Author's Name: Diana Gasca

Chronic Pain Changes the Brain Researchers at the Institute for Biomedical Research and Innovation at Cádiz (INiBICA), affiliated with the University of Cádiz (UCA) and the CIBER Mental Health Network (CIBERSAM), have identified neural connections responsible for modulating pain and depressive symptoms resulting from chronic pain. The studies, led by Professor Esther Berrocoso and the late Professor Juan Antonio Micó, culminated in the publication of “Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons” in the prestigious journal *Brain*. It is well known that many patients with chronic pain are susceptible to mental health conditions, such as depression or anxiety disorders. However, the neurobiological mechanisms involved remain poorly understood, making effective treatment difficult. For this reason, this research group has focused on studying the biological mechanisms involved in one type of pain—neuropathic pain—whose therapeutic management remains highly complex. This pain can have various causes: as a result of nerve compression (for example, due to a tumor, a herniated disc, or carpal tunnel syndrome), or it may result from nerve damage affecting the entire body (diabetes mellitus), a specific area (pain due to shingles [herpes zoster]), or even abnormal processing of pain signals, as occurs in phantom limb pain. Researchers are focusing their studies on the locus coeruleus, the central nervous system’s primary noradrenergic nucleus, which plays a key role in pain processing and connects the spinal cord to cortical areas responsible for the sensory and emotional processing of pain. Using innovative methodological approaches such as DREADDs (an acronym for Designer Receptors Exclusively Activated by Designer Drugs), which allow for the selective modulation of neuronal activity, they have demonstrated that the connections between the locus coeruleus and the spinal cord play a significant role in pain relief only at the onset of neuropathy, suggesting that endogenous analgesic function becomes depleted. Furthermore, interrupting the connection between the locus coeruleus and the anterior cingulate cortex alleviates the depressive behavior observed in animals with neuropathic pain. Similarly, a pharmacological study demonstrated the involvement of alpha-adrenergic receptors in the anterior cingulate cortex responsible for the depressive phenotype. These results demonstrate that chronic pain causes various changes in the central nervous system over time. Thus, in the early stages of the pain process, adaptations mediated by the descending noradrenergic pathway to the spinal cord occur, reducing the pain experienced by the subject. However, when the pain process persists over time, connections from the locus coeruleus to the anterior cingulate cortex are activated, which may promote the onset of depression-related symptoms. In other words, norepinephrine has a beneficial analgesic effect at the spinal level but can be counterproductive in higher brain areas, causing undesirable effects. These findings may help explain why current antineuropathic drugs that promote noradrenergic activation require complementary mechanisms of action, such as the modulation of ion channels (gabapentin), serotonergic systems (amitriptyline or duloxetine), or even opioids (tapentadol and tramadol). Furthermore, this study demonstrates the importance of seeking new personalized therapeutic approaches to curb the chronicity of pain and associated mental health conditions.

Puerto Real University Hospital, through its Obstetrics and Gynecology Department, in collaboration with the Endocrinology and Nutrition Department, has developed a predictive model via an app that calculates the risk of developing gestational diabetes, which is the most common endocrine disorder during pregnancy. Andalusia has a program to detect gestational diabetes in pregnant women; specifically, universal screening is conducted using the so-called O’Sullivan test, which is a glucose tolerance test involving a 50-gram glucose load. If the O’Sullivan test is positive, a complete glucose tolerance test must be performed, involving a 100-gram glucose load and blood glucose measurements while fasting, and one hour, two hours, and three hours after consuming the glucose. The significant advances made in recent years thanks to Big Data—which encompasses a series of techniques that attempt to mathematically model information to obtain a result—have enabled the INiBICA research group from the Department of Obstetrics and Gynecology, in collaboration with the Department of Endocrinology and Nutrition, both based at the Portorreal center, to develop a predictive model that, using simple variables available during the first trimester of pregnancy, makes it possible to determine the probability that a woman will develop diabetes during pregnancy. The model is now available for professional use (intended for specialists in gynecology, endocrinology, primary care, midwives, etc.) as a mobile app and can be downloaded for free for both Android and iOS from the App Store under the name DIAGESTACIONAL. According to Juan Jesús Fernández, head of the Obstetrics and Gynecology Department, the results obtained in the cross-validation of the calculator are very promising, and if these results are confirmed in external validation, the developed algorithm could help in the future to determine which patients should undergo an oral glucose tolerance test and which should not. 🔗 More information: Diario de Cádiz

