Use of central neuromodulators in chronic cough / 中国临床药理学与治疗学

Chronic cough is a common condition that imposes significant physical, psychological, and social burdens on patients. Although chronic cough is often associated with underlying conditions such as asthma, gastroesophageal reflux disease, and eosinophilic bronchitis, some patients experience uncontrollable coughing that is difficult to attribute to a specific cause. Many of these patients exhibit clinical features of cough hypersensitivity syndrome, providing new directions for research into the treatment of chronic cough. As the pathophysiological mechanisms of chronic cough are further elucidated, treatment approaches for chronic cough are entering a new stage of development. This article summarizes and discusses the mechanisms and clinical evidence of central neuromodulators used in the treatment of chronic cough, suggesting promising clinical applications for these drugs in the future.

Impact of treatment optimization in patients with gastroesophageal reflux disease who do not respond to esomeprazole / Impacto de la optimización del tratamiento en pacientes con enfermedad por reflujo gastroesofágico que no responden a esomeprazol

Abstract Introduction: gastroesophageal reflux disease (GERD) affects one out of eight people in Colombia. Its characteristic symptoms are heartburn and reflux. The cornerstone of treatment is proton pump inhibitors (PPIs), with a clinical response in 58-80% of patients. Of those who do not respond, 75-90% have a superimposed functional disorder and could be treated by adding visceral neuromodulators. Objective: to evaluate the impact of optimizing the treatment of patients with GERD when there is no response to esomeprazole (ESO). Materials and methods: a prospective study in patients with no clinical response (more than two reflux episodes per week) who were treated with 40 mg of ESO half an hour before breakfast along with the recommendation to lose weight if BMI >25, stop smoking and manage stress; and, finally, increasing the ESO dose to 40 mg on an empty stomach and before dinner. When all of this was done and symptoms persisted, 12.5 mg of amitriptyline were added at night. The response was evaluated every 12 weeks. Results: a total of 529 patients were eligible and 149 met the inclusion criteria. With treatment optimization, 111 patients had a clinical response without using amitriptyline (74.5%; 95%CI 67.2 81.4). Amitriptyline was added in 22 patients (14.8%), 15 of whom responded (68.2%; 95%CI 47.04-89.32%). Eight patients experienced drowsiness (53.3%). A relationship was found between PPI treatment compliance and clinical response (p<0.0001). Conclusions: in patients with GERD, PPI treatment optimization improves 74.5% (95%CI 67.2 81.4) of the patients, and adding amitriptyline for those who do not improve achieves improvement in 68.2% of those who did not improve with two doses of ESO. Sequential management achieved a cumulative improvement in symptom control in 85% (95%CI 78.6-90.4) of the patients. (Acta Med Colomb 2021; 46. DOI: https://doi.org/10.36104/amc.2021.2041).

Resumen Introducción: la enfermedad por reflujo gastroesofágico (ERGE) afecta a una de cada ocho personas en Colombia. Sus síntomas característicos son pirosis y regurgitación. La piedra angular del tratamiento son los inhibidores de bomba de protones (IBP) con respuesta clínica en 58-80%. En quienes no responden 75-90% tienen un trastorno funcional superpuesto y se podrían tratar adicionando neuromoduladores viscerales. Objetivo: evaluar el impacto que tiene optimizar el tratamiento en pacientes con ERGE cuando no hay respuesta a esomeprazol (ESO). Material y métodos: estudio prospectivo en pacientes sin respuesta clínica (más de dos episodios de reflujo por semana) tratados con ESO 40 mg media hora antes del desayuno y simultáneamente recomendaciones para bajar de peso si IMC >25, dejar de fumar y controlar el estrés, y finalmente aumentado la dosis de ESO a 40 mg en ayunas y antes de la cena. Cuando se cumplió todo lo anterior y persistían los síntomas, se adicionó amitriptilina 12.5 mg por la noche. Cada 12 semanas se evaluaba la respuesta. Resultados: hubo 529 pacientes elegibles y 149 cumplieron los criterios de inclusión. Optimizando el tratamiento 111 pacientes tuvieron respuesta clínica sin la utilización de amitriptilina (74.5%; IC95% 67.2-81.4). En 22 se adicionó amitriptilina (14.8%) y de estos respondieron 15 pacientes, 68.2% (IC95% 47.04-89.32%). En ocho pacientes hubo somnolencia (53.3%). Se encontró relación entre el cumplimiento del tratamiento con IBP y la respuesta clínica (p<0.0001). Conclusiones: en pacientes con ERGE la optimización del tratamiento con IBP mejora el 74.5% (IC95% 67.2-81.4) de los pacientes y la adición de amitriptilina a quienes no mejoran, logra mejorar el 68.2% de quienes no mejoraban con dos dosis de ESO. Con el manejo secuencial se logró mejoría acumulativa en el control de los síntomas de 85% (IC95% 78.6-90.4) de los pacientes. (Acta Med Colomb 2021; 46. DOI:https://doi.org/10.36104/amc.2021.2041).

