Summary: Researchers have identified a novel, pain sensing network that links the subthalamic nucleus to a pain processing network in mouse models of Parkinson’s disease.
Scientists have revealed a novel brain network that links pain in Parkinson’s disease (PD) to a specific region of the brain, according to a report in the journal eLife.
The research reveals why a subset of neurons in part of the brain called the subthalamic nucleus is a potential target for pain relief in PD, as well as other diseases such as dementia, motor neuron disease and Huntington’s, and certain forms of migraine.
People with PD often report unexplained pain such as burning, stabbing, aching, itching or tingling sensations that are not directly related to their other PD symptoms. Treatment with deep brain stimulation in the subthalamic nucleus can help with the movement-related symptoms of PD, but recent studies have shown it also reduces pain. The way it does this, however, is currently unclear.
“In this study, we set out to determine whether the subthalamic nucleus is involved in translating a harmful stimulus such as injury into pain, and whether this information transmission is altered in PD,” explains lead author Arnaud Pautrat, PhD Student at Grenoble Institut des Neurosciences (Inserm, National Institute for Health and Medical Research/University Grenoble Alpes), France.
The team started by using electrophysiology to measure the firing of electrical signals in nerve cells in the subthalamic nucleus of rats given a shock to their back paw. Nerve cells were indeed temporally activated by this stimulation. They also found that the neurons fell into three response groups, showing an increase, decrease or no change in their baseline firing rate.
They next looked at whether these responses caused a change in brain function. Rats with a damaged subthalamic nucleus took much longer to show signs of discomfort than healthy rats. When they expanded their study to rat models of PD, the team found that nerve cells in the subthalamic nucleus had higher firing rates and the responses to pain were bigger and longer than in the healthy animals. Taken together, this suggests that dysfunctional pain-processing pathways in the subthalamic nucleus are the cause of PD-related pain.
To understand where the pain signals to the subthalamic nucleus were coming from, the team looked at two brain structures known to be important in relaying damage signals from the spinal cord: the superior colliculus and the parabrachial nucleus. Blocking their activity revealed that both structures play a crucial role in transmitting pain information to the subthalamic nucleus, and that a direct communication pathway exists between the parabrachial nucleus and the subthalamic nucleus. As a result, the team believes this pathway is likely to be involved in the beneficial effects of deep brain stimulation on pain in PD and that these novel insights could help to target stimulation to specific parts of the brain to make it more effective as a pain reliever.
“We have found evidence that the subthalamic nucleus is functionally linked to a pain-processing network and that these responses are affected in Parkinsonism,” concludes senior author and Inserm researcher Veronique Coizet, PhD. “Further experiments are now needed to fully characterise the effects deep brain stimulation on this brain region in our experimental models, with a view to finding ways to optimise it as a treatment for pain caused by Parkinson’s and other neurological diseases.”
Funding: Institut National de la Santé et de la Recherche Médicale, ADR Région Rhône Alpes, UGA AGIR-POLE funded this study.
Source: Emily Packer – eLife
Publisher: Organized by NeuroscienceNews.com.
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Original Research: Abstract for “Revealing a novel nociceptive network that links the subthalamic nucleus to pain processing” by Arnaud Pautrat, Marta Rolland, Margaux Barthelemy, Christelle Baunez, Valérie Sinniger, Brigitte Piallat, Marc Savasta, Paul G Overton, Olivier David, and Veronique Coizet in eLife. Published August 28 2018.
Revealing a novel nociceptive network that links the subthalamic nucleus to pain processing
Pain is a prevalent symptom of Parkinson’s disease, and is effectively treated by deep brain stimulation of the subthalamic nucleus (STN). However, the link between pain and the STN remains unclear. In the present work, we report that STN neurons exhibit complex tonic and phasic responses to noxious stimuli using in vivo electrophysiology in rats. We also show that nociception is altered following lesions of the STN, and characterize the role of the superior colliculus and the parabrachial nucleus in the transmission of nociceptive information to the STN, physiologically from both structures and anatomically in the case of the parabrachial nucleus. We show that STN nociceptive responses are abnormal in a rat model of PD, suggesting their dependence on the integrity of the nigrostriatal dopaminergic system. The STN-linked nociceptive network we reveal is likely to be of considerable clinical importance in neurological diseases involving a dysfunction of the basal ganglia.