Visão integrativa da dor em seu aspecto biopsicossocial / Integrative view of pain in its biopsychosocial aspect / Visión integradora del dolor en su vertiente biopsicosocial

Na definição padrão da medicina a nocicepção ou algesia é a transdução, condução e processamento de sinais nervosos aferentes gerados por nociceptores estimulados,resultando na percepção da dor. Os sinais de estímulos nocivos (mecânicos, térmicos ou químicos) são transmitidos principalmente através de dois tipos de nervos. As terminações nervosas das pequenas fibras mielinizadas a delta e as fibras C não mielinizadas estão localizadas na pele, tecido subcutâneo, periósteo, articulações, músculos e vísceras. As fibras beta mielinizadas, as maiores, normalmente transmitem estímulos não nocivos, como toque, vibração, pressão, movimento e propriocepção. No entanto, a entrada não nociva dessas fibras pode ser incorretamente processada em um sistema nervoso central alterado, resultando na percepção da dor (alodinia).

‘Sirim’ (Cold) Pain as a Common Symptom in Korean Patients with Clinically Suspected Small-Fiber Neuropathy

BACKGROUND AND PURPOSE: Diagnosing small-fiber neuropathy (SFN) is challenging because there is no gold-standard test and few diagnostic tests. This study investigated the clinical symptom profile and its associations with the results of quantitative sensory testing (QST) and the quantitative sudomotor axon reflex test (QSART) as well as the quality of life (QOL) in patients with clinically suspected SFN. METHODS: This study involved 63 patients with clinically suspected length-dependent SFN. Assessments were performed using QST, QSART, SFN Symptoms Inventory Questionnaire, Neuropathic Pain Symptom Inventory, ‘Sirim’ frequency and ‘Sirim’ (cold) pain severity, and 36-item Short-Form Health Survey. Multiple logistic and linear regression analyses were performed to predict risk factors for QST or QSART abnormalities and QOL, respectively. RESULTS: ‘Sirim’ and ‘Sirim’ pain was the most-common (84%) and the most-severe complaint (mean score of 6.3 on a numerical rating scale ranging from 0 to 10) in patients with clinically suspected SFN. The findings of QST [cold detection threshold (CDT)] and QSART were abnormal in 71% (n=45/57) and 62% (n=39/56) of the patients, respectively. An abnormal CDT was correlated with more-severe stabbing pain (odds ratio=2.23, 95% CI=1.02–4.87, p=0.045). Restless-leg symptoms (β=−7.077) and pressure-evoked pain (β=−5.034) were independent predictors of the physical aspects of QOL. CONCLUSIONS: ‘Sirim’ pain, similar to cold pain, should be considered a major neuropathic pain in SFN. Among pain characteristics, stabbing pain of a spontaneous paroxysmal nature may be more pronounced in the setting of dysfunctional Aδ fibers with functional autonomic C fibers.

Definition and diagnosis of small fiber neuropathy: consensus from the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology / Definição e diagnóstico de neuropatia de fibras finas: consenso do Departamento Científico de Neuropatias Periféricas da Academia Brasileira de Neurologia

ABSTRACT The aim of this study was to describe the results of a Brazilian Consensus on Small Fiber Neuropathy (SFN). Fifteen neurologists (members of the Brazilian Academy of Neurology) reviewed a preliminary draft. Eleven panelists got together in the city of Fortaleza to discuss and finish the text for the manuscript submission. Small fiber neuropathy can be defined as a subtype of neuropathy characterized by selective involvement of unmyelinated or thinly myelinated sensory fibers. Its clinical picture includes both negative and positive manifestations: sensory (pain/dysesthesias/pruritus) or combined sensory and autonomic complaints, associated with an almost entirely normal neurological examination. Standard electromyography is normal. A growing list of medical conditions is associated with SFN. The classification of SFN may also serve as a useful terminology to uncover minor discrepancies in the normal values from different neurophysiology laboratories. Several techniques may disclose sensory and/or autonomic impairment. Further studies are necessary to refine these techniques and develop specific therapies.

RESUMO O objetivo deste estudo é descrever os resultados de um Consenso Brasileiro sobre Neuropatia de Fibras Finas (NFF). Quinze neurologistas (membros da Academia Brasileira de Neurologia) revisaram uma versão preliminar do artigo. Onze panelistas se reuniram na cidade de Fortaleza para discutir e terminar o texto para a submissão do manuscrito. NFF pode ser definida como um subtipo de neuropatia caracterizada pelo envolvimento seletivo de fibras sensitivas amielínicas ou pouco mielinizadas. Seu quadro clínico inclui manifestações negativas e positivas: sensitivas (dor/disestesias/prurido) ou queixas sensitivas e autonômicas combinadas, associadas a exame neurológico quase totalmente normal. A eletromiografia convencional é normal. Uma lista crescente de condições médicas causa NFF. NFF também pode servir como uma terminologia útil para referenciar pequenas discrepâncias nos valores normais de diferentes laboratórios de neurofisiologia. Diferentes técnicas podem evidenciar anormalidades sensitivas e/ou autonômicas. São necessários mais estudos para refiná-las e para o desenvolvimento de terapias específicas.

