Dissecting the Neural Circuitry for Pain Modulation and Chronic Pain: Insights from Optogenetics / 神经科学通报·英文版

Pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. The processing of pain involves complicated modulation at the levels of the periphery, spinal cord, and brain. The pathogenesis of chronic pain is still not fully understood, which makes the clinical treatment challenging. Optogenetics, which combines optical and genetic technologies, can precisely intervene in the activity of specific groups of neurons and elements of the related circuits. Taking advantage of optogenetics, researchers have achieved a body of new findings that shed light on the cellular and circuit mechanisms of pain transmission, pain modulation, and chronic pain both in the periphery and the central nervous system. In this review, we summarize recent findings in pain research using optogenetic approaches and discuss their significance in understanding the pathogenesis of chronic pain.

Advance in Role of Neuropeptide Y Receptors System in Pain Modulation (review) / 中国康复理论与实践

@#The neuropeptide Y receptors system is a receptor-ligand system composed of neuropeptide Y and its receptors, which is represented by two subtypes, including Y1 receptor (Y1R) and Y2 receptor (Y2R). The system is widely involved in pain modulation in mammals. These receptors are G protein-coupled receptors, participating in neuronal membrane signaling. Neuropeptide Y receptors distribute in the pain-related regions of the central nervous system, play a variety of roles in maintains neuronal activity of pain transmission, relate to the specificity of distribution. At the spinal level, Y1R plays an analgesic role, whereas Y2R is usually related to pain-promoting. The system can also take part in cerebral pain modulation at different nuclei.

Somatosensory, inflammatory and pain evaluation during orthodontic treatment / Avaliação das alterações dolorosas, inflamatórias e somatossensoriais em pacientes durante tratamento ortodôntico

Experimental tooth movement has been shown to induce inflammation and release of chemical mediators. Inflammation can also alter nerve function that can be measured with Quantitative Sensory Testing (QST). Various authors have studied orthodontic pain and the different factors that modify it. But, to our knowledge none studied a possible individual endogenous analgesia effect on orthodontic induced-pain. The aim of the present study was to investigate the impact of orthodontic separator and short-term fixed orthodontic appliance on the somatosensory function and gingival cervicular fluid (GCF) levels of IL-1ß, IL-8, IL-6 and TNF-α. Thirty patients were evaluated as follow: baseline, 24h-after elastomeric separator (24h-aES), 24h and 1 month after bonding the fixed appliance (aBFA) at maxillary and mandibular arch. The outcome variables were: self-reported pain, QSTs (current perception threshold, cold detection threshold, warm detection threshold, mechanical detection threshold, mechanical supra threshold and wind-up ratio, CPM and sample from the GCF in order to assess cytokines profile (IL-1ß, IL-8, IL-6 and TNF-α). ANOVA and Tukey's post hoc analyses were performed (a = 5%). The participants were divided in two groups: G1) RESPONDERS (more than 10% decrease in WUR); G2) NON-RESPONDERS (not show more than 10% decrease in WUR). T-test for independent sample was performed. A Bonferroni correction lowered the significance level to 0.1% (p = 0.001) as the cut-off point to establish the statistical significance for the mean difference between CPM responders and non-responders. Patients were less sensitive to pin prick pain (MST) at 24h (p<0.020) and 1month-aBFA (p<0.002) when compared to baseline. Significant increases in IL-6 levels were observed 24h-aBFA (p<0.023) and in IL-1ß (p<0.001) and TNF-α (p<0.026) levels at 1 month-aBFA when compared to baseline values (p<0.023). There was no significant difference in somatosensory function, pain report and GCF cytokines when compared between G1 and G2. In conclusion, orthodontic-induced inflammation may have a modality specific effect on somatosensory function of the trigeminal system. In addition, elastic separators seem not an ideal model to study possible inflammatory changes following orthodontic tooth movement. Moreover, CPM efficiency may not significantly influence somatosensory function, pain intensity or released of inflammatory cytokines following orthodontic tooth movement up to 1 month. However, remained to be confirmed and further investigations are required in intraoral somatosensory assessment.(AU)

