Anxiety- but not depressive-like behaviors are related to facial hyperalgesia in a model of trigeminal neuropathic pain in rats.

Trigeminal neuralgia (TN) is a painful condition characterized by excruciating facial pain, which has a serious impact on quality of life. Depression and anxiety have been commonly associated with TN, but clinical studies report that these comorbidities are frequently underdiagnosed and undertreated in TN patients. Herein it was investigated if rats submitted to the infraorbital nerve constriction (CION), a model of trigeminal neuropathic pain, would display anxiety- and depressive-like behaviors in addition to the facial sensory changes in different time points after the nerve injury. CION rats developed facial heat hyperalgesia on day 5 after the nerve injury, but at this time point the time spent and the number of entries on open arms in the elevated plus maze (EPM) and the time spent on the lit compartment of light-dark transition test (LDT) was not statistically significant between SHAM and CION groups, suggesting that 5 days after CION animals do not display anxiety-like behavior. On the other hand, around 50% of CION rats developed mechanical allodynia on day 15 postsurgery and the analysis of the time spent and the number of entries on open arms on EPM and the time spent on lit compartment of LDT revealed that only CION-allodynic animals displayed anxiety-like behavior when compared to the SHAM group. The depressive-like behavior was assessed by measuring the time of immobility on the forced swim test (FST) and sucrose preference (SP) in rats previously tested for heat (day 5) and mechanical allodynia (days 15, 30 and 45) induced by CION. The evaluation of immobility time on FST and sucrose preference consumption revealed that both CION rats did not displayed depressive- and anhedonic-like behavior at any time point evaluated. Altogether, these results demonstrate that trigeminal neuropathic pain in rats leads to the development of anxiety-, but not depressive-like behavior, suggesting that the CION model represents a methodology that allows the study of drugs targeting both pain and anxiety.

Blockade of Neuroglobin Reduces Protection of Conditioned Medium from Human Mesenchymal Stem Cells in Human Astrocyte Model (T98G) Under a Scratch Assay.

Previous studies have indicated that paracrine factors (conditioned medium) increase wound closure and reduce reactive oxygen species in a traumatic brain injury in vitro model. Although the beneficial effects of conditioned medium from human adipose tissue-derived mesenchymal stem cells (hMSCA-CM) have been previously suggested for various neurological diseases, their actions on astrocytic cells are not well understood. In this study, we have explored the effect of hMSCA-CM on human astrocyte model (T98G cells) subjected to scratch assay. Our results indicated that hMSCA-CM improved cell viability, reduced nuclear fragmentation, attenuated the production of reactive oxygen species, and preserved mitochondrial membrane potential and ultrastructural parameters. In addition, hMSCA-CM upregulated neuroglobin in T98G cells and the genetic silencing of this protein prevented the protective action of hMSCA-CM on damaged cells, suggesting that neuroglobin is mediating, at least in part, the protective effect of hMSCA-CM. Overall, this evidence suggests that the use of hMSCA-CM is a promising therapeutic strategy for the protection of astrocytic cells in central nervous system (CNS) pathologies.

Kinin Receptors Sensitize TRPV4 Channel and Induce Mechanical Hyperalgesia: Relevance to Paclitaxel-Induced Peripheral Neuropathy in Mice.

Kinin B1 (B1R) and B2 receptors (B2R) and the transient receptor potential vanilloid 4 (TRPV4) channel are known to play a critical role in the peripheral neuropathy induced by paclitaxel (PTX) in rodents. However, the downstream pathways activated by kinin receptors as well as the sensitizers of the TRPV4 channel involved in this process remain unknown. Herein, we investigated whether kinins sensitize TRPV4 channels in order to maintain PTX-induced peripheral neuropathy in mice. The mechanical hyperalgesia induced by bradykinin (BK, a B2R agonist) or des-Arg9-BK (DABK, a B1R agonist) was inhibited by the selective TRPV4 antagonist HC-067047. Additionally, BK was able to sensitize TRPV4, thus contributing to mechanical hyperalgesia. This response was dependent on phospholipase C/protein kinase C (PKC) activation. The selective kinin B1R (des-Arg9-[Leu8]-bradykinin) and B2R (HOE 140) antagonists reduced the mechanical hyperalgesia induced by PTX, with efficacies and time response profiles similar to those observed for the TRPV4 antagonist (HC-067047). Additionally, both kinin receptor antagonists inhibited the overt nociception induced by hypotonic solution in PTX-injected animals. The same animals presented lower PKCε levels in skin and dorsal root ganglion samples. The selective PKCε inhibitor (εV1-2) reduced the hypotonicity-induced overt nociception in PTX-treated mice with the same magnitude observed for the kinin receptor antagonists. These findings suggest that B1R or B2R agonists sensitize TRPV4 channels to induce mechanical hyperalgesia in mice. This mechanism of interaction may contribute to PTX-induced peripheral neuropathy through the activation of PKCε. We suggest these targets represent new opportunities for the development of effective analgesics to treat chronic pain.

