Situación actual de la prevención del cáncer de piel: una revisión sistemática / Current State of Skin Cancer Prevention: A Systematic Review

La mortalidad por cáncer de piel continúa aumentando a pesar de las numerosas intervenciones dedicadas a su prevención. El objetivo de esta revisión es estudiar la situación de la prevención primaria y secundaria del cáncer de piel en los últimos 10 años. Se incluyen un total de 63 revisiones, 30 (46,6%) revisiones incluyeron estrategias de prevención primaria y 35 (55,6%) de prevención secundaria, incorporando dos de las revisiones información sobre ambos tipos de estrategias. Para la prevención primaria, las medidas más estudiadas fueron los programas educativos (63,3%), seguidos de la creación de modelos para identificar a personas con alto riesgo de desarrollar un melanoma (17,6%) y la promoción del uso de fotoprotectores (11,8%). Los sistemas de toma de imagen para el diagnóstico precoz del cáncer de piel (40%), seguida por el empleo de smartphones y nuevas tecnologías (22,9%), así como el diagnóstico visual como cribado poblacional (17,4%), fueron las medidas de prevención secundaria más evaluadas. De todas las medidas revisadas, las estrategias de prevención primaria centradas en programas educativos para mejorar los hábitos de fotoprotección fueron las que resultaron más efectivas (AU)

Skin cancer deaths continue to rise despite the implementation of numerous preventive campaigns and programs. The aim of this systematic review was to evaluate reviews of primary and secondary skin cancer prevention strategies as reported over the past 10 years. We analyzed 63 systematic reviews and meta-analyses: 30 (46.6%) addressing primary interventions and 35 (55.6%) addressing secondary interventions. Two of the reviews covered both. The most widely reported primary prevention approaches were education programs (63.3%), followed by risk modeling to identify individuals at high risk for melanoma (17.6%), and the promotion of sunscreen use (11.8%). The most widely reported secondary prevention measures concerned imaging systems for early skin cancer detection (40%), smartphones and new technologies (22.9%), and visual diagnosis in population-based screening (17.4%). The most effective measures were primary prevention education programs to improve sun protection habits (AU)

[Translated article] Current State of Skin Cancer Prevention: A Systematic Review / Situación actual de la prevención del cáncer de piel: una revisión sistemática

Skin cancer deaths continue to rise despite the implementation of numerous preventive campaigns and programs. The aim of this systematic review was to evaluate reviews of primary and secondary skin cancer prevention strategies as reported over the past 10 years. We analyzed 63 systematic reviews and meta-analyses: 30 (46.6%) addressing primary interventions and 35 (55.6%) addressing secondary interventions. Two of the reviews covered both. The most widely reported primary prevention approaches were education programs (63.3%), followed by risk modeling to identify individuals at high risk for melanoma (17.6%), and the promotion of sunscreen use (11.8%). The most widely reported secondary prevention measures concerned imaging systems for early skin cancer detection (40%), smartphones and new technologies (22.9%), and visual diagnosis in population-based screening (17.4%). The most effective measures were primary prevention education programs to improve sun protection habits (AU)

La mortalidad por cáncer de piel continúa aumentando a pesar de las numerosas intervenciones dedicadas a su prevención. El objetivo de esta revisión es estudiar la situación de la prevención primaria y secundaria del cáncer de piel en los últimos 10 años. Se incluyen un total de 63 revisiones, 30 (46,6%) revisiones incluyeron estrategias de prevención primaria y 35 (55,6%) de prevención secundaria, incorporando dos de las revisiones información sobre ambos tipos de estrategias. Para la prevención primaria, las medidas más estudiadas fueron los programas educativos (63,3%), seguidos de la creación de modelos para identificar a personas con alto riesgo de desarrollar un melanoma (17,6%) y la promoción del uso de fotoprotectores (11,8%). Los sistemas de toma de imagen para el diagnóstico precoz del cáncer de piel (40%), seguida por el empleo de smartphones y nuevas tecnologías (22,9%), así como el diagnóstico visual como cribado poblacional (17,4%), fueron las medidas de prevención secundaria más evaluadas. De todas las medidas revisadas, las estrategias de prevención primaria centradas en programas educativos para mejorar los hábitos de fotoprotección fueron las que resultaron más efectivas (AU)

