Neuroplasticity of ascending and descending pathways after somatosensory system injury: reviewing knowledge to identify neuropathic pain therapeutic targets.

STUDY DESIGN: This is a narrative review of the literature. OBJECTIVES: This review aims to be useful in identifying therapeutic targets. It focuses on the molecular and biochemical neuroplasticity changes that occur in the somatosensory system, including ascending and descending pathways, during the development of neuropathic pain. Furthermore, it highlights the latest experimental strategies, based on the changes reported in the damaged nociceptive neurons during neuropathic pain states. SETTING: This study was conducted in Girona, Catalonia, Spain. METHODS: A MEDLINE search was performed using the following terms: descending pain pathways; ascending pain pathways; central sensitization; molecular pain; and neuropathic pain pharmacological treatment. RESULTS AND CONCLUSION: Neuropathic pain triggered by traumatic lesions leads to sensitization and hyperexcitability of nociceptors and projection neurons of the dorsal horn, a strengthening in the descendent excitatory pathway and an inhibition of the descending inhibitory pathway of pain. These functional events are associated with molecular plastic changes such as overexpression of voltage-gated ion channels, algogen-sensitive receptors and synthesis of several neurotransmitters. Molecular studies on the plastic changes in the nociceptive somatosensory system enable the development of new pharmacological treatments against neuropathic pain, with higher specificity and effectiveness than classical drug treatments. Although research efforts have already focused on these aspects, additional research may be necessary to further explore the potential therapeutic targets in neuropathic pain involved in the neuroplasticity changes of neuropathological pathways from the injured somatosensory system.

Epigallocatechin-3-gallate treatment reduces thermal hyperalgesia after spinal cord injury by down-regulating RhoA expression in mice.

BACKGROUND: (-)-Epigallocatechin-3-gallate (EGCG) is the major polyphenolic constituent found in green tea. It has been reported that may be a natural agent for reducing thermal and mechanical pain after nervous system injuries. However, the molecular pathways implicated in these beneficial effects have not been completely elucidated. This study aimed to assess the EGCG treatment effects on thermal hyperalgesia, spinal cord gliosis and modulation of Ras homologue gene family member A (RhoA), fatty acid synthase (FASN) and tumour necrosis factor alpha (TNF-α) expression after spinal cord contusion in mice. METHODS: Animals were subjected to a spinal cord contusion. Thirty minutes after contusion and daily during the first week post-surgery, animals were treated with EGCG or dimethyl sulfoxide-saline (DMSO-saline). At 7 and 14 days post-operation, motor recovery was evaluated using the Basso Mouse Scale, and nociceptive response was evaluated using the Hargreaves test. Furthermore, at 14 days, the expression of RhoA, FASN and TNF-α proteins was quantified in the lesion site of spinal cord by Western blot technique. Finally, spinal cord samples were processed by immunohistochemical techniques for observing astrocytes, microglia and afferent nerve fibres. RESULTS: At short time, EGCG treatment reduced significantly thermal hyperalgesia but had no effect on locomotor recovery in spinal cord injured mice. Furthermore, EGCG treatment down-regulated the RhoA, FASN and TNF-α proteins expression, and decreased astro- and microglia reactivity in spinal cord. CONCLUSION: These findings suggest that at short time EGCG treatment reduces thermal hyperalgesia and gliosis via FASN and RhoA pathway, causing a decrease in cytokines in spinal cord.

[Cardiovascular risk and the new diagnostic categories for diabetes mellitus proposed by the American Diabetes Association]. / Riesgo cardiovascular asociado a las nuevas categorías diagnósticas de la diabetes mellitus propuestas por la Asociación Americana de Diabetes.

OBJECTIVE: To study the cardiovascular risk (CVR) associated with the diagnostic criteria for diabetes proposed by the American Diabetes Association. DESIGN: Cross-sectional, descriptive study. SETTING: Urban health district. PATIENTS: 1840 patients > 14 years old, selected by simple randomised sampling from the clinical records (CR) archive, were studied. METHOD: Through review of the CR, the patients were classified as having: normal glycaemia, disturbed basal glycaemia (DBG) and type-2 diabetes mellitus (DM2). CVR was studied through the simplified Framingham method and the CVR factors of obesity, tobacco dependency, hypertension, hypercholesterolaemia and hypertriglyceridaemia. The likelihood of having high or very high CVR and the CVR factors described in the patients with DBG or DM2 were compared with the same in those with normal glycaemia, through logistical regression with the odds ratio adjusted for age and sex. RESULTS: 1351 patients were classified: 995 with normal glycaemia, 146 with DBG and 210 with DM2. Patients with DBG or DM2 had greater likelihood of high or very high CVR, with some OR at 2.26 (95% CI, 1.39-3.69) and 2.74 (95% CI, 1.81-4.15), respectively. They also had differences (p < 0.05) for obesity (OR, 1.76 and 1.58), hypertension (OR, 1.75 and 2.15) and hypertriglyceridaemia (OR, 1.73 and 2.70), respectively. There were no differences (p > 0.05) for tobacco dependency and hypercholesterolaemia. No differences were found (p > 0.05) between DBG and DM2 for CVR and the CVR factors studied. CONCLUSIONS: Patients with DBG and DM2 are at high CVR.

Riesgo cardiovascular asociado a las nuevas categorías diagnósticas de la diabetes mellitus propuestas por la asociación americana de diabetes / Cardiovascular risk and the new diagnostic categories for diabetes mellitus proposed by the american diabetes association

Objetivo. Estudiar el riesgo cardiovascular (RCV) asociado a las categorías diagnósticas de la diabetes propuestas por la Asociación Americana de Diabetes. Diseño. Estudio descriptivo, transversal. Emplazamiento. Área básica de salud (ABS) urbana. Pacientes. Se estudiaron 1.840 pacientes 15 años, seleccionados por muestreo aleatorio simple del archivo de historias clínicas (HC). Método. Mediante revisión de la HC se clasificó a los pacientes en normoglucemia, glucemia basal alterada (GBA) y diabetes mellitus tipo 2 (DM2). Se estudió el RCV mediante el método de Framingham simplificado y los factores de RCV obesidad, tabaquismo, hipertensión arterial, hipercolesterolemia y hipertrigliceridemia. La probabilidad de tener un RCV elevado o muy elevado y los factores de RCV descritos en los pacientes con GBA y DM2 respecto a los normoglucémicos se estudiaron mediante regresión logística, ajustando la odds ratio (OR) por edad y sexo. Resultados. Se clasificó a 1.351 pacientes: 995 normoglucémicos, 146 pacientes GBA y 210 pacientes DM2. Los pacientes con GBA y DM2 tuvieron una probabilidad superior de presentar un RCV elevado o muy elevado, con unas OR de 2,26 (IC del 95 por ciento, 1,39-3,69) y 2,74 (IC del 95 por ciento, 1,81-4,15), respectivamente. También presentaron diferencias (p 0,05) respecto al tabaquismo y la hipercolesterolemia. No se detectaron diferencias (p > 0,05) entre GBA y DM2 respecto al RVC y los factores de RCV estudiados. Conclusiones. Los pacientes con GBA y DM2 tienen un elevado RCV (AU)