Central pain syndrome (CPS) is a debilitating condition that affects a large number of patients with a primary lesion or dysfunction in the CNS, most commonly due to spinal cord injury, stroke, and multiple sclerosis lesions. The pathophysiological processes underlying the development and maintenance of CPS are poorly understood. We have recently shown, in an animal model of CPS, that neurons in the posterior thalamic nucleus (PO) have increased spontaneous and evoked activity. We also demonstrated that these changes are due to suppressed inhibitory inputs from the zona incerta (ZI). The anterior pretectal nucleus (APT) is a diencephalic nucleus that projects on both the PO and ZI, suggesting that it might be involved in the pathophysiology of CPS. Here we test the hypothesis that CPS is associated with abnormal APT activity by recording single units from APT in anesthetized rats with CPS resulting from spinal cord lesions. The firing rate of APT neurons was increased in spinal-lesioned animals, compared with sham-operated controls. This increase was due to a selective increase in firing of tonic neurons that project to and inhibit ZI and an increase in bursts in fast bursting and slow rhythmic neurons. We also show that, in normal animals, suppressing APT results in increased PO spontaneous activity and evoked responses in a subpopulation of PO neurons. Taken together, these findings suggest that APT regulates ZI inputs to PO and that enhanced APT activity during CPS contributes to the abnormally high activity of PO neurons in CPS.
Maladaptive Homeostatic Plasticity in a Rodent Model of Central Pain Syndrome: Thalamic Hyperexcitability after Spinothalamic Tract Lesions