[Translated article] Environmental Impact of UV Filters / Impacto de los filtros ultravioleta en el entorno natural

UV filters are used daily by millions of people. Not all of these filters, however, are 100% biodegradable, and many wastewater treatments plants are ill-equipped to filter them properly. As a result, UV filters are increasingly reaching the environment. Various types have been detected in soil, continental water, oceans, and numerous organisms, including algae, corals, fish, mammals, and even land birds. In addition, some filters, benzophenone-3 and octocrylene in particular, are toxic to these organisms. Toxic effects include coral bleaching and interference with metabolic, enzymatic, and reproductive activities in practically all organisms. Preliminary data suggest that UV filters may be bioaccumulating in humans, as they have been detected in urine and breast milk. It should be noted, however, that research into the environmental impact of UV filters holds challenges and limitations (AU)

Los filtros ultravioleta (UV) se han convertido en compuestos de uso diario para millones de personas. Sin embargo, algunos de ellos no son biodegradables al 100% y las plantas de tratamiento de aguas residuales muchas veces no son capaces de filtrarlos correctamente. Todo ello está llevando a su diseminación ambiental y a la detección de distintos filtros UV en el suelo, las aguas continentales, los océanos y en múltiples organismos (algas, corales, peces, mamíferos, incluso aves terrestres). Además, algunos filtros UV, especialmente la benzofenona-3 y el octocrileno se han mostrado tóxicos en estos organismos. Entre sus efectos tóxicos destacamos el blanqueamiento de los corales y problemas metabólicos, enzimáticos y de capacidad reproductiva en prácticamente cualquier organismo. Existen datos preliminares sobre la posible bioacumulación de estos filtros UV en humanos, al detectarse en muestras de orina y leche materna. Sin embargo, el estudio del impacto medioambiental de los filtros UV presenta muchas limitaciones (AU)

Current State of Skin Cancer Prevention: A Systematic Review. / Situación actual de la prevención del cáncer de piel: una revisión sistemática.

Skin cancer deaths continue to rise despite the implementation of numerous preventive campaigns and programs. The aim of this systematic review was to evaluate reviews of primary and secondary skin cancer prevention strategies as reported over the past 10 years. We analyzed 63 systematic reviews and meta-analyses: 30 (46.6%) addressing primary interventions and 35 (55.6%) addressing secondary interventions. Two of the reviews covered both. The most widely reported primary prevention approaches were education programs (63.3%), followed by risk modeling to identify individuals at high risk for melanoma (17.6%), and the promotion of sunscreen use (11.8%). The most widely reported secondary prevention measures concerned imaging systems for early skin cancer detection (40%), smartphones and new technologies (22.9%), and visual diagnosis in population-based screening (17.4%). The most effective measures were primary prevention education programs to improve sun protection habits.

Liver transplant with controlled donors after circulatory death with normothermic regional perfusion and brain dead donors: A multicenter cohort study of transfusion, one-year graft survival and mortality.