Sacral Nerve Stimulation for Treatment of Intractable Pain Associated with Cauda Equina Syndrome

Sacral nerve stimulation (SNS) is an effective treatment for bladder and bowel dysfunction, and also has a role in the treatment of chronic pelvic pain. We report two cases of intractable pain associated with cauda equina syndrome (CES) that were treated successfully by SNS. The first patient suffered from intractable pelvic pain with urinary incontinence and fecal incontinence after surgery for a herniated lumbar disc. The second patient underwent surgery for treatment of a burst fracture and developed intractable pelvic area pain, right leg pain, excessive urinary frequency, urinary incontinence, voiding difficulty and constipation one year after surgery. A SNS trial was performed on both patients. Both patients' pain was significantly improved and urinary symptoms were much relieved. Neuromodulation of the sacral nerves is an effective treatment for idiopathic urinary frequency, urgency, and urge incontinence. Sacral neuromodulation has also been used to control various forms of pelvic pain. Although the mechanism of action of neuromodulation remains unexplained, numerous clinical success reports suggest that it is a therapy with efficacy and durability. From the results of our research, we believe that SNS can be a safe and effective option for the treatment of intractable pelvic pain with incomplete CES.

Immunohistochemical analysis of glutamate, cholecystokinin and vasoactive intestinal polypeptide in the lateral geniculate complex of albino rat: A developmental study.

The lateral geniculate nuclear complex of albino rats was investigated with respect to the development of neurotransmitters/neuromodulators such as glutamate, cholecystokinin and vasoactive intestinal polypeptide at gestational day 18, various postnatal age periods and in the adult using immunohistochemical methods. The study shows the unequivocal presence of and the sequential changes in the profile of glutamate while cholecystokinin and vasoactive intestinal polypeptide are not demonstrable at any of the age periods. Glutamate is seen both in the cells and fibres from 40 postnatal day onwards and immunoreactivity is more intense in the adult. The findings are discussed with relevance to the role of neurotransmitters in development.

SOMATOSTATIN IN SYNAPTIC STRUCTURES OF SUBSTANTIA GELATINOSA OF THE SPINAL CORD / 解剖学报

The distribution of somatostatin (SRIF) in substantia gelatinosa of the rat spinal cord was studied by means of immuno-electron microscopy. The ultrastructural features showed that nerve terminals containing SRIF take part in forming presynap- tie elements of axe-somatic, axe-dendritic and axo-axonic synapses. The immune- reactive products locatl at the external membrane of mitochondria, around the small clear synaptie vesicles and in the large granular vesicles. Most of synaptic vesicles are round or ovoid in shape. Only a few of them are flattened. Based on the ultrastructural characteristics mentioned above and related experimental results the authors believe that SRIF in substantia gelatinosa of the rat spinal cord is probably involved as a neurotransmitter instead of neuromodulator.