RESUMEN
Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain unclear. There is increasing evidence implicating the involvement of spinal endomorphin-2 (EM2) in neuropathic pain. In this study, we used a vincristine-evoked rat CNP model displaying mechanical allodynia and central sensitization, and observed a significant decrease in the expression of spinal EM2 in CNP. Also, while intrathecal administration of exogenous EM2 attenuated allodynia and central sensitization, the mu-opioid receptor antagonist ß-funaltrexamine facilitated these events. We found that the reduction in spinal EM2 was mediated by increased activity of dipeptidylpeptidase IV, possibly as a consequence of chemotherapy-induced oxidative stress. Taken together, our findings suggest that a decrease in spinal EM2 expression causes the loss of endogenous analgesia and leads to enhanced pain sensation in CNP.
Asunto(s)
Oligopéptidos/metabolismo , Médula Espinal/metabolismo , Vincristina/toxicidad , Animales , Antineoplásicos Fitogénicos/toxicidad , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/metabolismo , Electrofisiología , Técnica del Anticuerpo Fluorescente , Hiperalgesia/inducido químicamente , Hiperalgesia/metabolismo , Hiperalgesia/patología , Immunoblotting , Técnicas para Inmunoenzimas , Inyecciones Espinales , Masculino , Neuralgia/inducido químicamente , Neuralgia/metabolismo , Neuralgia/patología , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Médula Espinal/efectos de los fármacosRESUMEN
The protective effects of hyperbaric oxygenation following traumatic brain injury have been widely investigated; however, few studies have made systematic comparisons between the different hyperbaric oxygenation manipulations and their corresponding effects. In this study, male Sprague-Dawley rats were observed at 4h, 15d and 75d after traumatic brain injury. The effects of the different hyperbaric oxygenation manipulations on the rats were compared based on morphological, molecular biological and behavioral tests. Our results showed that hyperbaric oxygenation inhibited cell apoptosis in the rat hippocampus and improved their physiological functions. The effects observed in the hyperbaric oxygen-early group were better than the hyperbaric oxygen-delayed group, and the hyperbaric oxygen-early-delayed group demonstrated the best effects among all the groups. Our results showed the hyperbaric oxygenation was recommended early and delayed post-traumatic brain injury and exposure to hyperbaric oxygenation should be prolonged. These findings provide new ideal therapeutic insight for the clinical treatment of traumatic brain injury.