BACKGROUND: Controlled donation after circulatory death (cDCD) has expanded the donor pool for liver transplantation (LT). However, transfusion requirements and perioperative outcomes should be elucidated. The aim of this multicenter study was to assess red blood cell (RBC) transfusions, one-year graft and patient survival after LT after cDCD with normothermic regional perfusion (NRP) compared with donors after brain death (DBD). METHODS: 591 LT carried out in ten centers during 2019 were reviewed. Thromboelastometry was used to manage coagulation and blood product transfusion in all centers. Normothermic regional perfusion was the standard technique for organ recovery. RESULTS: 447 patients received DBD and 144 cDCD with NRP. Baseline MCF Extem was lower in the cDCD group There were no differences in the percentage of patients (63% vs. 61% p = 0.69), nor in the number of RBC units transfused (4.7 (0.2) vs 5.5 (0.4) in DBD vs cDCD, p = 0.11. Twenty-six patients (6%) died during admission for LT in the DBD group compared with 3 patients (2%) in the cDCD group (p = 0.15). To overcome the bias due to a worse coagulation profile in cDCD recipients, matched samples were compared. No differences in baseline laboratory data, or in intraoperative use of RBC or one-year outcome data were observed between DBD and cDCD recipients. CONCLUSIONS: cDCD with NRP is not associated with increased RBC transfusion. No differences in graft and patient survival between cDCD and DBD were found. Donors after controlled circulatory death with NRP can increasingly be utilized with safety, improving the imbalance between organ donors and the ever-growing demand.

Experiencias del paciente durante la retirada de la ventilación mecánica invasiva: una revisión de la literatura / Patients’ experience during weaning of invasive mechanical ventilation: A review of the literature

Objetivo: La retirada de la ventilación mecánica invasiva (VMI) es un procedimiento en el que influyen factores fisiológicos y psicológicos, siendo estos últimos los menos estudiados. El objetivo fue identificar en la literatura, las experiencias de los pacientes durante la retirada de la VMI y cómo intervienen en dicho proceso. Método: Se realizó una búsqueda bibliográfica en las bases de datos Pubmed, CINAHL y PsycINFO. Los términos de búsqueda fueron: «patient», «experience» y «ventilator weaning». Los límites fueron la edad (> 19 años) y el idioma (inglés, español y finlandés). Resultados: Se analizaron 15 publicaciones. Los principales resultados se agruparon en tres grandes temas según las percepciones, sentimientos y experiencias del paciente, la influencia de la atención de los profesionales y los factores determinantes para la retirada exitosa de la VMI. Los pacientes recuerdan la retirada de la VMI como un proceso estresante y experimentan ansiedad, frustración, desesperación o incertidumbre. Las enfermeras tienen un papel fundamental en la mejora de la comunicación con el paciente y en la anticipación a sus necesidades. El soporte familiar y el cuidado proporcionado por los profesionales se destacan como fundamentales durante el proceso. Para conseguir una retirada exitosa de la VMI se identifica la importancia de la autodeterminación, la automotivación y la confianza de los pacientes. Conclusiones: La atención psicológica, además de la física y la tecnológica, es importante durante la retirada de la VMI para proporcionar un cuidado holístico. Son necesarios estudios de intervención para lograr mejorar la atención a los pacientes durante dicho proceso

Objective: Weaning from invasive mechanical ventilation (IMV) is influenced by physiological and psychological factors, the latter being the least studied. The aim was to identify, through the literature, patients’ experiences during weaning from IMV and report its influencing factors. Method: The literature search was conducted using the Pubmed, CINAHL and PsycINFO databases. The search terms were: ‘patient’, ‘experience’ and ‘ventilator weaning’. The research limits were: age (> 19 years) and language (English, Spanish and Finnish). Results: Fifteen publications were analysed. The main results were grouped into three main categories according to patient's perceptions, feelings and experiences, influence of professionals’ attention and determinants for successful weaning. Patients remember IMV weaning as a stressful process where they experience anxiety, frustration, despair or uncertainty. Nurses have a key role in improving communication with patients and foreseeing their needs. Family support and the care provided by the caregivers were shown as essential during the process. The patient's self-determination, self-motivation and confidence are identified as important factors to achieve successful IMV weaning. Conclusions: Psychological care, in addition to physical and technical care, is important at providing holistic care. Interventional studies are needed to improve the care during the weaning experience

Patients' experience during weaning of invasive mechanical ventilation: A review of the literature. / Experiencias del paciente durante la retirada de la ventilación mecánica invasiva: una revisión de la literatura.

