Amapola, lindísima amapola: de los opiáceos y los opioides, utilidad y riesgos / Poppy, beautiful poppy: opiates and opioids, utility and risks

Resumen El opio y sus derivados, y recientemente los opioides, han acompañado a la humanidad desde las civilizaciones más antiguas hasta la actualidad. Sus efectos analgésicos, hipnóticos y placenteros no pasaron desapercibidos para los antiguos, los consideraron de utilidad médica y beneficiosa para el estado de ánimo. Hoy en día no existe otro tipo de medicamentos que puedan tratar el dolor más intenso tan eficientemente como estos potentes analgésicos. Sin embargo, el uso médico y recreativo de los opiáceos y los opioides conlleva riesgos para la salud, como la tolerancia, la hiperalgesia y la adicción. Actualmente, además de ser indiscutiblemente el tratamiento médico más poderoso para mitigar el sufrimiento ocasionado por el dolor, se ha convertido también en un problema de salud pública debido a la alta cantidad de personas con trastorno por uso de opioides y por las muertes ocasionadas por sobredosis. En esta revisión se hará mención de las bondades de los opiáceos y opioides, y también de los efectos no deseados que estos producen.

Abstract Opium and its derivatives, and recently the opioids have accompanied the humankind since the ancient civilizations to the present day. Its analgesic, hypnotic and pleasant effects did not go unnoticed by ancient people, which considered most of these effects of medical utility and noticed that they had remarkable mood benefits. Currently, there are no other kind of drugs that can palliate intense pain as efficiently as these powerful analgesics. However, the medical and recreational use of opiates and opioids may carry health risks such as tolerance, hyperalgesia, and addiction. Nowadays, in addition to being indisputably the most powerful medical treatment to alleviate the suffering caused by pain, it has also become a public health problem due to the high number of people with opioid use disorder that have facilitated deaths caused by opioids overdose. In this review we will discuss the medical benefits of opiates and opioids, as much as the unwanted effects they produce.

Response to Hypoxic Preconditioning of Glial Cells from the Roof of the Fourth Ventricle.

The cerebellum harbors a specialized area on the roof of the fourth ventricle that is composed of glial cells and neurons that interface with the cerebrospinal fluid. This region includes the so-called ventromedial cord (VMC), which is composed of cells that are glial fibrillary acidic protein (GFAP)-positive and nestin-positive and distributes along the midline in association with blood vessels. We hypothesized that these cells should compare to GFAP and nestin-positive cells that are known to exist in other areas of the brain, which undergo proliferation and differentiation under hypoxic conditions. Thus, we tested whether cells of the VMC would display a similar reaction to hypoxic preconditioning (HPC). Indeed, we found that the VMC does respond to HPC by reorganizing its cellular components before it gradually returns to its basal state after about a week. This response we documented by monitoring global changes in the expression of GFAP-EGFP in transgenic mice, using light-sheet fluorescence microscopy (LSFM) revealed a dramatic loss of EGFP upon HPC, and was paralleled by retraction of Bergmann glial cell processes. This EGFP loss was supported by western blot analysis, which also showed a loss in the astrocyte-markers GFAP and ALDH1L1. On the other hand, other cell-markers appeared to be upregulated in the blots (including nestin, NeuN, and Iba1). Finally, we found that HPC does not remarkably affect the incorporation of BrdU into cells on the cerebellum, but strongly augments BrdU incorporation into periventricular cells on the floor of the fourth ventricle over the adjacent medulla.

The effect of carmustine on Bergmann cells of the cerebellum.

Administration of the alkylating agent carmustine to pregnant mice induces hyperlocomotion in the offspring. Motor performance was evaluated by the rotarod task, which revealed that these animals have diminished Grab Frequency and a higher Performance Index, whereas Error of Latency and Latency to Fall were unaffected. Considering the recently revealed role of Bergmann cells of cerebellum in the control of motor activity, we used the transgenic mice GFAP-GFP to explore the impact of carmustine on the organization of these glial cells. Multiple examples of cell layer disorganization were detected; many soma of Bergmann cells were displaced to the external cell layer, and their processes were not well defined until young adulthood. In addition, the roof of the fourth ventricle was convoluted. These observations suggest that the exacerbated locomotion induced by carmustine may be due, in part, to the altered organization of the cell layers of cerebellum.