Central pain modulation after subthalamic nucleus stimulation

Marqués, Ana; Chassin, Olivier; Morand, Dominique; Pereira, Bruno; Debilly, Bérengère; Derost, Philippe; Ulla, Miguel; Lemaire, Jean‐Jacques; Durif, Franck

doi:10.1212/wnl.0b013e3182a08d00

Cited by 70 publications

(50 citation statements)

References 38 publications

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“…Because PD can affect brainstem nuclei involved in pain perception, nociceptive information cannot be relayed directly from the spinal cord to higher centers (Brefel‐Courbon et al, ; Baron et al, ). DBS has been shown to improve pain symptoms in PD patients (Gierthmuhlen et al, ; Ciampi de Andrade et al, ), and a recent study revealed, by evaluating pain thresholds (thermal and mechanical) and motor symptoms in a double‐blind, randomized, crossover design, that this improvement relies on a central mechanism (Marques et al, ). Animal experiments also have shown that stimulating the substantia nigra leads to nociceptive inhibition by activating the spinal cord neurons through dopaminergic pathways (Barnes et al, ; Burkey et al, ; Ferrucci et al, ).…”

Section: Treatment Strategiesmentioning

confidence: 99%

Sensory symptoms in Parkinson's disease: Clinical features, pathophysiology, and treatment

Zhu

et al. 2016

J of Neuroscience Research

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Parkinson's disease (PD) is one of the most common forms of neurodegenerative disease in the elderly population and is typically manifested by motor symptoms and nonmotor symptoms and signs. Nonmotor symptoms, such as sensory symptoms, have been regarded as the significant features of this disease. These symptoms often occur in early stages of PD and influence quality of life. However, researchers suggest that the sensory symptoms of PD are frequently unrecognized by clinicians and remain untreated. The disorders include pain, olfactory disturbance, and visual dysfunction input on the underlying sensory abnormality. This Review focuses on the clinical features, pathophysiological mechanisms, and treatment strategies for sensory symptoms of PD from both clinical studies and basic research, providing a comprehensive overview of the sensory symptoms in PD. © 2016 Wiley Periodicals, Inc.

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Section: Treatment Strategiesmentioning

confidence: 99%

Sensory symptoms in Parkinson's disease: Clinical features, pathophysiology, and treatment

Zhu

et al. 2016

J of Neuroscience Research

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“…Recent studies since 2013 included the post‐hoc analysis of the RECOVER trial, which suggested that rotigotine patch significantly improved pain in PD patients, as measured by a Likert pain scale . In a crossover RCT of 19 PD patients, a significant increase of pain threshold was found after acute STN‐DBS as well as after acute l ‐dopa administration. There was no significant correlation between postoperative clinical pain improvement and UPDRS‐III improvement, suggesting that this effect may be owing to direct central modulation of pain perception.…”

Section: New Treatments and Discoveriesmentioning

confidence: 99%

New clinical trials for nonmotor manifestations of Parkinson's disease

Schrag¹,

Sauerbier

Chaudhuri

2015

Movement Disorders

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Nonmotor manifestations in Parkinson's disease (PD) encompass a range of clinical features, including neuropsychiatric problems, autonomic dysfunction, sleep disorders, fatigue, and pain. Despite their importance for patients' quality of life, the evidence base for their treatment is relatively sparse. Nevertheless, the last few years have seen a number of new trials starting that specifically address nonmotor features as an outcome measure in clinical trials. Large randomized, controlled trials in the last 3 years reported improvement of psychosis with the new selective serotonin 5‐HT2A inverse agonist pimavanserin and of postural hypotension with the oral norepinephrine precursor droxidopa. Smaller new randomized, controlled trials support the effectiveness of Deep Brain Stimulation and opiates for pain, of rivastigmine for apathy and piribedil for apathy post‐DBS, group cognitive behavioral therapy for depression and/or anxiety, continuous positive airway pressure for sleep apnea in PD and doxepin for insomnia, and of solifenacin succinate and transcutaneous tibial nerve stimulation for urinary symptoms. A number of new smaller or open trials as well as post‐hoc analyses of randomized, controlled trials have suggested usefulness of other treatments, and new randomized, controlled trials are currently ongoing. © 2015 International Parkinson and Movement Disorder Society

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“…They experience pain fluctuations during ‘ON’ and ‘OFF’ states, and can present with more than one type of pain, which increases the complexity of diagnosis and treatment (Drake et al ., ; Kim et al ., ). Pain can present before or after the diagnosis of motor symptoms and, similarly, alteration in sensory threshold testing is noted in both early‐ and late‐stage rodent models of PD (Lin et al ., ; Saade et al ., ; Chudler & Lu, ; Marques et al ., ; Zengin‐Toktas et al ., ). Optimal treatment of motor symptoms with dopaminergic medication or subthalamic nucleus (STN) deep‐brain stimulation (DBS) can provide some analgesic effects earlier in the disease process (Ciampi de Andrade et al ., ; Fil et al ., ; Marques et al ., ), but many become refractory to pain treatment as PD progresses (Benabid et al ., ; Surucu et al ., ).…”

Section: Introductionmentioning

confidence: 99%

The effects of subthalamic deep brain stimulation on mechanical and thermal thresholds in 6OHDA‐lesioned rats

Gee

Chen

Ramirez‐Zamora

et al. 2015

Eur J of Neuroscience

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Chronic pain is a major complaint for up to 85% of Parkinson Disease patients, however, often not identified as a symptom of Parkinson’s disease. Adequate treatment of motor symptoms often provides analgesic effects in Parkinson’s patients, how this occurs remains unclear. Studies have shown both Parkinson’s patients and 6-hydroxydopamine lesioned rats exhibit decreased sensory thresholds. In humans, some show improvements in these deficits after subthalamic deep brain stimulation, while others report no change. Differing methods of testing and response criteria may explain these varying results. We examined this effect in 6-hydroxydopamine lesioned rats. Sprague dawley rats were unilaterally implanted with subthalamic stimulating electrodes in the lesioned right hemisphere and sensory thresholds were tested using vonFrey, tail flick and hot plate tests. Tests were done during and off subthalamic stimulation at 50 and 150Hz to assess its effects on sensory thresholds. 6-hydroxydopamine lesioned animals exhibited lower mechanical (left paw, p<0.01) and thermal thresholds than shams (hot plate, p<0.05). Both 50 and 150Hz increased mechanical (left paw; p<0.01) and thermal thresholds in 6-hydroxydopamine lesioned rats (HPT; 150Hz, p<0.05, 50Hz, p<0.01). Interestingly, the magnitude of improvement in mechanical thresholds during LFS was similar between animals, whereas during HFS was much more diverse. This study shows that subthalamic deep brain stimulation improves mechanical allodynia and thermal hyperalgesia in 6-hydroxydopamine lesioned animals at both high and low frequencies. Furthermore, we suggest considering using low frequency stimulation when treating Parkinson’s patients where pain remains the predominant complaint.

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Central pain modulation after subthalamic nucleus stimulation

Abstract: Clinical pain alleviation after STN-DBS cannot be considered merely as a consequence of motor complications improvement and could be attributable to a direct central modulation of pain perception, via increased mechanical pain and tolerance thresholds.

Cited by 70 publications

References 38 publications

Sensory symptoms in Parkinson's disease: Clinical features, pathophysiology, and treatment

Sensory symptoms in Parkinson's disease: Clinical features, pathophysiology, and treatment

New clinical trials for nonmotor manifestations of Parkinson's disease

The effects of subthalamic deep brain stimulation on mechanical and thermal thresholds in 6OHDA‐lesioned rats

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