OBJECTIVE: Weaning from invasive mechanical ventilation (IMV) is influenced by physiological and psychological factors, the latter being the least studied. The aim was to identify, through the literature, patients' experiences during weaning from IMV and report its influencing factors. METHOD: The literature search was conducted using the Pubmed, CINAHL and PsycINFO databases. The search terms were: "patient", "experience" and "ventilator weaning". The research limits were: age (>19years) and language (English, Spanish and Finnish). RESULTS: Fifteen publications were analysed. The main results were grouped into three main categories according to patient's perceptions, feelings and experiences, influence of professionals' attention and determinants for successful weaning. Patients remember IMV weaning as a stressful process where they experience anxiety, frustration, despair or uncertainty. Nurses have a key role in improving communication with patients and foreseeing their needs. Family support and the care provided by the caregivers were shown as essential during the process. The patient's self-determination, self-motivation and confidence are identified as important factors to achieve successful IMV weaning. CONCLUSIONS: Psychological care, in addition to physical and technical care, is important at providing holistic care. Interventional studies are needed to improve the care during the weaning experience.

Estudio de caso. Terapia del movimiento inducido por restricción en parálisis cerebral infantil / Case report. Constraint-induced movement therapy in childhood cerebral palsy

Introducción. El caso trata de una niña de 30 meses de edad diagnosticada de parálisis cerebral con hemiparesia espástica. La intervención desde atención temprana se fundamenta en la aplicación de un protocolo modificado de terapia del movimiento inducido en entornos naturales (hogar y colegio). Objetivos. El objetivo es mejorar el desempeño ocupacional e incrementar el uso voluntario de la mano parética en actividades bimanuales, basándose en la estimulación neurológica implícita en el aprendizaje motor. Resultados. Mejora del desempeño en actividades de la vida diaria. Se registraron ganancias a nivel emocional y actitudinal. AHA incrementa 7 puntos. PDMS-2 suma 2 puntos en visual motora y 2 puntos en edad equivalente. A nivel funcional se alcanzan ganancias en 8 de los 10 objetivos (Goal Attainment Scale). Los resultados obtenidos invitan a seguir investigando el potencial de esta herramienta en entornos naturales (AU)

Introduction. We report the case of a 30-month-old girl with unilateral spastic cerebral palsy (CP). Early Intervention was based on an eco-modified protocol of constraint-induced movement therapy (mCIMT). Objectives. The objectives were to improve occupational development and to increase spontaneous upper limb use during bimanual activities by means of neurological stimulation involved in the leaning of motor skills. Results. There was improvement in the development of activities of daily living, as well as emotional and attitudinal gains. An increment of 7 points was recorded in the assisting hand assessment (AHA). The Peabody developmental motor sclaes-2 (PDMS-2) increased 2 points in the visual motor (VM) subtest and another 2 points in equivalent age (EA). In functional goals, progress was achieved in 8 of the 10 objectives (Goal Attainment Scale). The results obtained encourage us to keep investigating the potential of this tool in natural environments (AU)

Blockade of nociceptive sensory afferent activity of the rat knee joint by the bradykinin B2 receptor antagonist fasitibant.

OBJECTIVE: The aim of this study was to determine in intact and inflamed knee joints of the rat, the effect of the bradykinin (BK) B2 receptor antagonist fasitibant (MEN16132) on nociceptor mechanosensitivity and hyperalgesia. METHODS: Joint afferent sensory fibers of the medial articular nerve of anesthetized animals were electrophysiologically recorded, measuring nerve impulse activity evoked by passive innocuous and noxious movements of the joint, in intact and kaolin and carrageenan-injected joints. Knee joints of rats were also acutely inflamed by intra-articular injection of carrageenan alone. Long term duration of fasitibant antinociceptive effects were behaviorally evaluated using the incapacitance test. RESULTS: BK (100 µM) injected into the saphenous artery, induced excitation and sensitization of multi- and single unit recordings. Fasitibant (300 µM) injected prior to BK, reduced its excitatory effects as well as the overall increase of movement-evoked activity resulting from repeated injections of BK. Fasitibant did not affect movement-evoked activity of sensory fibers of intact, non-inflamed knee joints. Intra-articular fasitibant (100 µg/knee) significantly reduced the carrageenan-induced inflammatory hyperalgesia measured with the incapacitance test up to four days after treatment. This antinociceptive effect was not obtained with systemic endovenous injection of the drug. CONCLUSIONS: Fasitibant prevents B2 receptor-mediated activation and sensitization of peripheral joint afferents and the ensuing inflammatory hyperalgesia, and may be a useful, novel drug for arthritis pain treatment.

