Altered parabrachial nucleus nociceptive processing may underlie central pain in Parkinson's disease.

The presence of central neuropathic pain in Parkinson's disease suggests that the brain circuits that allow us to process pain could be dysfunctional in the disorder. However, there is to date no clear pathophysiological mechanism to explain these symptoms. In this work, we present evidence that the dysfunction of the subthalamic nucleus and/or substantia nigra pars reticulata may impact nociceptive processing in the parabrachial nucleus (PBN), a low level primary nociceptive structure in the brainstem, and induce a cellular and molecular neuro-adaptation in this structure. In rat models of Parkinson's disease with a partial dopaminergic lesion in the substantia nigra compacta, we found that the substantia nigra reticulata showed enhanced nociceptive responses. Such responses were less impacted in the subthalamic nucleus. A total dopaminergic lesion produced an increase in the nociceptive responses as well as an increase of the firing rate in both structures. In the PBN, inhibited nociceptive responses and increased expression of GABAA receptors were found following a total dopaminergic lesion. However, neuro-adaptations at the level of dendritic spine density and post-synaptic density were found in both dopaminergic lesion groups. These results suggest that the molecular changes within the PBN following a larger dopaminergic lesion, such as increased GABAA expression, is a key mechanism to produce nociceptive processing impairment, whilst other changes may protect function after smaller dopaminergic lesions. We also propose that these neuro-adaptations follow increased inhibitory tone from the substantia nigra pars reticulata and may represent the mechanism generating central neuropathic pain in Parkinson's disease.

Single-pulse electrical stimulation methodology in freely moving rat.

BACKGROUND: Cortico-cortical evoked potentials (CCEP) are becoming popular to infer brain connectivity and cortical excitability in implanted refractory epilepsy patients. Our goal was to transfer this methodology to the freely moving rodent. NEW METHOD: CCEP were recorded on freely moving Sprague-Dawley rats, from cortical and subcortical areas using depth electrodes. Electrical stimulation was applied using 1 ms biphasic current pulse, cathodic first, at a frequency of 0.5 Hz, with intensities ranging from 0.2 to 0.8 mA. Data were then processed in a similar fashion to human clinical studies, which included epoch selection, artefact correction and smart averaging. RESULTS: For a large range of tested intensities, we recorded CCEPs with very good signal to noise ratio and reproducibility between animals, without any behavioral modification. The CCEP were composed of different components according to recorded and stimulated sites, similarly to human recordings. COMPARISON WITH EXISTING METHODS: We minimally adapted a clinically-motivated methodology to a freely moving rodent model to achieve high translational relevance of future preclinical studies. CONCLUSIONS: Our results indicate that the CCEP methodology can be applied to freely moving rodents and transferred to preclinical research. This will be of interest to address various neuroscientific questions, in physiological and pathological conditions.

Design and Performance Assessment of a Solid-State Microcooler for Thermal Neuromodulation.

It is well known that neural activity can be modulated using a cooling device. The applications of this technique range from the treatment of medication-resistant cerebral diseases to brain functional mapping. Despite the potential benefits of such technique, its use has been limited due to the lack of suitable thermal modulators. This paper presents the design and validation of a solid-state cooler that was able to modulate the neural activity of rodents without the use of large and unpractical water pipes. A miniaturized thermal control solution based exclusively on solid-state devices was designed, occupying only 5 mm × 5 mm × 3 mm, and featuring the potential for wireless power and communications. The cold side of the device was cooled to 26 °C, while the hot side was kept below 43 °C. This range of temperatures is compatible with brain cooling and efficient enough for achieving some control of neural activity.