Post-translational modification of cortical GluA receptors in rodents following spinal cord lesion.

Previous studies investigating the pathophysiology of neuropathic pain caused by injury to the spinal cord suggest that pain may result, at least in part, from maladaptive plasticity in the somatosensory cortex and associated pain networks. However, little is known about the molecular and cellular mechanisms leading to maladaptive plasticity in the cortex and how they contribute to the development of neuropathic pain. AMPA-type glutamate receptors (GluARs) mediate fast excitatory synaptic transmission in the mammalian brain and play an important role in pain processing. Here we used an electrolytic lesion model of spinal cord injury in animals to study the expression and phosphorylation of GluA1 and 2 in the primary somatosensory cortex (S1). Experiments in rats and mice revealed that maladaptive plasticity and hypersensitivity after spinal cord lesion (SCL) are associated with a reduction in the fraction of GluA1 subunits that are phosphorylated at serine 831 (S831) in the hindlimb representation of S1 (S1HL). Manipulations that reduce the fraction of phosphorylated S831 in S1HL of non-lesioned animals, including low-frequency electrical stimulation and viral-mediated gene transfer of mutant S831, were associated with the development of hypersensitivity. Taken together, these findings suggest that phosphorylation of GluA1 at S831 plays an important role in the development of hypersensitivity after SCL.