Temperament, behavior, body temperature, heart and respiratory rate of sheep trained with tactile stimulation and halter walking / Temperamento, comportamento, temperatura corporal, frequência cardíaca e respiratória de ovinos treinados com estímulo tátil e deslocamento com auxílio de cabresto

O objetivo desse estudo foi avaliar a influência dos treinamentos com estímulo tátil e deslocamento com auxílio de cabresto no temperamento, fisiologia, comportamento e peso corporal de ovinos. Um total de 80 ovinos, machos e fêmeas, das raças Morada Nova (MN) e Santa Inês (SI), com idade inicial de seis a oito meses, foram treinados com estímulo tátil (TS), deslocamento com auxílio de cabresto (HW) ou estímulo tátil e deslocamento com auxílio de cabresto (TS+HW). Os animais do grupo controle (C) não foram submetidos a nenhum tipo de treinamento. Os aspectos comportamentais foram mensurados no teste de campo aberto, para quantificar as variáveis movimentação, vocalização, tentativa de fuga e cavar chão, enquanto no teste de temperamento foram dados escores de temperamento para cada animal. Os animais foram pesados e foram aferidas as temperaturas retais, frequências cardíacas e respiratórias. Os machos foram mais reativos ao humano do que as fêmeas. Os animais treinados com TS foram menos reativos no teste de temperamento, enquanto os animais mais reativos eram machos SI dos tratamentos C e TS+HW. Machos dos tratamentos C e HW foram os mais pesados durante o estudo. Os animais do grupo controle mostraram maiores médias para frequência cardíaca e temperatura retal, enquanto animais treinados com TS e HW mostraram os menores valores. Fêmeas MN treinadas com TS e TS+HW se movimentaram mais durante o teste de campo aberto, enquanto fêmeas SI do grupo controle se movimentaram menos. Os animais da raça SI vocalizaram mais durante o teste de campo aberto, tanto do tratamento C quanto do TS+HW. Os animais da raça MN do grupo C vocalizaram menos. Ovinos treinados com estímulo tátil se mostraram mais dóceis. O treinamento com estímulo tátil e deslocamento com auxílio de cabresto em ovinos das raças Morada Nova e Santa Inês influenciou a frequência cardíaca, a temperatura retal, a movimentação, a...(AU)

This study aimed to evaluate the influence of tactile stimulation and halter walking trainings in the temperament, physiology, behavior and body weight of sheep. A total of 80 sheep, males and females, of the Morada Nova (MN) and Santa Ines (SI) breeds, with initial ages of six to eight months, were trained with tactile stimulation (TS), halter walking (HW) or tactile stimulation and halter walking (TS+HW). The control (C) animals were not submitted to any kind of training. The behavioral aspects were measured by application of a open-field test, to quantify the traits movement, vocalization, escape attempt and digging, and the temperament test, with assignment of a temperament score for each animal. The animals were weighed and rectal temperature, heart rate and respiratory rate were measured. Males were more reactive than females to human. Animals trained with TS were the least reactive in the temperament test, while the most reactive animals were SI male from C and TS+HW treatments. Males of treatments C and HW were the heaviest during the study. The animals in the control group showed higher averages for heart rate and rectal temperature, while animals trained with TS and HW showed the lowest values. Females MN trained with TS and TS+HW moved more during the open-field test, while the SI females of the control group moved less. The SI animals vocalized more during the open-field test, both from treatment C and from TS+HW. The MN animals from C treatment vocalized less. Sheep trained with tactile stimulation were more docile. The training with tactile stimulation and halter walking in Santa Ines and Morada Nova sheep influenced the heart rate, rectal temperature, moviment, vocalization, escape attempt and body weight.(AU)

