Analysis of the behavioral, cellular and molecular characteristics of pain in severe rodent spinal cord injury.

摘要: Human SCI is frequently associated with chronic pain that severe and refractory to medical therapy. Most rodent models used assess outcomes in apply moderate injuries lower thoracic spinal levels, whereas the majority of human lesions are degree occur at cervical or upper levels. To better model understand mechanisms after SCI, we subjected adult rats T3 compression complete transection lesions, examined pain-related behaviors for three months. Within one week injury, developed consistent forepaw including increased spontaneous lifts, tactile allodynia cold sensitivity persisted Place escape avoidance testing confirmed withdrawal forepaws from a von Frey stimulus represented active aversion. Spontaneous evoked measures were attenuated by gabapentin, further indicating these reflect development pain. Spinal level injury was relevant: T11 did not exhibit behaviors. Immunoblotting immunofluorescence C6-C8 dorsal horn, reflecting sensory innervation forepaw, revealed: 1) expansion CGRP immunoreactivity lamina I/II; 2) GAP-43 expression; 3) IBA1, GFAP connexin-43 expression. These findings indicate aberrant fiber sprouting gliopathy SCI. Notably, satellite glial cells (SGCs) DRGs exhibited increases connexin-43, suggesting ongoing peripheral sensitization. Carbenoxolone, gap junction inhibitor, specific peptide inhibitors ameliorated established Collectively, successfully persistent states could constitute useful system examining candidate translational therapies