Effects of High Concentrations of Naftopidil on Dorsal Root-Evoked Excitatory Synaptic Transmissions in Substantia Gelatinosa Neurons In Vitro / 대한배뇨장애요실금학회지

PURPOSE: Naftopidil ((±)-1-[4-(2-methoxyphenyl) piperazinyl]-3-(1-naphthyloxy) propan-2-ol) is prescribed in several Asian countries for lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Previous animal experiments showed that intrathecal injection of naftopidil abolished rhythmic bladder contraction in vivo. Naftopidil facilitated spontaneous inhibitory postsynaptic currents in substantia gelatinosa (SG) neurons in spinal cord slices. These results suggest that naftopidil may suppress the micturition reflex at the spinal cord level. However, the effect of naftopidil on evoked excitatory postsynaptic currents (EPSCs) in SG neurons remains to be elucidated. METHODS: Male Sprague-Dawley rats at 6 to 8 weeks old were used. Whole-cell patch-clamp recordings were made using SG neurons in spinal cord slices isolated from adult rats. Evoked EPSCs were analyzed in Aδ or C fibers. Naftopidil or prazosin, an α1-adrenoceptor blocker, was perfused at 100 μM or 10 μM, respectively. RESULTS: Bath-applied 100 μM naftopidil significantly decreased the peak amplitudes of Aδ and C fiber-evoked EPSCs to 72.0%±7.1% (n=15) and 70.0%±5.5% (n=20), respectively, in a reversible and reproducible manner. Bath application of 10μM prazosin did not inhibit Aδ or C fiber-evoked EPSCs. CONCLUSIONS: The present study suggests that a high concentration of naftopidil reduces the amplitude of evoked EPSCs via a mechanism that apparently does not involve α1-adrenoceptors. Inhibition of evoked EPSCs may also contribute to suppression of the micturition reflex, together with nociceptive stimulation.

The effect of µ-opioid receptor activation on GABAergic neurons in the spinal dorsal horn

The superficial dorsal horn of the spinal cord plays an important role in pain transmission and opioid activity. Several studies have demonstrated that opioids modulate pain transmission, and the activation of µ-opioid receptors (MORs) by opioids contributes to analgesic effects in the spinal cord. However, the effect of the activation of MORs on GABAergic interneurons and the contribution to the analgesic effect are much less clear. In this study, using transgenic mice, which allow the identification of GABAergic interneurons, we investigated how the activation of MORs affects the excitability of GABAergic interneurons and synaptic transmission between primary nociceptive afferent and GABAergic interneurons. We found that a selective µ-opioid agonist, [D-Ala², NMe-Phe⁴, Gly-ol]-enkephanlin (DAMGO), induced an outward current mediated by K⁺ channels in GABAergic interneurons. In addition, DAMGO reduced the amplitude of evoked excitatory postsynaptic currents (EPSCs) of GABAergic interneurons which receive monosynaptic inputs from primary nociceptive C fibers. Taken together, we found that DAMGO reduced the excitability of GABAergic interneurons and synaptic transmission between primary nociceptive C fibers and GABAergic interneurons. These results suggest one possibility that suppression of GABAergic interneurons by DMAGO may reduce the inhibition on secondary GABAergic interneurons, which increase the inhibition of the secondary GABAergic interneurons to excitatory neurons in the spinal dorsal horn. In this circumstance, the sum of excitation of the entire spinal network will control the pain transmission.

A histomorphometric study of unmyelinated fibers of the fibular nerve in Wistar rats / Histomorfometria das fibras amielínicas do nervo fibular em ratos Wistar

ABSTRACT There are few histomorphometric studies on the unmyelinated fibers of the fibular nerve in rats, and the number of experimental studies using this nerve has been increasing in the last years. Sixty-two percent of the endoneurial area from 10 fibular nerves of adult Wistar rats was scanned by electron microscopy, and digitized. The total number of unmyelinated axons (1.882 ± 271) was significantly lesser, and their axon diameters (0.2 µm to 2.8 µm) significantly higher than that determined in previous studies. The histogram peaked at 1 µm. The differences could be due to the nerve sampled area, the number and the age of the animals evaluated, and the laboratory techniques used. This study brings new and referential data to be used in experimental investigations involving histomorphometric evaluation of the rat fibular nerve.