Temperament, behavior, body temperature, heart and respiratory rate of sheep trained with tactile stimulation and halter walking / Temperamento, comportamento, temperatura corporal, frequência cardíaca e respiratória de ovinos treinados com estímulo tátil e deslocamento com auxílio de cabresto

O objetivo desse estudo foi avaliar a influência dos treinamentos com estímulo tátil e deslocamento com auxílio de cabresto no temperamento, fisiologia, comportamento e peso corporal de ovinos. Um total de 80 ovinos, machos e fêmeas, das raças Morada Nova (MN) e Santa Inês (SI), com idade inicial de seis a oito meses, foram treinados com estímulo tátil (TS), deslocamento com auxílio de cabresto (HW) ou estímulo tátil e deslocamento com auxílio de cabresto (TS+HW). Os animais do grupo controle (C) não foram submetidos a nenhum tipo de treinamento. Os aspectos comportamentais foram mensurados no teste de campo aberto, para quantificar as variáveis movimentação, vocalização, tentativa de fuga e cavar chão, enquanto no teste de temperamento foram dados escores de temperamento para cada animal. Os animais foram pesados e foram aferidas as temperaturas retais, frequências cardíacas e respiratórias. Os machos foram mais reativos ao humano do que as fêmeas. Os animais treinados com TS foram menos reativos no teste de temperamento, enquanto os animais mais reativos eram machos SI dos tratamentos C e TS+HW. Machos dos tratamentos C e HW foram os mais pesados durante o estudo. Os animais do grupo controle mostraram maiores médias para frequência cardíaca e temperatura retal, enquanto animais treinados com TS e HW mostraram os menores valores. Fêmeas MN treinadas com TS e TS+HW se movimentaram mais durante o teste de campo aberto, enquanto fêmeas SI do grupo controle se movimentaram menos. Os animais da raça SI vocalizaram mais durante o teste de campo aberto, tanto do tratamento C quanto do TS+HW. Os animais da raça MN do grupo C vocalizaram menos. Ovinos treinados com estímulo tátil se mostraram mais dóceis. O treinamento com estímulo tátil e deslocamento com auxílio de cabresto em ovinos das raças Morada Nova e Santa Inês influenciou a frequência cardíaca, a temperatura retal, a movimentação, a...

This study aimed to evaluate the influence of tactile stimulation and halter walking trainings in the temperament, physiology, behavior and body weight of sheep. A total of 80 sheep, males and females, of the Morada Nova (MN) and Santa Ines (SI) breeds, with initial ages of six to eight months, were trained with tactile stimulation (TS), halter walking (HW) or tactile stimulation and halter walking (TS+HW). The control (C) animals were not submitted to any kind of training. The behavioral aspects were measured by application of a open-field test, to quantify the traits movement, vocalization, escape attempt and digging, and the temperament test, with assignment of a temperament score for each animal. The animals were weighed and rectal temperature, heart rate and respiratory rate were measured. Males were more reactive than females to human. Animals trained with TS were the least reactive in the temperament test, while the most reactive animals were SI male from C and TS+HW treatments. Males of treatments C and HW were the heaviest during the study. The animals in the control group showed higher averages for heart rate and rectal temperature, while animals trained with TS and HW showed the lowest values. Females MN trained with TS and TS+HW moved more during the open-field test, while the SI females of the control group moved less. The SI animals vocalized more during the open-field test, both from treatment C and from TS+HW. The MN animals from C treatment vocalized less. Sheep trained with tactile stimulation were more docile. The training with tactile stimulation and halter walking in Santa Ines and Morada Nova sheep influenced the heart rate, rectal temperature, moviment, vocalization, escape attempt and body weight.

Review of Physical Urticarias and Testing Methods.

PURPOSE OF REVIEW: This review aims to update the information available on the prevalence, clinical picture, diagnostic methods, and treatment of urticarias induced by external physical stimuli. RECENT FINDINGS: Physical urticarias are present in up to 5% of the general population, and in 10 to 50% of patients with chronic urticaria. Recent investigations have provided evidence that the presence of physical urticaria alone or when comorbid with chronic spontaneous urticaria is associated with a worse prognosis and duration. Most frequent subtypes of physical urticaria are dermographism and delayed pressure urticaria. The diagnosis is established through specific provocation tests and the management encompasses avoidance measures, pharmacologic therapy with nonsedating antihistamines, and alternative medications in refractory cases.

