Parabrachial nucleus circuit governs neuropathic pain-like behavior

Sun, Li; Li, Rui; Guo, Fang; Wen, Man-Qing; Ma, Xiaolin; Li, Kaiyuan; Sun, Hao; Xu, Cenglin; Li, Yuanyuan; Wu, Mengyin; Zhu, Zhenggang; Li, Xinjian; Yu, Yan-Qin; Chen, Zhong; Li, Xiang-Yao; Duan, Shumin

doi:10.1038/s41467-020-19767-w

Cited by 104 publications

(127 citation statements)

References 87 publications

(147 reference statements)

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“…Crucially, the SPZ has also recently been shown to send projections to the lateral parabrachial (LPB) nucleus in the midbrain (Vujovic et al, 2015). The LPB has been extensively shown to play a vital role in the relay of pain-related information from the spinal cord to the forebrain, and through these connections the LPB appears to mediate emotional and learningbased aspects of pain (Chiang et al, 2020;Sun et al, 2020). As we will elaborate on in this review, the SCN → SPZ → LPB pathway may serve as a circuit substrate through which the circadian system could exert its influence and lead to the reported temporal differences in pain perception and sensitivity across the 24h day.…”

Section: Circadian Rhythmicitymentioning

confidence: 99%

“…Neuropathic pain and capsaicin pain both can be attenuated following either optogenetic or chemogenetic inhibition (Chiang et al, 2020;Sun et al, 2020). Additionally, driving LPB glutamatergic neurons leads to a neuropathic pain phenotype without the need of injury, but in the case of injury, such neuropathic pain can be halted by stimulating GABAergic neurons in the LPB.…”

Section: Disinhibitionmentioning

confidence: 99%

“…Importantly, when these cells are stimulated once a day for 7 days their effects become chronic, such that persistent stimulation of LPB glutamatergic neurons leads to neuropathic pain that is sustained for at least a month after any exogenous stimulation and this can be transiently inhibited by optogenetic stimulation of LPB GABAergic neurons. Additionally, when GABAergic neurons in the LPB are stimulated for the first 7 days of common peroneal nerve ligation, they can completely stop the development of neuropathic pain (Sun et al, 2020). This is achieved through a monosynaptic connection of LPB inhibitory neurons onto LPB excitatory neurons.…”

Section: Disinhibitionmentioning

confidence: 99%

“…stops are subject to circadian-mediated gain in excitation and disinhibition, which could be transmitted along the entire circuit. Indeed, central sensitization as seen in the spinal cord, following nerve ligation, has been shown in the LPB to be able to drive both physical and affective components of pain (Sun et al, 2020). Importantly, the maintenance of chronicity is also mediated by glial cells that contribute heavily to the neuroinflammation that maintains pain long after any potential tissue damage.…”

Section: Disinhibitionmentioning

confidence: 99%

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Systems and Circuits Linking Chronic Pain and Circadian Rhythms

2021

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Research over the last 20 years regarding the link between circadian rhythms and chronic pain pathology has suggested interconnected mechanisms that are not fully understood. Strong evidence for a bidirectional relationship between circadian function and pain has been revealed through inflammatory and immune studies as well as neuropathic ones. However, one limitation of many of these studies is a focus on only a few molecules or cell types, often within only one region of the brain or spinal cord, rather than systems-level interactions. To address this, our review will examine the circadian system as a whole, from the intracellular genetic machinery that controls its timing mechanism to its input and output circuits, and how chronic pain, whether inflammatory or neuropathic, may mediate or be driven by changes in these processes. We will investigate how rhythms of circadian clock gene expression and behavior, immune cells, cytokines, chemokines, intracellular signaling, and glial cells affect and are affected by chronic pain in animal models and human pathologies. We will also discuss key areas in both circadian rhythms and chronic pain that are sexually dimorphic. Understanding the overlapping mechanisms and complex interplay between pain and circadian mediators, the various nuclei they affect, and how they differ between sexes, will be crucial to move forward in developing treatments for chronic pain and for determining how and when they will achieve their maximum efficacy.

