Zona Incerta: A Role in Central Pain

Abstract

pain syndrome (CPS) is a debilitating condition that affects a large number of patients with a primary lesion or dysfunction in the CNS. Despite its discovery over a century ago, the pathophysiological processes underlying the development and maintenance of CPS are poorly understood. We recently demonstrated that activity in the posterior thalamus (PO) is tightly regulated by inhibitory inputs from zona incerta (ZI). Here we test the hypothesis that CPS is associated with abnormal inhibitory regulation of PO by ZI. We recorded single units from ZI and PO in animals with CPS resulting from spinal cord lesions. Consistent with our hypothesis, the spontaneous firing rate and somatosensory evoked responses of ZI neurons were lower in lesioned animals compared with sham-operated controls. In PO, neurons recorded from lesioned rats exhibited significantly higher spontaneous firing rates and greater responses to noxious and innocuous stimuli applied to the hindpaw and to the face. These changes were not associated with increased afferent drive from the spinal trigeminal nucleus or changes in the ventroposterior thalamus. Thus CPS can result from suppressed inputs from the inhibitory nucleus zona incerta to the posterior thalamus.

Cell Cycle Activation Contributes to Increased Neuronal Activity in the Posterior Thalamic Nucleus and Associated Chronic Hyperesthesia after Rat Spinal Cord Contusion

“…We obtained single-unit, electrophysiological recordings from urethane-anesthetized rats, as previously described [24,50,61]. Consistent with our previous findings after electrolytic lesions of the spinothalamic tract [13], SCI significantly increased both spontaneous and sensory-evoked responses of PO neurons, as evidenced by comparing peri-stimulus time histograms (Fig.…”

“…Thus, contusion SCI produces similar abnormalities in PO thalamus as those seen after selective electrolytic lesion of the spinothalamic tract [24], consistent with the hypothesis that changes of thalamic activity are causally related to development of SCI pain [13,62].…”

“…At least 45 days after SCI, rats were anesthetized with urethane and prepared for extracellular recordings as previously described [24,50]. We selected urethane because it has no, or negligible, effects on glutamatergic and gamma-aminobutryic acid (GABA)ergic transmission, and therefore produces only minimal disruption of signal transmission [51].…”

“…The posterior nucleus (PO) of the thalamus receives convergent innocuous and noxious somatosensory inputs by way of the spinothalamic tract (STT), the major ascending pain pathway [22,23]. We have previously reported increased spontaneous and sensory-evoked activity in PO that is associated with CPS induced by unilateral focal electrolytic lesions in the rat STT [24]. We also provided evidence that these changes are caused by reduced inhibitory inputs to PO, and that they are causally related to the experience of pain in these animals [13].…”

Peripheral nerve injury induces adult brain neurogenesis and remodelling

“…Electrophysiological evidence suggests that C‐fibre stimulation activates the mossy fibre input from the pontine nuclei 33, and that both A‐fibre and C‐fibre stimulation activates the climbing fibres 34, which transmit information from the inferior olive to the cerebellum. In addition, the zona incerta and the periaqueductal grey, two brain regions that deliver major inputs to the inferior olives, are known to relay both ascending nociceptive information 35, 36, 37, as well as descending cortical signals.…”