Noxious mechanical heterotopic stimulation induces inhibition of the spinal dorsal horn neuronal network: analysis of spinal somatosensory-evoked potentials.

Most of the endogenous pain modulation (EPM) involves the spinal dorsal horn (SDH). EPM including diffuse noxious inhibitory controls have been extensively described in oligoneuronal electrophysiological recordings but less attention had been paid to responses of the SDH neuronal population to heterotopic noxious stimulation (HNS). Spinal somatosensory-evoked potentials (SEP) offer the possibility to evaluate the neuronal network behavior, reflecting the incoming afferent volleys along the entry root, SDH interneuron activities and the primary afferent depolarization. SEP from de lumbar cord dorsum were evaluated during mechanical heterotopic noxious stimuli. Sprague-Dawley rats (n = 12) were Laminectomized (T10-L3). The sural nerve of the left hind paw was electrically stimulated (5 mA, 0.5 ms, 0.05 Hz) to induce lumbar SEP. The HNS (mechanic clamp) was applied sequentially to the tail, right hind paw, right forepaw, muzzle and left forepaw during sural stimulation. N wave amplitude decreases (-16.6 %) compared to control conditions when HNS was applied to all areas of stimulation. This effect was more intense for muzzle stimulation (-23.5 %). N wave duration also decreased by -23.6 %. HNS did not change neither the amplitude nor the duration of the P wave but dramatically increases the dispersion of these two parameters. The results of the present study strongly suggest that a HNS applied to different parts of the body is able to reduce the integrated electrical response of the SDH, suggesting that not only wide dynamic range neurons but many others in the SDH are modulated by the EPM.

A D2-like receptor family agonist produces analgesia in mechanonociception but not in thermonociception at the spinal cord level in rats.

The administration of dopaminergic drugs produces analgesia in individuals experiencing different types of pain. Analgesia induced by these drugs at the spinal cord level is mediated by D2-like agonists, which specifically inhibit the detection of nociceptive stimuli by sensory afferents. The extent of the analgesia provided by spinal dopamine agonists remains controversial, and the cellular mechanism of this analgesic process is poorly understood. The objective of this study was to evaluate the analgesic effect of quinpirole, a D2-like agonist, based on two nociceptive tests and at various doses that were selected to specifically activate dopamine receptors. We found that intrathecal quinpirole administration produces analgesia of mechanical but not thermal nociception and that the analgesic effect of quinpirole is reversed by a mix of D2, D3, and D4 receptor-specific antagonists, suggesting that the activation of all D2-like receptors is involved in the analgesia produced by intrathecal quinpirole. The differential effect on thermal and mechanical nociception was also tested upon the activation of µ-opioid receptors. As reported previously, low doses of the µ-opioid receptor agonist DAMGO produced analgesia of only thermonociception. This evidence shows that a D2-like receptor agonist administered at the spinal cord level produces analgesia specific to mechanonociception but not thermonociception.

Effectiveness of hip muscle strengthening in patellofemoral pain syndrome patients: a systematic review

Introduction: Patellofemoral pain syndrome (PFPS) is characterized by anterior knee pain, which may limit the performance of functional activities. The influence of hip joint motion on the development of this syndrome has already been documented in the literature. In this regard, studies have investigated the effectiveness of hip muscle strengthening in patients with PFPS. Objectives: The aims of this systematic review were (1) to summarize the literature related to the effects of hip muscle strengthening on pain intensity, muscle strength, and function in individuals with PFPS and (2) to evaluate the methodological quality of the selected studies. Method: A search for randomized controlled clinical trials was conducted using the following databases: Google Scholar, MEDLINE, PEDro, LILACS, and SciELO. The selected studies had to distinguish the effects of hip muscle strengthening in a group of patients with PFPS, as compared to non-intervention or other kinds of intervention, and had to investigate the following outcomes: pain, muscle strength, and function. The methodological quality of the selected studies was analyzed by means of the PEDro scale. Results: Seven studies were selected. These studies demonstrated that hip muscle strengthening was effective in reducing pain. However, the studies disagreed regarding the treatments' ability to improve muscle strength. Improvement in functional capabilities after hip muscle strengthening was found in five studies. Conclusion: Hip muscle strengthening is effective in reducing the intensity of pain and improving functional capabilities in patients with PFPS, despite the lack of evidence for its ability to increase muscle strength. .