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Section: Circadian Rhythmicitymentioning

confidence: 99%

Section: Disinhibitionmentioning

confidence: 99%

Section: Disinhibitionmentioning

confidence: 99%

Section: Disinhibitionmentioning

confidence: 99%

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Systems and Circuits Linking Chronic Pain and Circadian Rhythms

2021

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“…Although activation of the PBN-PVT pathway induced significant anxiety-like behavior, it did not affect the depressive-like behaviors evaluated by the tail suspension test (TST, Figure3−figure supplement 3A) and the forced swimming test (FST, Figure3−figure supplement 3B). Previous studies have revealed that the PBN receives direct projections from the spinal cord and plays a vital role in pain processing (Deng et al, 2020;Sun et al, 2020). We then assessed whether pharmacogenetic activation of the PVT-projecting PBN neurons affects the nociceptive behaviors.…”

Section: Pharmacogenetics Activation Of the Pvt-projecting Pbn Neurons Induces Anxiety-like Behaviors And Freezing Behaviorsmentioning

confidence: 99%

PBN-PVT projection modulates negative affective states in mice

Zhu

Zhang

Wang

et al. 2021

Preprint

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Negative emotions can be described as feelings that cause us to be miserable and sad. Long-lasting negative emotions dampen enthusiasm for life; thus, dealing with negative emotions is essential for individual survival. The parabrachial nucleus (PBN) and the thalamic paraventricular nucleus (PVT) are critical for modulating affections in mice. However, the functional role of the projection from the PBN to the PVT in affection modulation remains elusive. Here, we show that the PBN neurons send dense projection fibers to the PVT and form direct excitatory synapses with the PVT neurons. Activation of the PBN-PVT projections or PVT-projecting PBN neurons induces robust anxiety-like and fear-like behaviors without affecting depression-like and nociceptive behaviors. Inhibition of the PVT-projecting PBN neurons relieves fear-like and aversion-like behaviors. Furthermore, the PVT neurons innervated by the PBN were activated in negative experiences, and activation of these neurons induced anxiety-like behavior. Thus, our study indicates that the PBN-PVT projection modulates negative emotions in mice.

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Role of autonomic, nociceptive, and limbic brainstem nuclei in core autism features

Travers,

Surgent,

Guerrero‐Gonzalez

et al. 2024

Autism Research

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Although multiple theories have speculated about the brainstem reticular formation's involvement in autistic behaviors, the in vivo imaging of brainstem nuclei needed to test these theories has proven technologically challenging. Using methods to improve brainstem imaging in children, this study set out to elucidate the role of the autonomic, nociceptive, and limbic brainstem nuclei in the autism features of 145 children (74 autistic children, 6.0–10.9 years). Participants completed an assessment of core autism features and diffusion‐ and T1‐weighted imaging optimized to improve brainstem images. After data reduction via principal component analysis, correlational analyses examined associations among autism features and the microstructural properties of brainstem clusters. Independent replication was performed in 43 adolescents (24 autistic, 13.0–17.9 years). We found specific nuclei, most robustly the parvicellular reticular formation‐alpha (PCRtA) and to a lesser degree the lateral parabrachial nucleus (LPB) and ventral tegmental parabrachial pigmented complex (VTA‐PBP), to be associated with autism features. The PCRtA and some of the LPB associations were independently found in the replication sample, but the VTA‐PBP associations were not. Consistent with theoretical perspectives, the findings suggest that individual differences in pontine reticular formation nuclei contribute to the prominence of autistic features. Specifically, the PCRtA, a nucleus involved in mastication, digestion, and cardio‐respiration in animal models, was associated with social communication in children, while the LPB, a pain‐network nucleus, was associated with repetitive behaviors. These findings highlight the contributions of key autonomic brainstem nuclei to the expression of core autism features.

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Parabrachial nucleus circuit governs neuropathic pain-like behavior

Cited by 104 publications

References 87 publications

Systems and Circuits Linking Chronic Pain and Circadian Rhythms

Systems and Circuits Linking Chronic Pain and Circadian Rhythms

PBN-PVT projection modulates negative affective states in mice

Role of autonomic, nociceptive, and limbic brainstem nuclei in core autism features

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