Decreases of glycine receptor expression induced by median nerve injury in the rat cuneate nucleus contribute to NPY release and c-Fos expression

Aims: This study aimed to investigate temporal changes in glycine and its receptor expressions in cuneate neurons after median nerve transection (MNT), and the effects of glycine on neuropeptide Y (NPY) release and c-Fos expression in the cuneate nucleus (CN). Main methods: Immunohistochemistry methods were used to appraise changes of glycine- and GlyR-like immunoreactive (LI) neurons in the CN after MNT. The alterations in NPY and c-Fos expressions were used to assess the effects of saline, glycine or strychnine treatment. The CatWalk method was used to assess the efficiency of glycine treatment on the neuropathic signs of rats with MNT. Key findings: Approximately half of GlyR-LI neurons were fluorogold-labeled cuneothalamic projection neurons in the CN. Following MNT, the number of GlyR-LI neurons significantly decreased in the injured side of CN at 2 and 4 weeks, but the number of glycine-LI neurons remained unchanged. Four weeks after MNT given with electrical stimulation, strychnine significantly decreased the NPY reduction level in the stimulated side CN compared to that of the saline group. However, numbers of c-Fos-LI neurons in the glycine and strychnine groups were both significantly less than that in the saline group. But the paw print width and area in CatWalk analysis showed only a moderate recovery. Significance: We conjecture that glycine increases glycine-mediated postsynaptic inhibition of cuneate neurons, and also blocks GABAergic neurons containing GlyRs which mediate presynaptic inhibition causing temperate NPY release. Consequently, the compromise results showed a weak reduction in c-Fos expression and a slight amelioration of neuropathic behaviors.