Caracterización de la expresión del receptor de Neurotrofinas P75 en modelo murino de dolor neuropático.
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Date
2024
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Universidad de Concepción
Abstract
El dolor neuropático, una aflicción con impacto significativo en la calidad de vida de los pacientes, surge de una lesión o enfermedad del sistema somatosensorial. La señalización molecular del dolor crónico ha sido vinculada con alteraciones en la expresión y función de neurotrofinas y sus receptores Trks y p75, de alta y baja afinidad respectivamente. Durante el dolor neuropático, incrementa la expresión de neurotrofinas junto a sus receptores específicos Trks. Sin embargo, aun cuando existe evidencia que relaciona la participación de p75 en la regulación neurofisiológica del dolor, su estudio no ha sido ampliamente abordado. Esta investigación caracterizó la expresión y función del receptor p75 durante el dolor neuropático en modelos murinos, enfocándose principalmente en los cambios moleculares que ocurren en la medula espinal. Los resultados obtenidos mostraron un incremento de la expresión de p75 en la médula espinal, la expresión de este receptor en las láminas más externas del asta dorsal y la activación de proteínas ERK, implicadas en la mantención del dolor neuropático a través del tiempo. Al comprender la participación del receptor p75 en la neurofisiología del dolor, se busca contribuir al estudio de las neurotrofinas en el dolor neuropático y colaborar en la propuesta de nuevos blancos terapéuticos para la neurofarmacología del dolor.
Neuropathic pain, an affliction with significant impact on patients' quality of life, arises from injury or disease of the somatosensory system. Molecular signalling in chronic pain has been linked to alterations in the expression and function of neurotrophins and their high- and low-affinity receptors Trks and p75, respectively. During neuropathic pain, neurotrophin expression increases along with their specific Trks receptors. However, although there is evidence linking the involvement of p75 in the neurophysiological regulation of pain, its study has not been widely addressed. This research characterised the expression and function of the p75 receptor during neuropathic pain in murine models, focusing mainly on the molecular changes that occur in the spinal cord. The results obtained showed an increase in p75 expression in the spinal cord, the expression of this receptor in the outermost laminae of the dorsal horn and the activation of ERK proteins, which are involved in the maintenance of neuropathic pain over time. By understanding the participation of the p75 receptor in the neurophysiology of pain, we aim to contribute to the study of neurotrophins in neuropathic pain and collaborate in the proposal of new therapeutic targets for the neuropharmacology of pain.
Neuropathic pain, an affliction with significant impact on patients' quality of life, arises from injury or disease of the somatosensory system. Molecular signalling in chronic pain has been linked to alterations in the expression and function of neurotrophins and their high- and low-affinity receptors Trks and p75, respectively. During neuropathic pain, neurotrophin expression increases along with their specific Trks receptors. However, although there is evidence linking the involvement of p75 in the neurophysiological regulation of pain, its study has not been widely addressed. This research characterised the expression and function of the p75 receptor during neuropathic pain in murine models, focusing mainly on the molecular changes that occur in the spinal cord. The results obtained showed an increase in p75 expression in the spinal cord, the expression of this receptor in the outermost laminae of the dorsal horn and the activation of ERK proteins, which are involved in the maintenance of neuropathic pain over time. By understanding the participation of the p75 receptor in the neurophysiology of pain, we aim to contribute to the study of neurotrophins in neuropathic pain and collaborate in the proposal of new therapeutic targets for the neuropharmacology of pain.
Description
Tesis presentada para optar al título de Bioquímico/a.
Keywords
Factores de Crecimiento Nervioso, Dolor Crónico, Médula Espinal, Sistema Nervioso Central, Sistema Nervioso Periférico