Avaliação da reatividade de equinos durante o manejo e na presença de estímulo desconhecido / Evaluation of the reactivity of horses during handling and in the presence of unknown stimulus

O estudo teve como objetivo adaptar a avaliação comportamental dos equinos durante manejos de rotina como metodologia da averiguação da reatividade dos animais. Para isso foram realizados dois experimentos, o primeiro identificou as variáveis relacionadas à expressão da reatividade dos equinos durante manejos de rotina; e o segundo avaliou a reatividade dos equinos frente à presença de um estímulo sonoro desconhecido durante o manejo habitual de escovação. O primeiro desenvolvido em um criatório de equinos da raça Lusitano situado na cidade de Itapira, SP, avaliou 364 animais de diferentes idades, constituindo 188 éguas adultas reprodutoras e 176 potros (machos e fêmeas), durante os manejos de casqueamento, aplicação de vermífugo, vacinação, tosa, manejos reprodutivos como, palpação, rufiação, lavagem para cobertura, cobertura, inseminação artificial e infusão uterina. A reatividade foi estimada pela atribuição de escores aos comportamentos de: movimentação; posição das orelhas e dos olhos, respiração, vocalização, velocidade de fuga, e micção. Também foi conferida uma variável resposta denominada de reatividade, com variação de escore de reatividade 1 (atribuída ao animal não reativo ou calmo) até escore de reatividade 4 (atribuída ao animal muito reativo ou agressivo). A verificação das possíveis variáveis (idade, sexo e comportamento), que explicam a variável resposta (reatividade), foi feita pelo modelo ordinal de odds proporcionais. Este comprovou que os maiores escores de reatividade estão associados aos potros (P<0,01). [...] Os animais do tratamento com estímulo desconhecido apresentaram maior reatividade (P<0,01). Os dias do período experimental influenciaram a reatividade dos animais da categoria A (P<0,01), com diminuição das possibilidades dos animais dessa idade apresentarem maior reatividade.

The study aimed to adapt the evaluation of the horses/' behavior during routine managements as a method of investigating the reactivity of animals. Two experiments were conducted; the first recognized the variables related to the expression of the reactivity of horses during handling, and the second was done during usual brushing management against the presence of an unknown sonorous stimulus. The first experiment was developed in a farm of Lusitano horses located in Itapira, SP, where 364 animals of different ages were evaluated, representing 188 adult mares and 176 foals (males and females) during the managements hooves trimming, vermifuge application, vaccination, leathering, breeding managements as palpation, ruffian presentation, wash to cover, cover, artificial insemination and uterine infusion. The reactivity was estimated by assigning scores to behaviors: movement, position of ears and eyes, breathing, vocalization, flight speed, and urination. A response variable called reactivity was attributed to the animal, ranging from reactivity score 1 (attributed to the animal not reactive or calm) to reactivity score 4 (attributed to the animal very reactive or aggressive). The verification of the possible variables (age, sex, and behavior), which explain the response variable (reactivity), was taken by ordinal proportional odds model. This proved that higher reactivity scores are associated with foals. Likewise it was proven that the higher scores of the behaviors of movement, position of ears and eyes and breathing and vocalization scores of no less than 2 are associated with higher reactivity scores (P<0.01). [...] The animals of the treatment unknown stimuli showed greater reactivity (P<0.01). The days of the experimental period influenced the reactivity of animals in category A (P<0,01), with a decrease in the possibilities of animals in this category to have a higher reactivity.

Antinociception induced by motor cortex stimulation: somatotopy of behavioral response and profile of neuronal activation.