RESUMO Embora o nervo fibular de ratos venha sendo incluído progressivamente em maior número de estudos experimentais nos últimos anos, há poucos estudos a respeito das suas fibras amielínicas. Os nervos fibulares de 10 ratos Wistar adultos foram avaliados através de microscopia óptica e eletrônica. Varredura sistemática através de microscopia eletrônica de transmissão das áreas fasciculares da porção distal no nervo foi realizada. Em média, 62% da área endoneural foi digitalizada. O número total de axônios amielínicos encontrados (1.882 ± 271) foi significativamente menor e as medidas dos diâmetros axonais (0,2 µm a 2,8 µm) maiores do que o determinado em estudos prévios. O pico do histograma foi constituído por fibras de 1µm. As diferenças podem ser devidas à amostragem de maior área endoneural, ao número e à idade dos animais avaliados, e as técnicas laboratoriais utilizadas. Os dados obtidos podem ser considerados referenciais para o nervo fibular de ratos Wistar adultos.

Efeito da toxina botulínica tipo A sobre a expressão de neuropeptídeos e o transporte mucociliar nasal em coelhos / Effect of botulinum toxin type A on nasal neuropeptides and mucociliary clearance in rabbits

INTRODUÇÃO: A toxina botulínica tipo A (TXB-A) tem sido testada no tratamento da rinite, principalmente nos casos de rinite idiopática. Sugere-se que um estado de hiper-reatividade do nervo trigêmeo esteja envolvido na fisiopatologia da rinite idiopática. O nervo trigêmeo possui fibras sensitivas não mielinizadas tipo C (FSNMT-C) que contém os neuropeptídeos substância P (SP) e peptídeo relacionado ao gene da calcitonina (CGRP). O óxido nítrico (NO) produzido pelas enzimas óxido nítrico sintase (NOS) também está envolvido nesse processo de neurorregulação nasal. O transporte mucociliar, mecanismo primário de defesa do sistema respiratório, é formado pelo batimento ciliar e muco nasal, e esses componentes podem ser influenciados por diferentes neuropeptídeos e neurotransmissores presentes na mucosa nasal. OBJETIVO: O objetivo deste estudo foi avaliar o efeito da TXB-A sobre a expressão da SP, CGRP e óxido nítrico sintase neural (nNOS), além de sua influência sobre o transporte mucociliar nasal em coelhos. MÉTODOS: Coelhos machos saudáveis da linhagem Nova Zelândia foram divididos em dois grupos: o grupo tratamento recebeu TXB-A (25UI) na concha nasomaxilar (CNM) do lado direito e soro fisiológico a 0,9% (SF0,9%) na CNM esquerda. O grupo controle recebeu SF0,9% na CNM direita e nenhuma intervenção na CNM esquerda. Foram investigados os efeitos da TXB-A sobre a expressão da SP, CGRP e nNOS no tecido de CNM por meio da imuno-histoquímica. Para esta análise, dividiu-se o tecido em camada externa (CE, acima da membrana basal) e camada interna (CI, abaixo da membrana basal). Avaliou-se também a presença de apoptose celular, a frequência de batimento ciliar (FBC), o perfil histoquímico do muco nasal (glicoproteínas ácidas e neutras) e a espessura do epitélio (ESP-CE). RESULTADOS: Foi observado um aumento significativo na quantidade de células apoptóticas na CNM do grupo tratamento que recebeu TXB-A em comparação aos controles (p <= 0,001). A CNM do grupo tratamento...(au)

INTRODUCTION: Botulinum toxin type A (BoNT-A) has been assessed in the treatment of rhinitis, especially in cases of idiopathic rhinitis. Trigeminal hyper-responsiveness appears to be involved in the pathological process of idiopathic rhinitis. Trigeminal nociceptive type C unmyelinated sensory fibers contain the neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP). Nitric oxide (NO) produced by the enzyme nitric oxide synthase (NOS) are also involved in this nasal neurorregulation process. The mucociliary clearance, primary defense system of the respiratory system, is composed by the ciliary beat and nasal mucus. These components can be influenced by different nasal neuropeptides and neurotransmitters. OBJECTIVE: The aim of this study was to evaluate the effect of BoNT-A on the expression of SP, CGRP and neural nitric oxide synthase (nNOS), and its influence on nasal mucociliary clearance in rabbits. METHODS: Healthy New Zealand male rabbits were divided into two groups: the treatment group was challenged with BoNT-A (25UI) in the right nasomaxillary turbinate (NMT) and saline (SF0.9%) in the left NMT. The control group received SF0.9% in the right NMT and no-intervention in the left NMT. We investigated the effects of BoNT-A on SP, CGRP and nNOS expression in the NMT tissue by immunohistochemistry. Each area of interest was subdivided into an internal layer (IL: below the basement membrane) and outer layer (OL: above the basement membrane) for analysis. It was also assessed signs of cellular apoptosis, ciliary beat frequency (CBF), mucus histochemical profile (acidic and neutral glycoproteins) and epithelial thickness (EP-TH). RESULTS: It was observed a significant increase in the amount of apoptotic cells in the BoNT-A-challanged NMT compared with controls (p <= 0.001). The NMT of treatment group which received only SF0.9% showed an increase in the amount of apoptotic cells in the IL compared with controls (NMT SF0.9%, p = 0.035)...

