Maladaptive Synaptogenesis induced by interaction of voltage gated calcium channel subunit alpha2delta-1 and thrombospondin-4 represents a new mechanism underlying neuropathic pain processing in nerve injury models
Abstract
The molecular basis of neuropathic pain is poorly understood. We have previously shown that nerve injury induces increased production of thrombospondin-4 and voltage-gated calcium channel subunit α2δ-1 and that these proteins play a critical role in mediating behavioral hypersensitivity in animal models. However, the mechanism of action has not been elucidated. I use immunohistochemical staining in nerve injured animal model spinal cords to show that interaction of thrombospondin-4 with α2δ-1 promote excitatory synaptogenesis. Furthermore, I use immunocytochemistry staining in spinal cord and dorsal root ganglia neuron co-culture to show that thrombospondins-4/α2δ-1 interaction mediated synaptogenesis depends on pre-synaptic T-type voltage-gated calcium channel function.