Motor cortex stimulation (MCS) is used as a therapy for patients with refractory neuropathic pain. Experimental evidence suggests that the motor cortex (MC) is involved in the modulation of normal nociceptive response, but the underlying mechanisms have not been clarified yet. In previous studies, we demonstrated that MCS increases the nociceptive threshold of naive conscious rats by inhibiting thalamic sensory neurons and disinhibiting the neurons in periaqueductal gray (PAG), with the involvement of the opioid system. The aim of this study was to investigate the possible somatotopy of the motor cortex on MCS-induced antinociception and the pattern of neuronal activation evaluated by Fos and Egr-1 immunolabel in an attempt to better understand the relation between MC and analgesia. Rats received epidural electrode implants placed over the MC, in three distinct areas (forelimb, hindlimb or tail), according to a functional mapping established in previous studies. Nociceptive threshold was evaluated under 15-min electrical stimulating sessions. MCS induced selective antinociception in the limb related to the stimulated cortex, with no changes in other evaluated areas. MCS decreased Fos immunoreactivity (Fos-IR) in the superficial layers of the dorsal horn of the spinal cord for all evaluated groups and increased Fos-IR in the PAG, although no changes were observed in the PAG for the tail group. Egr-1 results were similar to those obtained for Fos. Data shown herein demonstrate that MCS elicits a substantial and selective antinociceptive effect, which is mediated, at least in part, by the activation of descendent inhibitory pain pathway.

Blockade of peripheral and spinal Na+/H+ exchanger increases formalin-induced long-lasting mechanical allodynia and hyperalgesia in rats.

The Na(+)/H(+) exchanger (NHE) is involved in the regulation of intracellular pH and volume by mediating the electroneutral transport of H(+) against an influx of Na(+) ions. Since NHE1 regulates pH in neurons and astrocytes and it is expressed in nociceptive nerve fibers, it is likely that NHE may modulate neuronal excitability and pain transmission. The purpose of this study was to assess the participation of peripheral and spinal NHE in the secondary allodynia/hyperalgesia induced by formalin. In addition, we determined whether formalin injection modifies the expression of NHE1 in lumbar dorsal root ganglia (DRG) and dorsal spinal cord. Subcutaneous injection of 0.5% formalin into the dorsal surface of the hind paw produced acute nociceptive behaviors (flinching and licking/lifting) followed by long-lasting bilateral secondary mechanical allodynia/hyperalgesia. Peripheral and intrathecal pre-treatment (-10min) with selective NHE inhibitors 5-(N,N-dimethyl)amiloride hydrochloride (DMA, 0.3-30µM), 5-(N-ethyl-N-isopropyl)amiloride (EIPA, 0.3-30µM) and [1-(quinolin-5-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl] guanidine dihydrochloride (zoniporide, 0.03-3µM) significantly increased 0.5% formalin-induced bilateral long-lasting secondary allodynia/hyperalgesia. Contrariwise, local peripheral or intrathecal post-treatment (day 6 postinjection) with these NHE inhibitors did not affect formalin-induced nociceptive behaviors. Formalin injection reduced NHE1 expression in ipsilateral and contralateral spinal dorsal horns from day 1 to 12. In addition, formalin diminished NHE1 protein expression in DRG at day 12. These results suggest that NHE1 plays a role in pain processing at peripheral and spinal levels in formalin-induced long-lasting nociceptive behaviors. Additionally, these results suggest that proteins involved in pH regulation could be targets for the development of new analgesic drugs.

Effects of Se-phenyl thiazolidine-4-carboselenoate on mechanical and thermal hyperalgesia in brachial plexus avulsion in mice: mediation by cannabinoid CB1 and CB2 receptors.

In this study, we investigated the therapeutic effects of treatment with (R)-Se-phenyl thiazolidine-4-carboselenoate (Se-PTC), an organic selenium compound with antinociceptive properties, against mechanical and thermal hyperalgesia induced by brachial plexus avulsion (BPA), a neuropathic model in mice. The involvement of cannabinoid CB(1) and CB(2) receptors in the Se-PTC anti-hyperalgesic effect was also investigated. Se-PTC treatment at (25 and 50mg/kg, per oral, p.o.) lowered (BPA model) induced mechanical and thermal hyperalgesia in mice. Pretreatment with cannabinoid CB(1) (AM251; 1mg/kg, intraperitoneally, i.p.), or CB(2) (AM630; 3mg/kg, i.p.) receptor antagonists reverted the mechanical and thermal anti-hyperalgesic effect of Se-PTC (25mg/kg) in the BPA model. Selective CB(1) (ACEA, 10mg/kg, i.p.) and CB(2) (JWH-133, 10mg/kg, i.p.) receptor agonists lowered mechanical and thermal hyperalgesia in the BPA model, and this effect was prevented by selective CB(1) and CB(2) receptor antagonists. Gabapentin (70mg/kg, p.o.), positive control administration also lowered mechanical and thermal hyperalgesia in the BPA model. The results suggest that the mechanical and thermal hyperalgesia observed following BPA in mice is dependent on cannabinoid receptors. The results indicate that modulating cannabinoid receptors represent a valuable approach for the treatment of neuropathic pain. In conclusion, the results suggested that Se-PTC produces pronounced mechanical and thermal anti-hyperalgesic effects in neuropathic models in mice by modulating CB(1) and CB(2) receptors.