Neuropatía diabética periférica: eficacia clínica de la evaluación semiológica / Diabetic peripheral neuropathy: semiológica clinical efficacy of assessment

El diagnóstico de la Neuropatía Diabética Periférica es tardío. Identificar maniobras semiológicas que permitan el diagnóstico precoz de la neuropatía diabética. Estudio de casos, analítico, transversal y operacional: personas sanas, prediabéticos, diabéticos de reciente diagnóstico y diabéticos de más de 5 años de diagnóstico. Se realizaron 2 evaluaciones: la primera por dos investigadores a ciegas que evaluaron: sensibilidad mecánica, reflejos osteotendinosos y palestesia. También se evaluación de la córnea con Rosa de Bengala y se aplicó el Cuestionario DN4. Segunda Evaluación: von Frey. Biopsia de Piel: será tratada con inmunohistoquímica de campo claro. Muestra de 25 personas. El DN4, obtuvo 14 personas con dolor neuropático. La tinción con Rosa de Bengala obtuvo 7 pacientes con ojo seco y una diabética con más de 5 años de diagnóstico con alteración corneal. En la evaluación con von Frey hubo 3 pacientes con zonas sin respuesta al microfilamento de 10 g. La inmunohistoquímica demostró que el número y densidad de fibras nerviosas tuvo un promedio de 7 fibras/campo en sanos y a partir de los prediabéticos disminuyó desde 4,4 fibras/campo. El ojo seco justifica la evaluación periódica del internista. La evaluación de la sensibilidad con los filamentos de von Frey señala que el monofilamento utilizado individualmente tiene menor eficiencia diagnóstica. La biopsia demostró una capacidad diagnóstica precoz de esta, aún en ausencia de síntomas. La biopsia de piel con cuantificación del número y densidad de fibras, es útil en la identificación temprana de lesión de fibras C y se comporta como método de pesquisa.

The diagnosis of Diabetic Peripheral Neuropathy is made lately. To identify semiological maneuvres that allow early diagnosis of diabetic neuropathy. Case studie, analitic, transversal and operational, without therapeutic intervention in healthy, prediabetic, diabetic and newly diagnosed diabetes over 5 years of diagnosis. The First Assessment was: conducted by two blinded researchers measuring mechanical sensitivity, tendon reflexes, and palesthesia. Von Frey 3) Skin biopsy: the cornea Bengal Rose and DN4 Questionnaire. The second assessment was done with brightfield immunohistochemistry. The sample consisted of 25 persons. The DN4 had 14 people with neuropathic pain. Staining with Rose Bengal scored 7 persons. The second Assessment was done in patients with dry eye and over 5 years of diagnosis of corneal disorder. The evaluation with von Frey 3 patients with no response areas were obtained at 10 g microfilament. Immunohistochemistry showed that the number and density of nerve fibers had an average of 7 fibers in healthy and from prediabetic decreased to 4.4 fibers. The Dry eye justifies the periodic evaluation by the internist. The evaluation of sensitivity with von Frey hairs used indicate that the monofilament has a lower diagnostic efficiency individually. The biopsy revealed an early diagnostic capacity in this condition in the absence of symptoms. Skin biopsy with quantification of the number and density of nerve fibers is useful in early identification of C fiber damage and behaves like screening method.

Understanding itch: An update on mediators and mechanisms of pruritus.

Pruritus is the most common symptom secondary to skin diseases. Advances in the fi elds of neurobiology, immunology and physiology have made it possible for us to understand and unravel the deeper pathophysiological basis of pruritus. This review aims to update our current understanding of the mechanisms and mediators of pruritus. Special attention is paid to endogenous itch mediators particularly newly identifi ed ones like endovanilloids, opioids, neurotrophins, cannabinoids, proteases and cytokines. Various theories explaining the peripheral encoding of itch are reviewed. Multiple neural pathways including the central itch pathways as well as supraspinal processing of itch and brain areas involved in pruritus are highlighted. Apart from peripheral itch mediators, spinal neural receptors are also involved in control of itch and should form part of the development of a novel antipruritic strategy. Further studies are required to fi ll the lacunae in our current understanding of the pathophysiology of pruritus.

