Research on the pathological mechanisms of nerve decompression in relieving tactile allodynia in diabetic rats

Objectives To explore the pathological mechanism of peripheral nerve decompression in relieving tactile allodynia in diabetic rats. Methods Healthy adult male Sprague Dawley rats were randomly divided into 5 groups for different interventions: group Ⅰ (healthy control, n=10), group Ⅱ (diabetes model, n=20), group Ⅲ (diabetes model with latex tube placement, n=10), group Ⅳ (diabetes model with latex tube placement and nerve decompression, n=10), group V (diabetes model with latex placement and merely operational area exposure, n=10). The diabetes model was induced by intraperitoneal injection of streptozotocin (STZ). Nerve decompression was performed by removal of latex tube encircling the sciatic nerve at 3 weeks post model establishment. The paw withdrawal threshold was tested 3 days after modeling with the use of "up-down" method. Diabetic rats with tactile allodynia in 4 experimental groups (groups Ⅱ-Ⅳ) were preserved. Morphometric analysis of myelinated and non-myelinated nerve fibers was performed with the use of projection electron microscope. Western blot and immunofluorescence were used to localized and determined the expression of GABAB receptor protein in spinal dorsal horn. Results Three weeks after operation, the incidence of tactile allodynia in STZ-induced rats[55.0%(11/20)] was lower than that in diabetic rats with latex tube placement (groups Ⅲ, Ⅳ and Ⅴ) [86.7%(26/30), χ2=6.254, P=0.012]. The paw withdrawal threshold in group Ⅰ (13.41±1.88 g) was higher than those in groups Ⅱ-Ⅳ (4.06±1.28 g, 3.09±1.43 g, 4.02±1.96 g, 4.15±1.87 g respectively, P<0.05). At 5 weeks post operation, the paw withdrawal threshold in group Ⅳ was higher than those of group Ⅱ, Ⅲ and Ⅴ(all P<0.05). When compared with group Ⅰ, smaller myelinated fibers area and density, as well as higher g-ratio were revealed by electron microscope in each experimental group (all P<0.05). Larger myelinated fiber area and density, as well as lower g-ratio were noted in group Ⅳ when compared with those in group Ⅱ and Ⅴ (all P<0.05). The results of western blot showed that lower expression of GABAB receptor was noted in experimental groups (Ⅱ, Ⅲ, Ⅳ and Ⅴ) when compared with group Ⅰ (all P<0.05), and higher expression of GABAB receptor in both NF-200+ areas and neurons of spinal dorsal horn was noted in group Ⅳ when compared with group V (P<0.05) at 3 weeks post nerve decompression. The results of immunofluorescence showed that lower expression of GABAB receptor in both NF-200+ areas and neurons of spinal dorsal horn was noted in experimental groups (Ⅱ, Ⅲ, Ⅳ and Ⅴ) when compared with group Ⅰ (all P<0.05). Conclusions Peripheral nerve decompression can relieve the tactile allodynia of diabetic rats mainly by removing the compression damage of myelinated nerve fibers, lifting the GABAB receptor downregulation-mediated central sensitivity, thereby relieving the pathological state of elevated spinal excitability. Key words: Diabetes mellitus; Disease models, animal; Tactile allodynia; Nerve decompression