Effects of repeated stress on distal airway inflammation, remodeling and mechanics in an animal model of chronic airway inflammation.

BACKGROUND/AIMS: Epidemiological studies suggest that stress has an impact on asthmatic exacerbations. We evaluated if repeated stress, induced by forced swimming, modulates lung mechanics, distal airway inflammation and extracellular matrix remodeling in guinea pigs with chronic allergic inflammation. METHODS: Guinea pigs were submitted to 7 ovalbumin or saline aerosols (1-5 mg/ml during 4 weeks; OVA and SAL groups). Twenty-four hours after the 4th inhalation, guinea pigs were submitted to the stress protocol 5 times a week during 2 weeks (SAL-S and OVA-S groups). Seventy-two hours after the 7th inhalation, guinea pigs were anesthetized and mechanically ventilated. Resistance and elastance of the respiratory system were obtained at baseline and after ovalbumin challenge. Lungs were removed, and inflammatory and extracellular matrix remodeling of distal airways was assessed by morphometry. Adrenals were removed and weighed. RESULTS: The relative adrenal weight was greater in stressed guinea pigs compared to non-stressed animals (p < 0.001). Repeated stress increased the percent elastance of the respiratory system after antigen challenge and eosinophils and lymphocytes in the OVA-S compared to the OVA group (p < 0.001, p = 0.003 and p < 0.001). Neither collagen nor elastic fiber contents were modified by stress in sensitized animals. CONCLUSIONS: In this animal model, repeated stress amplified bronchoconstriction and inflammatory response in distal airways without interfering with extracellular matrix remodeling.

The involvement of the transient receptor potential A1 (TRPA1) in the maintenance of mechanical and cold hyperalgesia in persistent inflammation.

This study investigated the role of TRPA1 in the development and maintenance of mechanical and cold hyperalgesia in persistent inflammation induced by Complete Freund's Adjuvant (CFA) in mice. The intraplantar (i.pl.) injection of CFA induced a long lasting (28 days) hyperalgesia for both mechanical and thermal (cold) stimuli. The intraperitoneal (i.p., 30-300 mg/kg), intraplantar (i.pl., 100 microg/site) or intrathecal (i.t., 10 microg/site) injection of the TRPA1 selective antagonist HC-030031 significantly reduced the mechanical hyperalgesia evaluated by the von Frey hair test. The effect of HC-030031 was evidenced on the day after CFA injection and was kept throughout the test. However, the intracerebroventricular (i.c.v., 10 microg/site) injection of HC-030031 did not interfere with CFA-induced hyperalgesia. Treatment with HC-030031 (300 mg/kg, i.p.) completely inhibited the noxious cold hyperalgesia induced by tetrafluoroethane in mice that received CFA. The pre-treatment with the TRPA1 oligonucleotide antisense (AS-ODN, i.t.) consistently prevented both mechanical and cold hyperalgesia. Interestingly, both TRPA1 protein expression and mRNA were over-expressed in spinal cord and dorsal root ganglia (DRG) of mice treated with CFA, an effect that was fully prevented by the pre-treatment with the TRPA1 antagonist HC-030031. Collectively, the present results showed that TRPA1 present at either peripheral or spinal sites play a relevant role in the development and maintenance of both mechanical and cold hyperalgesia during CFA-induced inflammation. Thus, TRPA1 selective antagonists represent promising candidates to treat hyperalgesia in persistent inflammatory states.

Potentiation of local anesthetic activity of neosaxitoxin with bupivacaine or epinephrine: development of a long-acting pain blocker.