El abordaje homeopático de la tos / The homeopathic approach cough

El organismo humano posee distintos mecanismos de defensa natural para sus diversos sistemas, los que son conocidos como signos clínicos o lo que Hahnemann llamaba en los §6 y 7 del Organon la expresión de la fuerza vital. La tos es un fenómeno producido por un mecanismo reflejo que emerge en los receptores vagales situados a lo largo del tracto respiratorio. Se han descrito tres tipos diferentes de receptores, los receptores de estiramiento de adaptación lenta (REAL), receptores de estiramiento de adaptación rápida (REAR) y las fibras C. Este reflejo tusígeno consiste en tres fases: inspiratoria, compresiva y espiratoria. Es importante tener muy en cuenta que la tos es tan sólo un síntoma de un cuadro clínico complejo e individual que se desarrolla en la totalidad del organismo. Incluso la medicina convencional reconoce que la tos, aunque puede ser un síntoma problemático, es una forma de curación del cuerpo; en este sentido, se debe hacer lo posible por no erradicarla, menos aún en menores de seis años, a través de antitusígenos de venta libre.

Human organism has different natural defense mechanisms for its various systems,these mechanisms are known as clinical signs or what Hahnemann called in § 6and 7 of Organon “expression of the vital force”. Cough is a phenomenon caused by a reflection mechanism emerges vagal receptors along the respiratory tract have been described three types of receptors, slowly adapting stretch receptors (SARs), rapidly adapting stretch receptors (RARs) and C-fibers. This cough reflex consists of three phases, the first “inspiratory”, “compression” and “expiratory”. It is important to bear in mind that the cough is just a symptom of a complex clinical picture and individual that develops in the whole organism, even conventional medicine recognizes that cough, but can be a troubling symptom, it is a form of healing the body, in this regard, it should be possible not eradicate it, even less in children under six years antitussives through counter.

Assessment of Diabetic Polyneuropathy and Autonomic Neuropathy Using Current Perception Threshold in Korean Patients with Diabetes Mellitus

BACKGROUND: The current perception threshold (CPT) could be quantified by stimulating Abeta and C fibers at 2,000 and 5 Hz, respectively. C fibers play a role in the autonomic nervous system and are involved in temperature and pain sensation. We evaluated the usefulness of CPT for diagnosing distal polyneuropathy (DPN) and cardiovascular autonomic neuropathy (CAN) in diabetic patients. METHODS: The CPT was measured in the index finger (C7 level) and in the third toe (L5 level) in diabetic patients aged 30 to 69 years. We assessed DPN according to the neuropathy total symptom score-6 (NTSS-6) and 10-g monofilament pressure sensation. Subjects with a NTSS-6 >6 or with abnormal 10-g monofilament sensation were defined to have DPN. CAN was evaluated by spectral analysis of heart rate variability and by Ewing's traditional tests. RESULTS: The subjects with DPN had significantly higher CPT at all of the frequencies than the subjects without DPN (P6 could be most precisely predicted by CPT at 2,000 and 5 Hz, respectively. However, only 6.5% and 19.6% of subjects with DPN had an abnormal CPT at 2,000 Hz at the C7 and L5 levels. Although CPT at 5 Hz showed a negative correlation with the power of low and high frequency in the spectral analysis (P<0.05), only 16.7% of subjects with CAN exhibited an abnormal CPT at the same frequency. CONCLUSION: Although the CPT is significantly associated with neuropathic symptoms or signs corresponding to the nerve fiber stimulated, it provides little additional information compared with conventional evaluations.

Chemotherapy induced peripheral neuropathic pain / 대한마취과학회지

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most serious complications associated with anticancer drugs. CIPN leads to a lower quality of life and dysfunction of the sensory, motor, and autonomic systems, and often causes patients to discontinue chemotherapy. It is usually misdiagnosed and undertreated due to a lack of consensus and unclear pathophysiology, for which many mechanisms have been suggested, including mitochondrial dysfunction, various pain mediators, abnormal spontaneous discharge in A and C fibers, and others. To date, no agents have been shown to effectively prevent CIPN, leading to debate as to the standard protocol. Duloxetine has demonstrated a moderate therapeutic effect against CIPN. Although tricyclic antidepressants (such as nortriptyline or desipramine), gabapentin, and a topical gel containing baclofen (10 mg), amitriptyline HCL (40 mg), and ketamine (20 mg) showed inconclusive results in CIPN trials, these agents are currently considered the best options for CIPN treatment. Therefore, further studies on the pathophysiology and treatment of CIPN are needed.

