RESUMO
Neuropathic pain is a common diabetic complication affecting 8-16% of diabetic patients. It is characterized by aberrant symptoms of spontaneous and stimulus-evoked pain including hyperalgesia and allodynia. Magnesium (Mg) deficiency has been proposed as a factor in the pathogenesis of diabetes-related complications, including neuropathy. In the central nervous system, Mg is also a voltage-dependent blocker of the N-methyl-d-aspartate receptor channels involved in abnormal processing of sensory information. We hypothesized that Mg deficiency might contribute to the development of neuropathic pain and the worsening of clinical and biological signs of diabetes and consequently, that Mg administration could prevent or improve its complications. We examined the effects of oral Mg supplementation (296 mg l(-1) in drinking water for 3 weeks) on the development of neuropathic pain and on biological and clinical parameters of diabetes in streptozocin (STZ)-induced diabetic rats. STZ administration induced typical symptoms of type 1 diabetes. The diabetic rats also displayed mechanical hypersensitivity and tactile and thermal allodynia. The level of phosphorylated NMDA receptor NR1 subunit (pNR1) was higher in the spinal dorsal horn of diabetic hyperalgesic/allodynic rats. Magnesium supplementation failed to reduce hyperglycaemia, polyphagia and hypermagnesiuria, or to restore intracellular Mg levels and body growth, but increased insulinaemia and reduced polydipsia. Moreover, it abolished thermal and tactile allodynia, delayed the development of mechanical hypersensitivity, and prevented the increase in spinal cord dorsal horn pNR1. Thus, neuropathic pain symptoms can be attenuated by targeting the Mg-mediated blockade of NMDA receptors, offering new therapeutic opportunities for the management of chronic neuropathic pain.
Assuntos
Diabetes Mellitus Experimental/complicações , Neuropatias Diabéticas/prevenção & controle , Hiperalgesia/prevenção & controle , Magnésio/uso terapêutico , Neuralgia/prevenção & controle , Receptores de N-Metil-D-Aspartato/metabolismo , Administração Oral , Animais , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/fisiopatologia , Modelos Animais de Doenças , Temperatura Alta , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Magnésio/administração & dosagem , Masculino , Neuralgia/metabolismo , Neuralgia/fisiopatologia , Fosforilação , Ratos , Ratos Sprague-Dawley , Estreptozocina , Estresse MecânicoRESUMO
Procyanidins extracted from the rhizomes of Potentilla tormentilla were fractionated according to their degree of polymerization by chromatography on Sephadex LH20. Dimers and trimers displayed the highest anti-radical activity towards lipoperoxidation. Pentamers and hexamers possessed the most marked anti-elastase properties.