Thanks to the positive response this year to Rolucan’s initiative to sell charity T-shirts in observance of World Breast Cancer Day, which was celebrated on October 19, this association was able to meet its goal of donating a portion of the proceeds to research aimed at finding a cure for breast cancer. In total, 3,000 euros were raised and donated to the Foundation for the Management of Biomedical Research and Innovation at Cádiz (which manages the Institute for Biomedical Research and Innovation at Cádiz), which has already received this contribution to continue the research so desperately needed to combat this disease. Last week, members of Rolucan’s board of directors—including its president, Toñi López, as well as María del Mar Patino and Patro Peña—visited the Puerta del Mar Hospital in Cádiz, where the foundation is located on the ninth floor. Thanks to Dr. José Manuel Baena Cañada —an oncologist and member of the Team research team whom they contacted—they were able to make this donation. For Rolucan, as they had already announced on the day the charity T-shirt was unveiled, a top priority was to do their part for research—as they have been doing since 2015, when the Charity Run and Walk Against Breast Cancer in Rota first began. Over the course of the five editions held so far, the public’s response has been a resounding success, which has made these contributions possible while also allowing the association to continue its work. Donating this money—the result of the solidarity of an entire town like Rota—brings great satisfaction to those who work daily at Rolucan to improve the quality of life for local cancer patients. For this reason, the remaining funds raised from the sale of the 2,500 T-shirts will be allocated to the annual maintenance of two essential services for this community—physical therapy and psychological counseling—which are offered at their headquarters at the El Molino Municipal Social Center. Rolucan wished to express its gratitude to all those who, through their contributions, supported this charitable cause—even without the race or the charity walk taking place, they chose to purchase the “pink warrior” T-shirt at the center—a reference to this year’s design, created by María Díaz—and wear it on October 19 through the streets of Rota. In the spirit of transparency that this cancer-fighting association upholds in its operations, it has reported on how the funds were allocated—a feat that would have been impossible without the support of Rota’s residents. For this reason, they have expressed their deepest gratitude to everyone who purchased the T-shirt, to their sponsors—Hevetia and Rota Casa—and to the Rota City Council. 🔗 More information: Rota al día

Dr. Irati Hervás Corpión and Dr. Luis Miguel Valor Becerra, in collaboration with Drs. Irene Iglesias Lozano, Inmaculada Catalina Fernández, and José Luis Gil Salú (specialists from the Neurosurgery and Pathology Departments at the Hospital Universitario Puerta del Mar de Cádiz) along with other researchers, have identified the induction of histone variants known as H3.1 and H3.2 in glioblastoma samples, compared to lower-grade gliomas. Among gliomas, glioblastoma is the most common brain cancer and has the poorest prognosis, despite current intensive therapeutic interventions. The results of this research, published in the journal *Cancers* and funded by INiBICA’s own research program and the Carlos III Health Institute—European Regional Development Fund 2014–2020, have been validated in patients from the province of Cádiz and open the possibility of their future implementation as part of routine glioma diagnosis, as well as future research to define their potential as therapeutic targets. 🔗 More information: PubMed

INiBICA researchers have identified a therapeutic target for the treatment of accelerated aging, known as progeria. The INiBICA group led by Mario Cordero has demonstrated the role of the NLRP3 inflammasome complex in this devastating disease and shown how its potential treatment extends lifespan in animal models. The study, published in the prestigious journal EMBO Molecular Medicine, is part of a project funded by the Progeria Research Foundation.

La investigadora del INIBICA Lucia Olvera Collantes del grupo de investigación liderado por el catedrático de la Universidad de Cádiz e investigador del INIBICA Francisco García Cózar, ha fabricado los virus que se han utilizado para demostrar que es posible la detección en gotas de fluidos y en residuos secos sobre superficies. El trabajo cuyos resultados han sido publicados en la revista Scientific Reports (Nature Publishing Group), ha sido liderado por el profesor Emilio Gómez González, catedrático de Física Aplicada de la Escuela Técnica Superior de Ingeniería de la Universidad de Sevilla y se basa en el registro de imágenes hiperespectrales en el rango visible e infrarrojo cercano y su procesado mediante algoritmos de estadística avanzada e inteligencia artificial. La fabricación de virus inocuos basados en lentivirus, pero con la proteína spike del SARS-Cov-2 en la envoltura, ha permitido realizar la experimentación sin correr los riesgos que se derivarían del uso de virus naturales. El trabajo ha sido financiado en el marco del Proyecto C-CLEAN liderado por el Prof. Gómez-González y la fabricación de los virus se ha desarrollado en el contexto del proyecto NANOCOMPETE, liderado por el Dr. Garcia-Cozar, ambos financiados gracias a la Convocatoria Fondo Covid FIS del Instituto de Salud Carlos III, dependiente del Ministerio de Ciencia e Innovación. Los investigadores continúan trabajando activamente en el análisis de muestras humanas con SARS-CoV-2. 🔗 Más información: Nature

Un proyecto del INiBICA, liderado por el Dr. Mario Cordero, ha sido seleccionado por la Progeria Research Foundation (PRF) en su programa de becas y ayudas para la investigación del Síndrome de Envejecimiento Prematuro o Progeria. El proyecto pretender investigar el papel de los inflamasomas en la progeria y el potencial de los inhibidores de NLRP3 para el tratamiento de esta devastadora enfermedad.

El grupo de investigación del INiBICA, liderado por el Dr. Mario D. Cordero, en colaboración con la Unidad de Nefrología del Hospital Puerta del Mar de Cádiz, obtiene la beca 2021 para la investigación de la Sociedad Andaluza de Trasplante de Órganos y Tejidos (SATOT) por un proyecto de investigación para el estudio de los inflamasomas en el trasplante renal. La beca, dotada de 8000 euros, ayudará a investigar el papel de estos complejos proteicos en el rechazo al trasplante.