Reflejo C evocado en el músculo digástrico: un nuevo método para evaluar actividad wind-up trigeminal aplicable a principios activos de plantas medicinales / C-reflex evoked in the digastric muscle: a new method for evaluating trigeminal wind-up activity applicable to active principles of medicinal plants

Wind-up is a measure of nociceptive neurons synaptic potentiation and constitutes an important mechanism in the generation of central sensitization in chronic pain. At the spinal level, the C-evoked reflex in the bicep femoris muscle, by low frequency repetitive stimulation of the sural nerve, has enabled us to evaluate the wind-up of nociceptive neurons of the dorsal horn, and also the effect of antinociceptive drugs with a possible potential therapeutic value in chronic pain. In the present work, we electrophysiologically evaluated the trigeminal wind-up activity, utilizing as an experimental paradigm the evoked C-reflex in the Sprague-Dawley rat digastric muscle. The results obtained indicate that: (a) It is possible to evoke an electromyographic reflex in the digastric muscle by stimulation of C-fibers belonging to the third trigeminal branch; (b) It is possible to potentiate the trigeminal C-reflex with low frequency stimuli (wind-up) and (c) it is possible to depress the trigeminal wind-up with the μ-opioid agonist morphine and with the NMDA receptor antagonist, ketamine. We can conclude that the simple measurement of the trigeminal wind-up will facilitate future studies on the analgesic efficacy of new drugs in oro-facial chronic pain syndromes like migraine and with special emphasis on medicinal plant active principles.

El wind-up refleja la potenciación sináptica en neuronas nociceptivas y constituye un importante mecanismo en la generación de sensibilización central en dolor crónico. A nivel espinal, el reflejo C evocado en el músculo bicep femoris por estimulación repetitiva de baja frecuencia del nervio sural ha permitido evaluar la actividad wind-up en neuronas nociceptivas del cuerno dorsal, así como el efecto de drogas antinociceptivas con un posible potencial terapéutico en dolor crónico. En el presente trabajo evaluamos electrofisiológicamente la actividad wind-up trigeminal, utilizando como paradigma experimental el reflejo C evocado en el músculo digástrico de ratas Sprague-Dawley. Los resultados obtenidos indican que: (a) es posible evocar un reflejo electromiográfico en el músculo digástrico de la rata por estimulación de fibras C de la tercera rama del trigémino; (b) es posible potenciar el reflejo C trigeminal con estímulos de baja frecuencia (wind-up) y (c) es posible deprimir el wind-up trigeminal con el agonista μ-opioide morfina y con el antagonista NMDA, ketamina. Podemos concluir que la medición simple del wind-up trigeminal mediante el reflejo C evocado en el músculo digástrico facilitará futuros estudios sobre eficacia analgésica de nuevos fármacos en cuadros de dolor orofacial crónicos, como la migraña, con especial énfasis en los principios activos de plantas medicinales.

Demyelination of neurofilament protein 200 immune positive never fibers in human pulp

INTRODUCTION: Mammalian tooth pulp is densely innervated by sensory nerves that are mostly C fibers and A delta fibers. However, there is evidence suggesting that many unmyelinated axons in the pulp are in fact parent meylinated axons. MATERIALS AND METHODS: The pulp was removed from healthy premolars and 3rd molars extracted from juveniles and adults undergoing orthodontic treatment, and immunohistochemical staining were applied with NPF200 antibodies, which specifically dye myelinated axons. The specimens underwent an electron microscopy examination with diaminobenzidine (DAB) immunostaining after observation and analysis by fluorescence and confocal laser scanning microscopy. RESULTS: The NPF200 immuno-positive axons in the radicular pulp areas were observed as bundles of many nerve fibers. Many small bundles were formed with fewer axons when firing to the coronal pulp areas and then reachrd a different direction. CONCLUSION: Myelinated fibers innervated to the dental pulp maintain their myelins in the radicular portion, but these fibers lost myelins in the coronal portion. Afterthe loss of myelin, the size of the axoplasm also decreased.

Heat Acclimatization in Hot Summer for Ten Weeks Suppress the Sensitivity of Sweating in Response to Iontophoretically-administered Acetylcholine

To determine the peripheral mechanisms involved in thermal sweating during the hot summers in July before acclimatization and after acclimatization in September, we evaluated the sweating response of healthy subjects (n=10) to acetylcholine (ACh), a primary neurotransmitter involved in peripheral sudomotor sensitivity. The quantitative sudomotor axon reflex test (QSART) measures sympathetic C fiber function after iontophoresed ACh evokes a measurable reliable sweat response. The QSART, at 2 mA for 5 min with 10% ACh, was applied to determine the directly activated (DIR) and axon reflex-mediated (AXR) sweating responses during ACh iontophoresis. The AXR sweat onset-time by the axon reflex was 1.50+/-0.32 min and 1.84+/-0.46 min before acclimatization in July and after acclimatization in September, respectively (p<0.01). The sweat volume of the AXR(1) [during 5 min 10% iontophoresis] by the axon reflex was 1.45+/-0.53 mg/cm2 and 0.98+/-0.24 mg/cm2 before acclimatization in July and after acclimatization in September, respectively (p<0.001). The sweat volume of the AXR(2) [during 5 min post-iontophoresis] by the axon reflex was 2.06+/-0.24 mg/cm2 and 1.39+/-0.32 mg/cm2 before and after acclimatization in July and September, respectively (p<0.001). The sweat volume of the DIR was 5.88+/-1.33 mg/cm2 and 4.98+/-0.94 mg/cm2 before and after acclimatization in July and September, respectively (p<0.01). These findings suggest that lower peripheral sudomotor responses of the ACh receptors are indicative of a blunted sympathetic nerve response to ACh during exposure to hot summer weather conditions.

