 1721; age: 76.4 +/- 2.8 yrs). Usual gait speed over 6 m and gait speed over a 6-m narrow course were measured. Vibration perception threshold (100 Hz) was measured on the plantar surface, and monofilament testing (1.4 and 10 g) was performed on the dorsum of the great toe. Covariates including knee extensor torque, standing balance, visual acuity and contrast sensitivity, knee pain, depressive symptoms, high fasting glucose levels, and peripheral arterial disease were evaluated. Vibrotactile and monofilament sensitivity were significantly worse in slower gait speed groups in both walking conditions (P < 0.001 to P = 0.015). Adjusting for covariates, vibrotactile (P < 0.001) but not monofilament sensitivity (P = 0.655) was independently associated with self-selected normal gait speed. Neither sensory function was associated with narrow-base gait speed. In the elderly, poor lower limb vibrotactile sensitivity measured on the plantar surface of the great toe, but not the pressure sensitivity as measured by monofilament testing on the dorsum of the great toe, is independently associated with slower self-selected normal gait speed. Narrow-based walking seems to depend on other neuromuscular mechanisms.

Drug‐elicited systemic allergic (contact) dermatitis – update and possible pathomechanisms

An allergic dermatitis reaction may develop after systemic exposure to a hapten that reaches the skin through haematogenous transport. This condition can be observed with and without previous cutaneous sensitization to the hapten but has traditionally been described following topical exposure. A heterogeneous clinical picture, in combination with limited insight to its pathomechanisms, makes such systemic reactions an area in need of further study. This article summarizes knowledge about systemic dermatitis elicited by drugs, with a special emphasis on possible pathomechanisms. A list of putative pathomechanisms is offered for future research. Literature was examined using PubMed-MEDLINE, EMBASE, Biosis, and Science Citation Index. Based on the literature, it is likely that humoral type 3, delayed-type hypersensitivity, and drug-driven (i.e. p-i concept) reactions are involved. As commonly used terms may be misleading because skin contact is not a prerequisite, we suggest that the term 'systemic allergic dermatitis' should be used in the future.

Early loss of peptidergic intraepidermal nerve fibers in an STZ-induced mouse model of insensate diabetic neuropathy

Peptidergic and nonpeptidergic nociceptive neurons represent parallel yet distinct pathways of pain transmission, but the functional consequences of such specificity are not fully understood. Here, we quantified the progression of peptidergic and nonpeptidergic axon loss within the epidermis in the setting of a dying-back neuropathy induced by diabetes. STZ-induced diabetic MrgD mice heterozygous for green fluorescent protein (GFP) in nonpeptidergic DRG neurons were evaluated for sensitivity to mechanical and noxious thermal and chemogenic stimuli 4 or 8 weeks post-STZ. Using GFP expression in conjunction with PGP9.5 staining, nonpeptidergic (PGP+/GFP+) and peptidergic (PGP+/GFP−) intraepidermal nerve fibers (IENFs) were quantified at each time point. At 4 weeks post-STZ, nonpeptidergic epidermal innervation remained unchanged while peptidergic innervation was reduced by 40.6% in diabetic mice. By 8 weeks post-STZ, both nonpeptidergic innervation and peptidergic innervation were reduced in diabetic mice by 34.1% and 43.8%, respectively, resulting in a 36.5% reduction in total epidermal IENFs. Behavioral deficits in mechanical, thermal, and chemogenic sensitivity were present 4 weeks post-STZ, concomitant with the reduction in peptidergic IENFs, but did not worsen over the next 4 weeks as nonpeptidergic fibers were lost, suggesting that the early reduction in peptidergic fibers may be an important driving force in the loss of cutaneous sensitivity. Furthermore, behavioral responses were correlated at the 4 week time point with peptidergic, but not nonpeptidergic, innervation. These results reveal that peptidergic and nonpeptidergic nociceptive neurons are differentially damaged by diabetes, and behavioral symptoms are more closely related to the losses in peptidergic epidermal fibers.

Altered behavior and digestive outcomes in adult male rats primed with minimal colon pain as neonates