Local anesthetics effectively block and relieve pain, but with a relatively short duration of action, limiting its analgesic effectiveness. Therefore, a long-acting local anesthetic would improve the management of pain, but no such agent is yet available for clinical use. The aim of this study is to evaluate the potentiation of the anesthetic effect of neosaxitoxin, with bupivacaine or epinephrine in a randomized double-blind clinical trial. Ten healthy males were subcutaneously injected into the left and right forearms with a randomized pair of the following treatments: (i) bupivacaine (5 mg); (ii) neosaxitoxin (10 microg); (iii) neosaxitoxin (10 microg) plus bupivacaine (5 mg), and (iv) neosaxitoxin (10 microg) plus epinephrine (1:100.000), but all participant received all four formulations (in 2 ml; s.c.), with 1 month elapsing between the two round of experiments. A validated sensory and pain paradigm was used for evaluating the effect of the treatment 0-72 h after the injections, measuring sensory, pain, and mechanical touch perception threshold. The duration of the effect produced by combined treatments was longer than that by the single drugs. In conclusion, bupivacaine and epinephrine potentiate the local anesthetic effect of neosaxitoxin in humans when co-injected subcutaneously. The present results support the idea that neosaxitoxin is a new long-acting local pain blocker, with highly potential clinical use.

Pain and tactile stimuli during arterial puncture in preterm neonates.

The purpose of this study was to assess the behavioral and physiological reactivity of preterm neonates during different phases of a blood collection procedure involving arterial puncture. The sample consisted of 43 preterm and very low birth weight neonates with a postnatal age of 1 to 21 days who were hospitalized in the Neonatal Intensive Care Unit. The neonates were evaluated during the whole blood collection procedure. The assessment was divided into five consecutive phases: Baseline (BL); Antisepsis (A), covering the period of handling of the neonate for antisepsis prior to puncture; Puncture (P); Recovery-Dressing (RD), covering the period of handling of the neonate for dressing until positioning for rest in the isolette; and Recovery-Resting (RR). Facial activity was videotaped and analyzed using the Neonatal Facial Coding System (NFCS). The sleep-wake state and heart rate were registered at the bedside. There was a significant increase in NFCS score and heart rate, and more active behavior during phases A, P, and RD relative to BL. Regarding the tactile stimulation of the infant in pre-puncture (A) and post-puncture (RD), it was observed increased NFCS score, heart rate, and active behavior in comparison to the BL and RR phases. There was evidence of distress responses immediately before and after a painful event, quite apart from the pain reaction to the puncture procedure.

[Urticaria and angioedema]. / Urticaria y angioedema.

Urticaria is considered a heterogeneous group of diseases that share different patterns of skin reactions. The wide diversity in urticaria subtypes have been identified and this reflects partial understanding of the causes or factors that trigger it, as well as the molecular and cellular mechanisms that are involved in their physiopathology. The objective of this article was to make an extensive review of the literature to be able to offer the readers a complete information and updating on the basic, ethiologic and physiophatologic mechanisms and mainly to make a special emphasis on diagnosis and treatment of urticaria, promoting the continuous medical education.

[Unilateral keratoconus associated with continual eye rubbing due to nasolacrimal obstruction--case report]. / Ceratocone unilateral associado a constante massagem ocular devido à obstrução da via lacrimal--relato de caso.

To describe a possible case of unilateral keratoconus in a patient with continual eye rubbing due to an ipsilateral nasolacrimal obstruction in a 17-year-old woman complaint of progressing low visual acuity in the left eye. Presented with constant epiphora in the left eye throughout her life as a result of ipsilateral nasolacrimal obstruction, which required frequent wiping of this eye. Based on ocular examination, the patient was diagnosed as having unilateral keratoconus in the left eye. As in other studies, keratoconus is thought to be associated with persistent eye rubbing. This patient represents a case of unilateral keratoconus, where there is a confirmed history of habitual eye rubbing due to ipsilateral nasolacrimal obstruction, thereby suggesting a possible causal relationship between eye rubbing and keratoconus.

[Transcranial magnetic stimulation: review of accidental seizures]. / Estimulação Magnética Transcraniana: revisão dos casos de convulsões acidentais.

Transcranial magnetic stimulation (TMS) is a new technique that has been used for the treatment of neuropsychiatric disorders, specially depression. It uses a magnetic stimulator that generates a magnetic field that is applied over the patient's skull with a coil. Possible seizures may be induced accidentally by TMS. TMS is usually used with sub threshold stimuli and seizures may occur by chance, especially when over the safety parameters. This article reviews the eight cases of undesirable seizures occurred with rTMS The possible mechanisms of seizure induction and the patients profile with a higher risk of convulsion are also described.