A neuronal circuit for activating descending modulation of neuropathic pain

Huang, Junting; Gadotti, Vinícius M.; Chen, Lina; Souza, Ivana A.; Huang, Shuo; Wang, Decheng; Ramakrishnan, Charu; Deisseroth, Karl; Zhang, Zizhen; Zamponi, Gerald W.

doi:10.1038/s41593-019-0481-5

Cited by 213 publications

(284 citation statements)

References 47 publications

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“…Rozeske et al reported that specific activation of the dmPFC-l/vlPAG pathway leads to low-fear states (reducing freezing levels) during contextual fear discrimination, which was similar to our results (42). A likely possibility is that excitatory dmPFC afferents impinge upon the GAD2+ neurons in the l/vlPAG (23), and thus inhibited vlPAG-Mc neuropathway. Besides, inhibition of GAD2+ neurons through CeA inhibitory inputs during cued fear expression would lead to fear responses, as already documented (28).…”

Section: Both Gabaar and Mglur1 In The Dmpfc Are Involved In Chronic supporting

confidence: 91%

“…Huang et al recently showed the existence and the antinociceptive function of the dmPFC-vlPAG pathway. Huang et al' study used various tracers and viruses to investigate the projections from mPFC to vlPAG (23). However, the synaptic evidence was not consolidation.…”

Section: Both Gabaar and Mglur1 In The Dmpfc Are Involved In Chronic mentioning

confidence: 99%

“…Conditioned place preference scores and place escape/avoidance behavior have also been influenced by these PV-containing neurons in the PL (32). However, optogenetic either activation or deactivation of amygdala-PFC inputs did not affect anxiety behaviors in spared nerve injury (SNI) mice (23). Huang et al' study mainly focused on the analgesic effects of dmPFC-vlPAG neural pathway.…”

Section: Both Gabaar and Mglur1 In The Dmpfc Are Involved In Chronic mentioning

confidence: 99%

“…This pain-related inhibition of dmPFC neurons in the arthritic model depended on metabotropic glutamate receptor 1 (mGluR1)-mediated endogenous activation of gamma-aminobutyric acid receptor subtype A (GABAAR) (19). However, the exact neural pathway from the dmPFC involved in pain modulation has only begun to be revealed (23). The periaqueductal gray (PAG)-rostral ventromedial medulla (RVM)-spinal dorsal horn (SDH) pathway is one of the most important neural pathways involved in descending pain modulation (24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

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dmPFC-vlPAG projection neurons contribute to pain threshold maintenance and antianxiety behaviors

Yin

Liang

et al. 2020

Journal of Clinical Investigation

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The dorsal medial prefrontal cortex (dmPFC) has been recognized as a key cortical area for nociceptive modulation. However, the underlying neural pathway and the function of specific cell types remain largely unclear. Here, we showed that lesions of the dmPFC induced an algesic and anxious state. By using multiple tracing methods including rabies-based transsynaptic tracing method, an excitatory descending neural pathway from the dmPFC to the ventrolateral periaqueductal gray (vlPAG) was outlined. Specific activation of the dmPFC-vlPAG neural pathway by an optogenetic manipulation, produced analgesic and anxiolytic effects in a chronic pain mice model. Inhibitory neurons in the dmPFC were specifically activated by using a chemogenetic approach, which logically produced an algesic and anxious state under both normal and chronic pain conditions. Antagonists of GABAAR or mGluR1 were applied to the dmPFC, which produced analgesic and anxiolytic effects. In summary, the present results suggest that the dmPFC-vlPAG neural pathway might participate in the maintenance of pain thresholds and anxiolytic behaviors under normal conditions, while silencing or suppressing the dmPFC-vlPAG pathway might be involved in the initial stages and maintenance of chronic pain and the emergence of anxiety-like behaviors.

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Section: Both Gabaar and Mglur1 In The Dmpfc Are Involved In Chronic supporting

confidence: 91%

Section: Both Gabaar and Mglur1 In The Dmpfc Are Involved In Chronic mentioning

confidence: 99%

Section: Both Gabaar and Mglur1 In The Dmpfc Are Involved In Chronic mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

dmPFC-vlPAG projection neurons contribute to pain threshold maintenance and antianxiety behaviors

Yin

Liang

et al. 2020

Journal of Clinical Investigation

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“…The amygdaloid complex is well known to be relevant to fear learning, anxiety, reward, and pain (Duvarci and Pare, 2014;Li et al, 2013;Tovote et al, 2015;Tye et al, 2011;Zhuo, 2008). Even the PFC (Huang et al, 2019) and IC (Berret et al, 2019) have been reported to interact with the amygdala in processing cognition, emotion, and pain. This raises the possibility that the amygdala could be an important site for processing the depressive symptoms associated with pain (Senn et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

A Central Amygdala Input to the Parafascicular Nucleus Controls Comorbid Pain in Depression

et al. 2019

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Effects of different types of neonatal pain on somatosensory and cognitive development in male juvenile rats

Ling,

Wang,

Zheng

et al. 2023

Brain and Behavior

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BackgroundPremature infants are inevitably exposed to painful events, including repetitive procedures, inflammation, or mixed stimulation that may induce long‐term behavioral outcomes. Here, we set up three neonatal painful models to investigate their long‐term effect on somatosensation and cognition.MethodsThree types of neonatal pain models in rat were set up. Rat pups were randomly assigned to four groups. The needling pain (NP) group received repetitive needle pricks on the paws from the day of birth (PD0) to postnatal day 7 (PD7) to mimic the diagnostic and therapeutic procedures. The inflammatory pain (IP) group received the injection of carrageenan into the left hindpaw at PD3 to induce IP in peripheral tissues. The mixed pain group received a combination of the NP and IP (NIP). The control (CON) group was untreated. We performed behavioral and biochemical testing of juvenile rats (PD21–PD26).ResultsThe NIP group showed a longer hypersensitivity than the NP group, when given a secondary inflammatory stimulation. NP led to insensitivity to anxiety‐causing stimuli and impairment of fear memory both aggravated by NIP. NP reduced the expression of synapse‐related molecules (GluN1/PSD95/GFAP) in the medial prefrontal cortex, and NIP exacerbated this decrease. The corticosterone secretion in the NIP group increased after the behavioral task, compared with those in other three groups.ConclusionA combination of NP with inflammation occurring in the neonatal period might aggravate the adverse effects of each on somatosensory and cognitive development of rats, the mechanism of which might be associated with the increase of corticosterone secretion and the dysregulation of synaptic molecules.

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A neuronal circuit for activating descending modulation of neuropathic pain

Cited by 213 publications

References 47 publications

dmPFC-vlPAG projection neurons contribute to pain threshold maintenance and antianxiety behaviors

dmPFC-vlPAG projection neurons contribute to pain threshold maintenance and antianxiety behaviors

A Central Amygdala Input to the Parafascicular Nucleus Controls Comorbid Pain in Depression

Effects of different types of neonatal pain on somatosensory and cognitive development in male juvenile rats

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