The mechanisms underlying long-term potentiation of C-fiber evoked field potentials in spinal dorsal horn / 生理学报

Long-term potentiation (LTP) of C-fiber evoked field potentials in spinal dorsal horn is first reported in 1995. Since then, the mechanisms underlying the long-lasting enhancement in synaptic transmission between primary afferent C-fibers and neurons in spinal dorsal horn have been investigated by different laboratories. In this article, the related data were summarized and discussed.

Decreased Hepatic Nerve Fiber Innervation in Patients with Liver Cirrhosis

BACKGROUND/AIMS: Hepatic nerve innervation plays important roles in hepatic metabolism and hemodynamic mechanisms. We compared the distribution patterns of hepatic nerves between normal livers and two liver diseases to elucidate the effects of liver disease on the distribution of hepatic nerves. METHODS: Tissue specimens were obtained by ultrasonography-guided needle biopsies from 10 normal controls, 74 patients with chronic hepatitis (CH), and 35 patients with liver cirrhosis (LC). The obtained specimens were immunohistochemically stained using antibodies for S-100 protein and alpha-smooth-muscle actin (alpha-SMA). The degree of the expression in liver tissues was quantified by manual counting of positively stained nerve fibers under light microscopy. The serum hyaluronic acid level was assayed in all subjects to evaluate hepatic fibrosis. Electron microscopy examinations were also performed. RESULTS: The hepatic nerve innervation was significantly lower in LC than in normal controls, as indicated by S-100 protein staining. alpha-SMA and hyaluronic acid levels were higher in LC and CH than in normal controls. Electron microscopy revealed that unmyelinated nerve fiber bundles in the intralobar connective tissue coursed in the vicinity of hepatic triads. CONCLUSIONS: These results suggest that hepatic nerve innervation can be decreased by hepatic inflammatory responses and/or fibrotic changes in LC patients. Further study is needed to clarify this observation.

Ultrastructure of the myelinated and unmyelinated nerve fibers of the tongue mucosa of albinus rat (Wistar) with aging / Ultraestructura de las Fibras Nerviosas Mielínicas y Amielínicas de la Mucosa Lingual de ratas Albinas (Wistar) Envejecidas

El objetivo de esta investigación fue estudiar las fibras sensitivas mielinizadas y amielínicas localizadas en la lámina propia subepitelial de la mucosa lingual de ratas. Se usó el método de impregnación argéntica, microscopía MET y mediciones morfométricas. Los resultados revelaron que los fascículos de fibras subepiteliales de las regiones anterior, media y posterior de la lengua provenían de su capa muscular profunda. Los grupos de fibras fueron localizados dentro del tejido conectivo de la lámina propia. Estas fibras nerviosas se ramificaron varias veces y en el tejido conectivo de las papilas formaron terminaciones simples o ramificados. Las papilas fungiformes y valadas contenían numerosas terminaciones nerviosas. La ultraestructura demostró en el axoplasma la presencia de neurofilamentos, mitocondrias y microtúbulos; aunque los registros morfométricos de las fibras mielinizadas mostraron que alrededor del 44 por ciento tenían un diámetro entre 3 y 4 µm, el valor promedio fue de 4.5 µm. El diámetro mayor fue de 12 µm y el menor de 1.4 um. Los rangos de menores diámetros fueron de 1 a 3 µm, siendo el promedio de 2.33 µm. En relación al espesor de las vainas de mielina, los valores obtenidos fueron de 0.2 a 0.8 um siendo el valor promedio de alrededor de 0,5 µm, en el 90 por ciento de ellas. En las fibras amielínicas los mayores diámetros (62 por ciento) variaron entre 0.25 y 0.75 µm. El valor promedio fue de 0.6 µm, siendo el valor máximo 3.17 µm y el mínimo 0.2 µm. El menor diámetro fue obtenido en 44 por ciento de las fibras amielínicas y los rangos variaron entre 0.2 y 0.4 µm. El valor máximo obtenido fue de 1 µm y el mínimo 0.12 µm.