Temperature modulation of slow and fast cortical rhythms.

In the local cortical network, spontaneous emergent activity self-organizes in rhythmic patterns. These rhythms include a slow one (<1 Hz), consisting in alternation of up and down states, and also faster rhythms (10-80 Hz) generated during up states. Varying the temperature in the bath between 26 and 41 degrees C resulted in a strong modulation of the emergent network activity. Up states became shorter for warmer temperatures and longer with cooling, whereas down states were shortest at physiological (36-37 degrees C) temperature. The firing rate during up states was robustly modulated by temperature, increasing with higher temperatures. The sparse firing rate during down states hardly varied with temperature, thus resulting in a progressive merging of up and down states for temperatures around 30 degrees C. Below 30 degrees C and down to 26 degrees C the firing lost rhythmicity, becoming progressively continuous. The slope of the down-to-up transitions, which reflects the speed of recruitment of the local network, was progressively steeper for higher temperatures, whereas wave-propagation speed exhibited only a moderate increase. Fast rhythms were particularly sensitive to temperature. Broadband high-frequency fluctuations in the local field potential were maximal for recordings at 36-38 degrees C. Overall, we found that maintaining cortical slices at physiological temperature is critical for the generated activity to be analogous to that in vivo. We also demonstrate that changes in activity with temperature were not secondary to oxygenation changes. Temperature variation sets the in vitro cortical network at different functional regimes, allowing the exploration of network activity generation and control mechanisms.

Intra-articular injections of hyaluronan solutions of different elastoviscosity reduce nociceptive nerve activity in a model of osteoarthritic knee joint of the guinea pig.

OBJECTIVE: To study in guinea pigs knee joints the effects of intra-articular injection of HYADD 4-G (Fidia-Farmaceutici), a novel hyaluronan (HA)-derived elastoviscous material and of Hyalgan (Fidia-Farmaceutici), a HA product with very low viscoelasticity, on movement-evoked nociceptor impulse activity from normal and inflamed knee joints. DESIGN: Nociceptor impulse activity was recorded from single Adelta and C fibers of the medial articular nerve either under control conditions or after induction of an experimental knee joint osteoarthritis (OA) by partial medial menisectomy and transection of the anterior cruciate ligament (PMM-TACL). The stimuli consisted of standardized innocuous and noxious inward and outward rotations of the tibia against the femur of 50s duration, repeated every 5min for 1.5h. RESULTS: The number of movement-evoked impulses was significantly augmented 1 day and 1 week after PMM-TACL compared with intact knee joint. The enhanced impulse response to joint movements 1 week following surgery was attenuated by repeated intra-articular injection of HYADD 4-G and even more prominently by Hyalgan. CONCLUSIONS: HA products have a reducing action on joint nociceptor discharges that appears to depend predominantly on their role as an elastoviscous filter associated with their rheological properties, but also on a chemical effect on sensitized nociceptive terminals of inflamed joint tissues, possibly linked to the HA concentration.

Differential thermosensitivity of sensory neurons in the guinea pig trigeminal ganglion.

