Anatomical and behavioral correlates of the bilateral chronic constriction injury of neuropathic pain in rats

Dorsal horn cholecystokinin (CCK) and NPY are thought to be involved in models of neuropathic pain. However, animal models of neuropathic pain have been problematic. Chronic constriction injury of the sciatic nerve (CCI) has been used extensively as a model of neuropathic pain. Recent operant studies with bilateral CCI (bCCI) showed primarily a prolonged increase in cold sensitivity. Using bCCI of the sciatic nerves, we sought to determine the effect of this injury on responses to three types of cold stimuli (acetone, coldplate, thermal place preference) and to mechanical stimulation. Dorsal horn staining for CCK and NPY was correlated with the behavioral findings. bCCI was produced by 3 snug ligatures of chromic catgut placed on the sciatic nerve trunk. 16 adult rats received bCCI or sham ligation of the sciatic nerve and underwent behavioral testing for up to 80 days. Additional sham and bCCI rats also were sacrificed at 15, 30 and 90 days for anatomical analysis. Acetone testing was performed by applying a drop of acetone to each hindpaw and measuring the frequency of brisk foot withdrawal. Cold plate testing was performed at 0.3°C. In the operant thermal place preference task, animals were allowed to roam freely between two adjacent compartments with opposing floor temperatures maintained at 0.3 or 45oC. Total duration of time spent on the cold side along with total number of crossovers to either side were measured. Mechanical withdrawal thresholds were determined with an electronic von Frey filament. For anatomical studies, rats were sacrificed by transcardiac aldehyde perfusion and lumbar spinal cords were frozen sectioned at 40µm. Parallel one in six series of transverse sections were stained for CCK or NPY using the biotin-avidin-peroxidase method. The results were then analyzed using an automated program to quantify L4 superficial dorsal horn immunoreactivity. Nocicefensive responses ...