The purpose of this paper was to study the sensory myelinated and unmyelinated nerve fibers found in the subepithelial lamina propria of tongue mucosa of aging rats. It was used the silver impregnation, transmission electron microscopy methods and morphometric measurements. The results revealed that subepithelial nerve fiber bundles of the anterior, medium and posterior regions of tongue were arise from deep muscular layer of tongue. The nerve fiber bundles were verified inside of the connective tissue of lamina propria. These nerve fibers branched several times and into the connective tissue papillae they form a single or ramified sensory nerve endings. The fungiform and vallate papillae contain numerous nerve terminals. The fine structure demonstrated that in the axoplasm were noted the presence of neurofilaments, mitochondria and microtubules. Although the morphometric data of myelinated fibers showed that about 44% having larger diameter between 3 to 4 µm and the mean value was 4.5 µm. The largest diameter was 12 µm and the smaller was 1.4 um. The smallest diameter ranges from 1 to 3 µm, being that the mean value was 2.33 µm. Concerning to the thickness of myelin sheets were revealed the values ranging from 0.2 to 0.8 µm being that the 90% present the values around 0.5 µm. The unmyelinated fibers showed the largest diameter (62%) varying from 0.25 to 0.75 µm. The mean value was 0.6 µm being the maximum value was 3.17 µm and the minimum was 0.2 µm. The smallest diameter was obtained in 44% of unmyelinated fibers which the diameter ranges from 0.2 to 0.4 µm.Then maximum value obtained was 1 µm and the minimum was 0.12 µm.

The Ultrastructure of TRPV1-positive Nerve Terminals in the Human Tooth Pulp / 대한해부학회지

The vanilloid receptor TRPV1 has been suggested to play an important role in thermal nociception and inflammatory hyperalgesia. In our previous study, we examined the expression of TRPV1 and colocalization of TRPV1 with substance P (SP) and calcitonin gene related peptide (CGRP) through fluorescence immunocytochemistry. Here, we investigated ultrastructural characteristics of TRPV1 immunoreactive fibers in the human tooth pulp through preembedding immunocytochemistry. TRPV1 immunoreactivity was present in the unmyelinated nerve fibers in the tooth pulp. There were two types of TRPV1 IR nerve fibers identified in the human tooth pulp: one containing clear round vesicles and many dense-cored vesicles, the other containing clear round vesicles and few dense-cored vesicles. TRPV1 immunoreactive fibers were constant in diameter without swellings along the length. Boutons en passant and boutons terminaux usually observed in the CNS were not observed in the TRPV1 immunoreactive fibers. Many vesicles were accumulated in the TRPV1 immunoreactive fibers, however synaptic structure was not found. It is known that dense-cored vesicles contain neuropeptides such as SP and CGRP and clear round vesicles contain neurotransmitter such as glutamate. Taken together, our results suggest that TRPV1 immunoreactive fibers showing distinct ultrastructructural features may be involved in inflammatory hyperalgesia and thermal nociception in the tooth pulp.

Interpretación fisiopatológica de los diferentes estadios de una pulpitis / Physiopathological interpretation of the different pulpitis stages

La caries dental que vulnera los tejidos duros del diente y compromete a la pulpa provoca un proceso inflamatorio que progresa por varias fases o estadios: pulpitis reversible, pulpitis transicional, pulpitis irreversible y pulpa necrótica. El tejido pulpar agredido por microorganismos no experimenta una necrosis repentina, sino que va sucumbiendo progresivamente, y cada uno de los estadios pulpares por los que transita el proceso, se puede ir identificando mediante el dolor con sus características semiológicas propias de cada fase, lo que permite precisar con bastante certeza el estado pulpar por el que avanza el proceso inflamatorio en dicho tejido. La interpretación fisiopatológica de los diferentes estadios pulpares por los que transita una pulpitis y el seguimiento del dolor como síntoma cardinal del proceso inflamatorio, es una forma de diagnóstico que complementa el pensamiento interpretativo del clínico que atiende estas urgencias, y le permite una mejor comprensión de su evolución y establecer así el correcto tratamiento(AU)

The dental caries that harms the hard tissues of the tooth and compromises the pulp produces an inflammatory process that progresses through various phases or stages: reversible pulpitis, transitional pulpitis, irreversible pulpitis and necrotic pulp. The pulpar tissue attacked by microorganisms does not experiment a sudden necrosis, but it progressively succumbs and each of the pulpar stages the process goes through may be identified by the pain with its own semiological characteristics of every stage, which allows to determine with enough accuracy the pulpar stage through which the inflammatory process advances in this tissue. The physiopathological interpretation of the different pulpar stages of a pulpitis and the follow-up of pain as a cardinal symptom of the inflammatory process is a form of diagnosis complementing the interpretative thinking of the clinician that gives attention to these emergencies. It also contributes to a better understanding of its evolution and to apply an adequate treatment(AU)