Intracellular recordings were employed to study the effects of temperature on membrane properties and excitability in sensory neurons of the intact guinea pig trigeminal ganglion (TG) maintained in vitro. Neurons were classified according to the shape and duration of the action potential into F (short-duration, fast spike) and S (long duration, slow spike with a "hump") types. Most type F (33/34) neurons had axons with conduction velocities >1.5 m/s, while only 30% (6/23) of type S neurons reached these conduction speeds suggesting differences in myelination. Cooling reduced axonal conduction velocity and prolonged spike duration in both neuronal types. In F-type neurons with strong inward rectification. cooling also increased the excitability, augmenting the input resistance and reducing the current firing threshold. These effects were not observed in S-type neurons lacking inward rectification. In striking contrast to results obtained in cultured TG neurons, cooling or menthol did not induce firing in recordings from the acutely isolated ganglion. However, after application of submillimolar concentrations (100 microM) of the potassium channel blocker 4-aminopyridine (4-AP), 29% previously unresponsive neurons developed cold sensitivity. An additional 31% developed ongoing activity that was sensitive to temperature. Only neurons with strong inward rectification (mostly F-type) became thermosensitive. Cooling- and 4-AP-evoked firing were insensitive to intracellular application of 4-AP or somatic membrane hyperpolarization, suggesting that their action was most prominent at the level of the axon. The lack of excitatory actions of low temperature in the excised intact ganglion contrasts with the impulse discharges induced by cooling in trigeminal nerve terminals of the same species, suggesting a critical difference between cold-transduction mechanisms at the level of the nerve terminals and the soma.

Las sustancias elastoviscosas con efectos analgésicos en el dolor de las articulaciones reducen la actividad in vitro de los canales iónicos activados por estiramiento / Elastoviscous substances with analgesic effects on joint pain reduce stretch-activated ion channel activity in vitro

La activación por estímulos mecánicos dolorosos de las fibras nerviosas sensoriales que transmiten la señal de dolor desde las articulaciones tiene lugar a través de canales iónicos activados por estiramiento, que se abren en respuesta a un aumento de la tensión de la membrana. Se ha sugerido que el efecto analgésico de las soluciones de hialuronano utilizadas para el tratamiento intraarticular del dolor de las articulaciones en el ser humano está mediado por una disminución de la sensibilidad de los canales iónicos mecanosensoriales en las terminaciones nerviosas nociceptivas. Hemos investigado si las soluciones de hialuronano con enlaces cruzados (hilanos) de diferentes elastoviscosidades modifican las características de la respuesta de los canales iónicos activados por estiramiento en oocitos de Xenopus laevis. Para ello, obtuvimos registros con la técnica del pinzamiento zonal ("patch-clamp") en oocitos intactos y en fragmentos de membrana rotos (configuraciones con el exterior hacia fuera y con el interior hacia fuera) en solución de Barth (condición de control) y después de su exposición a hilanos de diferentes elastoviscosidades. Para la estimulación mecánica se aplicó succión controlada a través de la micropipeta y se registró la actividad de los canales activados por estiramiento. Dicha actividad se redujo significativamente en presencia de hilanos de gran elastoviscosidad (contenido de polímeros del 0,8 por ciento, peso molecular de 6M) y de una mezcla de hilano A (90 por ciento en peso) e hilano B (10 por ciento en peso) con un contenido total de polímeros del 0,9 por ciento, un producto utilizado en la práctica clínica. Por el contrario, las soluciones de hilano A con la misma composición química pero menor elastoviscosidad (contenido de polímeros del 0,8 por ciento, peso molecular de 96.000) resultaron ineficaces. Se concluye que los canales activados por estiramiento poseen una menor sensibilidad mecánica en presencia de soluciones elastoviscosas de hilanos, cosa que no ocurre en presencia de soluciones no elastoviscosas de hilanos en la misma concentración. Estos datos sugieren que los efectos analgésicos de la inyección intraarticular de soluciones elastoviscosas de hilanos se deben a una disminución de la sensibilidad a fuerzas mecánicas de los canales activados por estiramiento presentes en la membrana de los mecanonociceptores de las articulaciones. © 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved (AU)

Elastoviscous substances with analgesic effects on joint pain reduce stretch-activated ion channel activity in vitro.

