Motor cortex stimulation is generally suggested as a therapy for patients with chronic and refractory neuropathic pain. However, the mechanisms underlying its analgesic effects are still unknown. In a previous study, we demonstrated that cortical stimulation increases the nociceptive threshold of naive conscious rats with opioid participation. In the present study, we investigated the neurocircuitry involved during the antinociception induced by transdural stimulation of motor cortex in naive rats considering that little is known about the relation between motor cortex and analgesia. The neuronal activation patterns were evaluated in the thalamic nuclei and midbrain periaqueductal gray. Neuronal inactivation in response to motor cortex stimulation was detected in thalamic sites both in terms of immunolabeling (Zif268/Fos) and in the neuronal firing rates in ventral posterolateral nuclei and centromedian-parafascicular thalamic complex. This effect was particularly visible for neurons responsive to nociceptive peripheral stimulation. Furthermore, motor cortex stimulation enhanced neuronal firing rate and Fos immunoreactivity in the ipsilateral periaqueductal gray. We have also observed a decreased Zif268, δ-aminobutyric acid (GABA), and glutamic acid decarboxylase expression within the same region, suggesting an inhibition of GABAergic interneurons of the midbrain periaqueductal gray, consequently activating neurons responsible for the descending pain inhibitory control system. Taken together, the present findings suggest that inhibition of thalamic sensory neurons and disinhibition of the neurons in periaqueductal gray are at least in part responsible for the motor cortex stimulation-induced antinociception.

No abstract

No abstract

In previous work we showed that apoptosis in retinal tissue from developing rats can be induced by inhibition of protein synthesis (Rehen et al. 1996, Development, 122, 1439-1448). Here we show that recent postmitotic cells are the cells sensitive to apoptosis triggered by blockade of protein synthesis. To label all proliferating cells in the retina, a series of injections of the nucleotide analogue, bromo-deoxy-uridine (BrdU, 60 mg/kg b.w.), was given in rat pups. Then, explants of the retina were incubated in vitro with the inhibitor of protein synthesis anisomycin (1.0-3.2 microg/mL) for 1 day to induce apoptosis. Detection of apoptotic bodies under differential interference contrast microscopy was combined with immunocytochemistry for BrdU, proliferating cell nuclear antigen (PCNA) or for various markers of retinal cell differentiation. Despite the large number of BrdU- and PCNA-labelled cells in the tissue, the vast majority of the cells that underwent apoptosis were postmitotic cells which have left the mitotic cycle 3-4 days before. However, these cells were not labelled with antibodies to calretinin, calbindin, rhodopsin or to a Muller glial cell marker, suggesting that these are early postmitotic neurons. We suggest that during migration and initial differentiation, the apoptotic machinery is blocked by suppressor proteins, thus allowing recent postmitotic cells to find their final positions and differentiate while protected from apoptosis.

NADPH oxidase (Nox) is a unique, multi-protein, electron transport system that produces large amounts of superoxide via the reduction of molecular oxygen. Nox-derived reactive oxygen species (ROS) are known to be involved in a variety of physiological processes, including host defense and signal transduction. However, over the past decade, the involvement of (Nox)-dependent oxidative stress in the pathophysiology of several neurodegenerative diseases has been increasingly recognized. ROS produced by Nox proteins contribute to neurodegenerative diseases through distinct mechanisms, such as oxidation of DNA, proteins, lipids, amino acids and metals, in addition to activation of redox-sensitive signaling pathways. In this review, we discuss the recent literature on Nox involvement in neurodegeneration, focusing on Parkinson and Alzheimer diseases.