BackgroundNeonatal colon irritation (CI; pain or inflammation) given for 2 weeks prior to postnatal day 22 (PND22), causes long-lasting functional disorders in rats that can be seen 6 months after the initial insult. This study looked at the effect of varying the frequency and duration of neonatal CI on the rate of growth, digestive outcomes, exploratory activity, and colon and skin sensitivity in adult rats.MethodsMale Sprague-Dawley rats were given CI using repeated colorectal distension (CRD) at different time intervals and for varying durations starting at PND 8, 10 or 14. Control rats were handled by the investigator without any intracolonic insertion. Further experiments were done on adult rats. Digestive outcomes (food and water consumption, fecal and urinary outputs) were measured using metabolic cages. Exploratory behavior was measured using digital video tracking in an open field. Cutaneous sensitivity was assessed by measuring the responses to mechanical and heat stimuli applied to the shaved abdomen or hind paws. Visceral sensitivity was measured by recording electromyographic responses, under light isoflurane anesthesia, from the external oblique muscles in response to CRD.ResultsNo significant weight differences were observed between CI and control rats. Exploratory behavior was reduced in rats with neonatal CI compared to control. Digestive outputs and somatic and visceral sensitivity changed between different treatment groups with earlier and more frequent insults yielding a higher deviation from normal.ConclusionThe diversity of behavioral and digestive symptoms in these rats parallels the diversity of symptoms in patients with functional gastrointestinal disorders and is consistent with global plastic changes affecting more than one system in the organism.

Oral desensitization in children with immunoglobulin E‐mediated cow’s milk allergy – follow‐up at 4 yr and 8 months

Until now, the basic treatment for food allergy has been to avoid the offending item. This approach is difficult in the case of common foods and in the case where there is a risk of severe reaction after consuming the offending food, even inadvertently. This is the follow-up of a previous study aimed at desensitizing 21 children with immunoglobulin E (IgE)-mediated cow's milk (CM) allergy. This protocol was totally or partially successful in 85% of cases, but failed in the remaining 15%. Our aims were to study the long-term effectiveness and safety of oral CM desensitization, and the prognostic value of Skin Prick Test (SPT) and specific serum CM IgE. The 21 children were called back (one dropped out). The allergic history and other information on CM intake over the last 4-5 yr were recorded. Children underwent SPT, and end-point SPT, with casein and alpha-lactoalbumin. Specific CM IgE was also measured. At follow-up, 14/20 children totally (n = 13, 65%) or partially (n = 1, 5%) tolerated CM. None of the recalled children reported use of emergency care. SPT positivity to casein and/or alpha-lactoalbumin decreased significantly (p < 0.01), and all the negative SPT referred to the tolerant children. Cutaneous sensitivity to both casein and alpha-lactoalbumin (end-point SPT) significantly decreased after the 6-month desensitization period of the previous study (p < 0.001), but did not decrease significantly at follow-up. A significant reduction of serum-specific CM IgE was also observed (p < 0.05). Clinical tolerance induced by oral CM desensitization persists in time. Negativization of SPT and reduction of specific CM IgE could be considered prognostic indicators of CM tolerance. Oral CM desensitization seems to be a promising method to treat CM food allergy. This protocol is time-consuming but offers the advantage that it can be performed at home. This methodology must only be used by trained staff.

Melanocortin-1 Receptor Signaling Markedly Induces the Expression of the NR4A Nuclear Receptor Subgroup in Melanocytic Cells

The melanocortin-1 receptor (MCIR) is a G-protein-coupled receptor expressed primarily in melanocytes and is known to play a pivotal role in the regulation of pigmentation in mammals. In humans MC1R has been found to be highly polymorphic with several functional variants associated with the phenotype of red hair color and fair skin, cutaneous UV sensitivity, and increased risk of developing melanoma and non-melanoma skin cancer. Recent evidence suggests that MC1R plays a photo-protective role in melanocytes in response to UV irradiation. Relatively few genetic targets of MC1R signaling have been identified independent of the pigmentation pathway. Here we show that MC1R signaling in B16 mouse melanoma cells and primary human melanocytes rapidly, and transiently, induces the transcription of the NR4A subfamily of orphan nuclear receptors. Furthermore, primary human melanocytes harboring homozygous RHC variant MC1R alleles exhibited an impaired induction of NR4A genes in response to the potent MC1R agonist (Nle4,D-Phe7)-alpha-melanocyte-stimulating hormone. Using small interference RNA-mediated attenuation of NR4A1 and NR4A2 expression in melanocytes, the ability to remove cyclobutane pyrimidine dimers following UV irradiation appeared to be impaired in the context of MC1R signaling. These data identify the NR4A receptor family as potential mediators of an MC1R-coordinated DNA damage response to UV exposure in melanocytic cells.