Activation by noxious mechanical stimuli of sensory nerve fibres that signal joint pain takes place through stretch-activated ion channels, which open in response to increased membrane tension. It has been suggested that the analgesic effect of hyaluronan solutions used for intra-articular treatment of joint pain in humans are mediated by a reduction of the sensitivity of mechanosensory ion channels of nociceptive nerve terminals. We have investigated whether cross-linked hyaluronan solutions (hylans) of different elastoviscosities modify the response characteristics of stretch-activated ion channels of Xenopus laevis oocytes. Patch-clamp recordings on intact oocytes and in excised membrane patches (outside-out and inside-out configurations) were performed in Barth's solution (control condition) and after exposure to hylans of different elastoviscosities. For mechanical stimulation, monitored suction was applied through the microelectrode and the activity of stretch-activated channels was recorded. The activity of stretch-activated channels was significantly reduced in the presence of high elastoviscous hylan A (0.8% polymer content, molecular weight 6M) and of a mixture of hylan A (90% by weight) and hylan B (10% by weight), 0.9% total polymer content, a clinically used hylan product. In contrast, solutions of hylan A with the same chemical composition but reduced elastoviscosity (0.8% polymer content, molecular weight 96000) were found ineffective. It is concluded that stretch-activated channels have a decreased mechanical sensitivity in the presence of elastoviscous solutions of hylan, but not in the presence of non-elastoviscous solutions of hylan of the same concentration. These data suggest that the analgesic effects of intra-articular injections of elastoviscous solutions of hylans are due to a reduction of the sensitivity to mechanical forces of stretch-activated channels present in the membrane of joint mechanonociceptors.

Three-dimensional reconstruction of scleral cold thermoreceptors of the cat eye.

Sensory endings that respond to local cooling were identified electrophysiologically in the cat's sclera. Functionally identified scleral thermal fibers were then used to analyze the structural characteristics of cold receptor endings. Four Adelta units sensitive to controlled cooling of their scleral receptive fields were recorded. The receptive areas were mapped, demarcated with pins and examined electron microscopically using extensive three-dimensional reconstructions. The supporting tissue within the receptive areas of cold units consisted of dense collageneous tissue with a small number of blood vessels that were either veins or capillaries. Adelta nerve fibers were found within these tissue blocks presumably corresponding with cold sensitive fibers. Small nerves and single nerve fibers devoid of a perineurium were found in all parts of the tissue, only occasionally passing a blood vessel. The terminal portions showed axonal swellings all along the unmyelinated segment filled with mitochondria, glycogen particles, and some vesicles. About 30% of the terminal axonal membrane is not covered by Schwann cells. In the unmyelinated distal portion, the mitochondrial content ranged from 0.012 to 0.038 microm(3) mitochondrial volume per microm(2) nerve fiber membrane. In comparison with sensory endings in the cat's knee joint, cold receptors in the cat sclera showed many similarities in their three-dimensional structure with polymodal nociceptor endings of the knee joint but contain less mitochondria. This suggests that cold sensory endings do not require specialized cellular processes for the transduction of cold stimuli, as is the case for multimodal transduction and sensitization in the terminal portion of polymodal nociceptors.

Sensations evoked by selective mechanical, chemical, and thermal stimulation of the conjunctiva and cornea.

PURPOSE: To study the sensations evoked by selective mechanical, chemical, and thermal stimulation of the conjunctiva and compare them with those elicited by similar stimulation of the cornea. METHODS: Six young subjects participated in the study. Using a gas esthesiometer, selective mechanical (air puffs at flows from 0 to 264 ml/min), chemical (0--80% CO(2) in air), and thermal (air at temperatures from -10 degrees C to +80 degrees C) stimulation was performed on the center of the cornea and on the temporal conjunctiva. The intensity, degree of irritation, stinging and burning pain components, and thermal characteristics of the evoked sensation were evaluated after each stimulus in separate, 10-cm continuous visual analogue scales (VASs). The ability of the subjects to identify the quality of the stimulus applied to the cornea and the conjunctiva was also studied. RESULTS: The subjective intensity and thermal components (cooling or warming) of the sensation reported after mechanical, chemical, and heat stimulation were similar in the conjunctiva and cornea, although lower VAS scores were always reported in the conjunctiva for the irritation and the stinging and burning pain components. In the cornea, stimulation with low temperatures was perceived as a cooling sensation with an irritative component. In the conjunctiva, cooling was perceived as a purely cold sensation. Subjects showed similar discrimination capability in the cornea and the conjunctiva for the various types of stimuli. CONCLUSIONS: Sensations evoked in the cornea by selective mechanical, chemical, and heat and cold stimulation always presented an irritation component. In the conjunctiva, stimuli of the same intensity are always perceived as less irritating than in the cornea. Cold and other non-noxious subqualities of sensation can be evoked in the conjunctiva.