O movimento dentário experimental demonstrou induzir inflamação e liberação de mediadores químicos. A inflamação também pode alterar a função nervosa que pode ser medida através de testes quantitativos sensoriais (QST). Vários autores estudaram a dor ortodôntica e os diferentes fatores que a modificam. Mas, ao nosso conhecimento, não há estudos avaliando o efeito da analgesia endógena individual na dor induzida por ortodontia. O objetivo do presente estudo foi investigar o impacto do separador ortodôntico e do aparelho ortodôntico fixo de curta duração na função somatossensorial e nos níveis do fluido cervical gengival (GCF) de IL-1ß, IL-8, IL-6 e TNF-α. Trinta pacientes foram avaliados da seguinte forma: valores basais, 24 horas após separador elástico (24h- AES), 24h e 1 mês após a ligação do aparelho fixo (aBFA) no arco maxilar e mandibular. As variáveis avaliadas foram: dor, QSTs (limiar de percepção elétrica, limiar de detecção ao frio, limiar de detecção ao quente, limiar de detecção mecânica, supralimiar mecânico e razão de somação temporal, CPM e amostra do GCF para avaliar perfil das citocinas ( IL-1ß, IL-8, IL-6 e TNF-α). A ANOVA e as análises post hoc de Tukey foram realizadas (a = 5%). Os participantes foram divididos em dois grupos: G1) CPM-RESPONDENTES (diminuição de mais de 10% em WUR); G2) CPM-NÃO RESPONDENTES (não mostra mais de 10% de diminuição na WUR). Foi realizado teste T para amostra independente. Uma correção de Bonferroni reduziu o nível de significância para 0,1% (p = 0,001) como ponto de corte para estabelecer a significância estatística para a diferença média entre G1 o G2. Os pacientes eram menos sensíveis à dor de pin (MST) às 24h (p <0,020) e 1 mês-aBFA (p <0,002) quando comparado à linha de base. Observaram-se aumentos significativos nos níveis de IL-6 níveis 24h-aBFA (p <0,023) e nos níveis de IL-1ß (p <0,001) e TNF-α (p <0,026) em 1 mês-aBFA quando comparados aos valores basais (p < 0,023). Não houve diferença significativa na função somatossensorial, no relatório da dor e citocinas do FCG quando comparadas entre G1 e G2. Em conclusão, a inflamação induzida por ortodontia pode ter um efeito de modalidade específico na função somatossensorial do sistema trigeminal. Além disso, os separadores elásticos não parecem ser um modelo ideal para estudar possíveis alterações inflamatórias após o movimento dentário ortodôntico. Além disso, a eficiência de CPM pode não influenciar significativamente a função somatossensorial, intensidade da dor ou liberação de citocinas inflamatórias após o movimento dentário ortodôntico até 1 mês. No entanto, outras investigações são necessárias na avaliação somatossensorial intraoral.(AU)

Factors influencing conditioned pain modulation and chronic pain / 基础医学与临床

As a new laboratory test for evaluation of endogenous pain inhibition,conditioned pain modulation (CPM) deficiency means dysfunction of endogenous pain inhibitory systems and higher incidence of chronic pain.Age,psychological factors and physical activity all seem to influence the individual CPM effect.A standard CPM testing way has an important role in comparison between different researches.

Armonización corporal en prematuros con sindrome de distres respiratorio (SDR) Hospital de la Mujer, La Paz Bolivia / Body harmonizationin premature babies with breathings distress syndrome (SDR) Woman's Hospital, La Paz- Bolivia

PREGUNTA DE LA INVESTIGACIÓN: ¿La técnica de Armonización Corporal con al tratamiento clínico convencional es de mayor beneficio, en relación al tratamiento clínico convencional exclusivo en prematuros? OBJETIVOS: Establecer eficacia de la Técnica de Armonización Corporal en prematuros con SDR. DISEÑO: Ensayo clínico controlado. LUGAR: Neonatología - Hospital de la Mujer, La Paz, Bolivia. POBLACIÓN: 314 Neonatos prematuros con distrés respiratorio. MUESTRA: No probabilístico, por conveniencia: 106 pacientes 53 grupo tratamiento 53, grupo control MÉTODOS: Técnica de armonización corporal a prematuros. RESULTADOS: Saturación: ODDS RATIO=4.24, Chi-cuadrado=12,44 mejora saturación. Oxigeno: ODDS RATIO=2.96, Chi-cuadrado=6,86 menos días oxígeno. Evolución: ODDS RATIO=4.14, Chi-cuadrado=12,27 evolución positiva. CONCLUSIONES: Se comprobó: La técnica de armonización corporal es eficaz en el distrés respiratorio de prematuros del Hospital de la Mujer asociada al tratamiento clínico convencional.

RESEARCH QUESTION: Is the body harmonization technique with conventional clinical treatment more beneficial, in relation with the exclusive conventional clinical treatment in premature babies? OBJETIVE: To establish the effectiveness of the body harmonization technique in premature babies? DESIGN: Controlled clinical test. LOCATION: Neonatology - Woman's Hospital, La Paz, Bolivia. POPULATION: 314 premature newborn with breathing distress syndrome (SDR). SAMPLING: Non probabilistic, by convenience: 106 patients, 53 treatments, 53 control group. METHOD: Body harmonization technique to premature babies. RESULTS: Saturation: ODDS RATIO=4.24, Chi-squared=12,44 improves saturation. OXYGEN: ODDS RATIO=2.96, Chi-squared=6,86 less oxygen days. EVOLUTION: ODDS RATIO=4.14, Chi-squared=12,27 positive evolution. CONCLUSION: It was proved: Body harmonization technique is effective in breathing distress of premature babies at the Woman's Hospital related to conventional clinical treatment

The implementation of the Neuroid in the Gate Control System leads to new ideas about pain processing

