Revealing a novel nociceptive network that links the subthalamic nucleus to pain processing

Pautrat, Arnaud; Rolland, Marta; Barthelemy, Margaux; Baunez, Christelle; Sinniger, Valérie; Piallat, Brigitte; Savasta, Marc; Overton, Paul G.; David, Olivier; Coizet, Véronique

doi:10.7554/elife.36607

Cited by 33 publications

(54 citation statements)

References 82 publications

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“…Although recent evidences revealed the role of STN in neuronal pain processing, 21 the resistance to 94 the foot-shock induced by the STN 8 Hz stimulation did not reflect changes in pain perception, since 95 such treatment (6 h/day, 14 days) of 'shock-sensitive' animals did not affect nociceptive responses on 96 a hot-plate (Extended data Fig. 5).…”

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confidence: 90%

Low frequency oscillatory activity of the subthalamic nucleus is a predictive biomarker of compulsive-like cocaine seeking

Degoulet¹,

Tiran-Cappello²,

Baunez³

et al. 2018

Preprint

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Low frequency oscillatory activity of the subthalamic nucleus is a 1 predictive biomarker of compulsive-like cocaine seeking. 2 3 Subthalamic nucleus activity predicts compulsivity. 4 5 Abstract 16 Cocaine seeking despite a foot-shock contingency is used to model compulsive drug 17 seeking, a core component of drug addiction, in rodents. Deep brain stimulation (DBS) of 18 the subthalamic nucleus (STN) is efficient on other addiction criteria models and we show 19here that 30-Hz STN stimulation reduces pathological cocaine seeking in compulsive-like 20 rats. This confirms STN DBS as a potential strategy to treat addiction. We also observed 21 that only 'compulsive-like' rats displayed a progressive increase in STN low frequency 22 oscillations, especially in the alpha/theta band (6-13 Hz), during cocaine escalation. 23 Conversely, applying 8-Hz STN DBS to mimic alpha/theta oscillations in 'non-24 compulsive' animals changed them into 'compulsive' ones. We have thus identified a 25 predictive neuronal biomarker of compulsivity. Since one critical challenge in addiction 26 research is to identify vulnerable individuals before they transition to harmful drug 27 consumption pattern, our results could lead to new diagnostic tools and prevention 28 strategies. 29 30

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mentioning

confidence: 90%

Low frequency oscillatory activity of the subthalamic nucleus is a predictive biomarker of compulsive-like cocaine seeking

Degoulet¹,

Tiran-Cappello²,

Baunez³

et al. 2018

Preprint

Self Cite

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“…Considering that STN neurons respond to nociceptive stimuli (27,35), and that STN DBS effectively relieves pain symptoms in some PD patients (28,30,32), we wondered whether the hyperactivity in STN neurons contributes to pain hypersensitivity in parkinsonian mice. To investigate this, we injected adenoassociated virus (AAV)-CaMKII-NpHR3.0-eYFP into the STN (Fig.…”

Section: Unilateral Lesion Of Snc Da Neurons Leads To Mechanical and mentioning

confidence: 99%

“…Although abnormal activity in the STN plays a critical role in parkinsonian motor deficits (16,26), its association with pain symptoms in PD has not been well studied. An in vivo electrophysiological study revealed that STN neurons have faster spontaneous firing and stronger responses to nociceptive stimuli in parkinsonian rats compared with control rats (27). Deep brain stimulation (DBS) in patients with PD effectively relieves musculoskeletal and dystonic pain, but not central or neuropathic pain (28)(29)(30)(31)(32).…”

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confidence: 99%

Reversal of hyperactive subthalamic circuits differentially mitigates pain hypersensitivity phenotypes in parkinsonian mice

Luan

Tang

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Although pain is a prevalent nonmotor symptom in Parkinson’s disease (PD), it is undertreated, in part because of our limited understanding of the underlying mechanisms. Considering that the basal ganglia are implicated in pain sensation, and that their synaptic outputs are controlled by the subthalamic nucleus (STN), we hypothesized that the STN might play a critical role in parkinsonian pain hypersensitivity. To test this hypothesis, we established a unilateral parkinsonian mouse model with moderate lesions of dopaminergic neurons in the substantia nigra. The mice displayed pain hypersensitivity and neuronal hyperactivity in the ipsilesional STN and in central pain-processing nuclei. Optogenetic inhibition of STN neurons reversed pain hypersensitivity phenotypes in parkinsonian mice, while hyperactivity in the STN was sufficient to induce pain hypersensitivity in control mice. We further demonstrated that the STN differentially regulates thermal and mechanical pain thresholds through its projections to the substantia nigra pars reticulata (SNr) and the internal segment of the globus pallidus (GPi)/ventral pallidum (VP), respectively. Interestingly, optogenetic inhibition of STN-GPi/STN-VP and STN-SNr projections differentially elevated mechanical and thermal pain thresholds in parkinsonian mice. In summary, our results support the hypothesis that the STN and its divergent projections play critical roles in modulating pain processing under both physiological and parkinsonian conditions, and suggest that inhibition of individual STN projections may be a therapeutic strategy to relieve distinct pain phenotypes in PD.

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“…3A). Interestingly, these areas are known to either relay aversive sensory signals or integrate sensory information with emotional valence [19][20][21][22] . We also investigated downstream brain areas that receive direct input from the PBL Oprm1 neurons by stereotaxic injection of recombinant AAV that express ChR2:eYFP in a Cre-dependent manner (AAV-DIO-ChR2:eYFP), which is expressed in the cell body and axon terminals ( Fig.…”

Section: Input/output Pathways Of Pbl Oprm1 Neuronsmentioning

confidence: 99%

Identification of a novel breathing circuit that controls pain and anxiety

et al. 2020

Preprint

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Alleviating pain with controlled breathing has been practiced throughout human history. Despite its wide use and long history, a neural circuit-based understanding of the pain-breathing interaction is largely lacking.Here we report a novel breathing circuit that regulates non-homeostatic breathing rhythm, as well as pain and anxiety. We identify that a cluster of neurons expressing the Oprm1 gene, which encodes the µ-opioid receptor (MOR) in the lateral subdivision of parabrachial nucleus (PBL Oprm1 ), directly regulates breathing rate in mice by conveying signals from the limbic areas to respiratory rhythm generating neurons in the medullary preBötzinger Complex (preBötC). In addition, we found that pain signals rapidly increase breathing rate by activating these neurons in both awake and anesthetized mice. Inactivating these neurons not only decreases the breathing rate, but it also substantially decreases anxiety-like behaviors and induces strong appetitive behaviors. Furthermore, PBL Oprm1 inactivation alleviates pain by attenuating the perception of the affective-motivational aspect of pain. These results suggest that PBL Oprm1 neurons play a critical role in the non-homeostatic regulation of breathing and in the regulation of pain and anxiety through breathing.

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Revealing a novel nociceptive network that links the subthalamic nucleus to pain processing

Cited by 33 publications

References 82 publications

Low frequency oscillatory activity of the subthalamic nucleus is a predictive biomarker of compulsive-like cocaine seeking

Low frequency oscillatory activity of the subthalamic nucleus is a predictive biomarker of compulsive-like cocaine seeking

Reversal of hyperactive subthalamic circuits differentially mitigates pain hypersensitivity phenotypes in parkinsonian mice

Identification of a novel breathing circuit that controls pain and anxiety

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