Sensory experiences in humans and single-unit activity in cats evoked by polymodal stimulation of the cornea.

1. The cornea of human subjects and of anaesthetised cats was stimulated with a jet of air of controlled flow, temperature and CO(2) concentration delivered by a gas aesthesiometer. 2. In humans, the intensity and magnitude of various components of the sensory experience (intensity of the sensation, degree of irritation, magnitude of burning and stinging pain, magnitude of the cold and warm components of the sensation) were measured using separate visual analog scales. In anaesthetised cats, the impulse response to the same stimuli was recorded from single mechanosensory, polymodal and cold-sensitive corneal fibres in the ciliary nerves. 3. Intensity-response curves for mechanical stimulation showed that all parameters of the sensation experienced by humans increased with the intensity of the stimulus. Mechanical stimuli recruited mainly phasic mechanosensory and polymodal afferents in the cat. 4. Acidic stimulation with gas mixtures of increasing CO(2) concentration evoked irritation, burning and to a lesser extent stinging pain of a magnitude roughly proportional to the intensity of the stimulus in humans. CO(2) primarily recruited polymodal afferents and weakly excited cold-sensitive fibres in the cat's cornea. 5. Heat stimuli evoked in humans a sensation profile similar to CO(2) but accompanied by a warmth component. In the cat's cornea, heat excited only polymodal fibres and silenced cold-sensitive corneal units. 6. Cold stimuli applied to the human cornea elicited a sensation of cooling that became irritant at the lowest temperatures. Corneal cold-sensitive fibres of the cat were activated in a manner proportional to the temperature drop, while polymodal nociceptor fibres were recruited only by the lowest temperatures. Topical menthol (0.2 mM) applied to humans evoked and later eliminated cold sensations produced by cold stimuli while the irritation sensation caused by low temperature stimuli still persisted. 7. Human subjects were able to identify masked mechanical, thermal and chemical stimuli applied to the cornea. 8. Irritation and cold sensations can therefore be evoked separately from the cornea by selective activation of mechanosensory, polymodal and cold corneal sensory afferents. Stimulation with different forms of energy usually leads to combined activation and/or inhibition of the different populations of sensory afferent fibres, evoking blended sensations that include irritation and thermal components in a variable degree.

Differences between nerve terminal impulses of polymodal nociceptors and cold sensory receptors of the guinea-pig cornea.

1. Extracellular recording techniques were used to study nerve terminal impulses (NTIs) recorded from single polymodal nociceptors and cold-sensitive receptors in guinea-pig cornea isolated in vitro. 2. The amplitude and time course of NTIs recorded from polymodal nociceptors was different from those of cold-sensitive receptors. 3. Bath application of tetrodotoxin (1 microM) changed the time course of spontaneous NTIs recorded from both polymodal and cold-sensitive receptors. 4. Bath application of lignocaine (lidocaine; 1-5 mM) abolished all electrical activity. 5. Local application of lignocaine (2.5 and 20 mM) through the recording electrode changed the time course of the NTIs recorded from polymodal nociceptors but not that of NTIs recorded from cold-sensitive nerve endings. 6. It is concluded that action potentials propagate actively in the sensory nerve endings of polymodal nociceptors. In contrast, cold-sensitive receptor nerve endings appear to be passively invaded from a point more proximal in the axon where the action potential can fail or be initiated.