INTRODUCTION: Several theories have been proposed to elucidate the mechanisms related with pain perception, among which, the Gate Control Theory (GCT) provides one of the most explicit explanations. This theory, as elegantly conceived, is unable to explain how the Frequency-Intensity (F-I) curves exhibited by Aβ- and C-fibres influence pain processing. In this paper, a novel neuron-model known as the Neuroid, which emphasizes the functional rather the physiological character of nerve cells, was used as the main building block to replicate the Gate Control System (GCS). METHODS: Two Aβ-fibre models were built: one model that preserved the paradoxical relation between the activation threshold and the F-I curve slope, and one model based on the hypothetical average response across the receptive field. RESULTS: The results suggest that the average response of the Aβ-fibres does not increase monotonically but reaches a plateau for high intensity stimuli. In addition, it was seen that activation of C-fibres does not necessarily imply the activation of projection neurons and, therefore, the onset of pain sensation. Also, we observed that the activation of Aβ-fibres may both, decrease and increase the activity of the projections neurons, an aspect which has not been directly described in previous works. CONCLUSION: Hypothetical implications arise as a consequence of the implementation of the Neuroid, specifically, about the correlation between the intensity of stimulation and the physiological pain threshold.

Cardiovascular drugs in human mechanical nociception: digoxin, amlodipine, propranolol, pindolol and atenolol

Calcium channel blockers, β adrenergic receptor blockers and Na/K ATPase inhibitors are widely used drugs, mainly for cardiovascular diseases. Their pharmacological targets are not restricted to the cardivascular tissue, nociceptive system structures also express similar targets, which strongly suggests a direct effect on pain sensation. To evaluate the pain intensity changes in outpatient groups, who receive these drugs as a therapy, a cross-sectional sampled, randomized patient groups receiving the calcium channel blocker amlodipine for blood hypertension (n=45), β adrenergic receptor blockers (propranolol, atenolol or pindolol; n=40) for blood hypertension, or digoxin (n=40) for heart failure, were compared to an aparently healthy volunteers control group (n=60). A calibrated noxious pressure of 890 g/mm² was applied for 5 seconds on the patient’s sternum. Subjective pain intensity was reported by the visual analog scale (VAS, 0 to 10). Pain modulation system was evaluated by the application of a second stimulus with a 5 minutes delay. The analgesic effect of the β blockers group (propanolol, atenolol, pindolol) was dosage-dependant (-36.8 percent; P=0.0000003), without differences among them. The calcium channel blocker amlodipine showed lower pain scores (-50.6 percent; P=0.0000003) than β-receptor blockers (P=0.0000003). Digoxin presented the highest pain scores (+56.5 percent; P=0.0000003). All pain scores for the second stimulus were lower than the first stimulus and were differentially affected by β-blockers (atenolol, pindolol and propanolol) and calcium channel blocker (amlodipine), but not by digoxin. These results suggest the influence of widely clinically used cardiovascular drugs on nociception.

Los bloqueadores de los canales de calcio, los bloqueadores de los receptores β adrenérgicos y los inhibidores de la ATPasa Na/K son medicamentos ampliamente usados en enfermedades cardiovasculares. Sus blancos farmacológicos no se restringen al tejido cardiovascular, el sistema nervioso nociceptivo expresa blancos similares, lo que sugiere fuertemente un efecto directo en la sensación del dolor. El objetivo del presente estudio fue evaluar los cambios en la intensidad del dolor en grupos de pacientes ambulatorios que reciban estos medicamentos como terapia. Grupos aleatorios de pacientes que reciben el bloqueador de canales de calcio amlodipina contra la hipertensión arterial (n=45), bloqueadores de receptores β adrenérgicos (propranolol, atenolol or pindolol; n=40) contra la hipertensión arterial o digoxina (n=40) por insuficiencia cardíaca fueron comparados con un grupo control de voluntarios aparentemente sanos (n=60). A todos los grupos se les aplicó una presión nociva calibrada de 890 g/mm² durante 5 segundos sobre el esternón. El paciente reportó la intensidad subjetiva del dolor mediante la escala visual análoga (VAS). El sistema de modulación descendente del dolor fue evaluado mediante la aplicación del mismo estímulo 5 minutos después del primero. Se determinó un efecto analgésico en el grupo de β bloqueantes (propanolol, atenolol, pindolol) dosis dependiente (-36,8 por ciento; P=0,0000003) sin mostrar diferencias entre ellos. El bloqueador de canales de calcio amlodipina mostró un efecto analgésico (-50,6 por ciento; P=0,0000003) que fue mayor que el de los β bloqueantes (P=0,0000003). El grupo con digoxina expresó un efecto hiperalgésico (+56,5 por ciento; P=0,0000003). Todos los valores de dolor para el segundo estímulo fueron menores que para el primero y fueron diferencialmente afectados por los β bloqueantes (atenolol, pindolol and propanolol) y por la amlodipina pero no por la digoxina. Estos...