Selected Function Performance in Healthy Young and Old, as well as People with Peripheral Neuropathy

Peripheral Neuropathy (PN) is characterized by altered cutaneous sensitivity. While individuals with PN present with an increased risk of falls, little is known about its effects on common measures of physical function. The PURPOSE of this study was to compare performance in selected physical function in people with PN, healthy agematched controls (HO) and young adults (HY). METHODS: Thirteen people with diagnosed PN (11 women, 2 men, mean age = 66.1 ± 25.1 years; height = 167.7 ± 16.4 cm, body mass = 69.9 ± 16.6 kg), 13 HO (8 women, 5 men, mean age = 60.3 ± 6.7 years; height =173.2 ± 20.8 cm, body mass = 78.0 ± 33.6 kg), and 13 HY (10 women, 3 men, mean age = 21.4 ± 1.6 years; height =168.5 ± 14.4 cm, body mass = 65.7 ± 44.6 kg) signed a consent form approved by the IRB. Eyes-closed standing balance was evaluated by the average velocity (VEL, cm/s) and the area enclosing 95% (A95, cm2) of the body center of pressure. Knee strength (Nm) was assessed by maximum isokinetic (60 deg/s) knee extensor (KE) and flexor peak torque (KF). Functional capacity and mobility were measured by the six minute walk (6MW, m) test and the timed up-and-go (TUG, sec) test, respectively. Sensation of 5 foot sole locations was evaluated with a 5.07 gauge monofilament. ANOVA was used for comparison. RESULTS: The PN exhibited severe loss of sensitivity in the five tested sites as compared to the HO and HY (PN = 3.4 ± 3.4, HO = 4.9 ± .9, HY = 5 ± 0 sites, p < .001). The PN walked significantly less distance in the 6MW compared to the HO and HY (PN = 485 ± 114, HO = 586 ± 107, HY = 604 ± 72, p < .001). PN took significantly longer in completing TUG tests (PN = 8.1 ± .6, HO = 6.0 ± .2, HY = 5.2 ± .2). A95 and VEL measurements demonstrated that the PN (10.8 ± 3.1, 3.2 ± .4) was different (P < .02, P < .003) from the HY (3.1 ± .9, 1.4 ± .1). No difference was observed between the HO (4.4 ± .8, 2.3 ± .4) and the other groups. KE was significantly lower in the PN compared to the HY, yet no difference was observed between the HO and the other groups (PN = 97 ± 21, HO = 127 ± 21, HY = 153 ± 22, p < .04). No significant group differences were observed in KF. CONCLUSIONS: Minimal difference was observed between the performance of HY and HO, suggesting that normal aging has little effect on the tested physical function. PN is a debilitating movement disorder that has substantial effects on weight-bearing measures of physical function.

Peripheral Neuropathy Alters Variability but not Finite-Time Lyapunov Exponents during Treadmill Walking

Peripheral neuropathy (PN) is marked by diminished plantar cutaneous sensitivity, reduced preferred walking speed (PWS), and increased risk of falls. Predisposition to falls may result from an inability to adapt to challenging walking speeds. The PURPOSE: of this study was to compare the dynamics of treadmill walking at different speeds between individuals with PN and age-matched controls. METHODS: Eleven individuals with PN (mean ± SD age=67.0 ± 10.9 yr, height =172 ± 11 cm, body mass=86.8 ± 23.6 kg) and 11 healthy controls (age=69.1 ± 10.0 yr, height=168 ± 6 cm, body mass=83.0 ± 18.8 kg) gave informed consent as approved by the university's IRB. The 6-min walk test was used to determine "maximal walking speed" (100%MWS). Multiple treadmill walking trials were then completed at 100%MWS, 80%MWS, and 60%MWS. During the middle 2 min of each trial, motion analysis (60 Hz) was used to collect sagittal plane hip, knee, and ankle joint kinematics. Stride duration variability (SDvar) was calculated from 30 consecutive strides. Joint angle variability (JTvar) was calculated for each joint from the ensemble curves of the same 30 strides. Short-and long-term Finite-Time Lyapunov Exponents (ST, LT) were computed for each joint from ensemble curves of 100 consecutive strides. Factorial ANOVA with repeated measures was used for statistical analysis. Tukey's pos-hoc tests were used wherever appropriate. RESULTS: In general, faster walking speeds were associated with increased SDvar, JTvar, ST and LT. The PN group walked slower than the control group (100%MWS=1.25 ± 0.17 vs. 1.45 ± 0.29 m/s, F1,21=4.41, p<0.001). Despite controlling for the variance in walking speed, the PN group exhibited increased SDvar (32.9 ± 2.2 vs. 23.7 ± 1.4 ms, F1, 65=6.77, p=.02) and JTvar (2.64 ± 0.10 vs. 1.87 ± 0.07 deg, F1, 65=29.1, p=.01). No group or group × speed interactive effects were observed for ST or LT. CONCLUSIONS: Compared to controls, the PN group exhibited increased variability (SDvar and JTvar) over and above that elicited by group differences in walking speed. However, no difference in the time dependent Lyapunov Exponents were observed. While effects were not exaggerated when walking at challenging speeds, the results nevertheless highlight the disturbed control of walking in this population.