A paraventricular hypothalamic nucleus input to ventral of lateral septal nucleus controls chronic visceral pain

Li, Yongchang; Wang, Qian; Li, Mengge; Hu, Shu‐Fen; Xu, Guang–Yin

doi:10.1097/j.pain.0000000000002750

Cited by 16 publications

(15 citation statements)

References 49 publications

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“…Given its location and connections, the lateral septal nucleus forms a critical part of the limbic system, integrating a variety of emotional and cognitive information to regulate behavioral responses, reward, feeding, anxiety, fear, and sociability ( Rizzi-Wise and Wang 2021 ). It is therefore not surprising that it also has a role in pain, with the circuit from the paraventricular hypothalamus to the lateral septal region being identified as necessary and sufficient for regulating visceral pain ( Li et al. 2022 ).…”

Section: Discussionmentioning

confidence: 99%

The waiting game: investigating the neurobiological transition from acute to persistent pain in adolescent rats

et al. 2023

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Persistent postsurgical pain affects 20% of youth undergoing a surgical procedure, with females exhibiting increased prevalence of chronic pain compared with males. This study sought to examine the sexually-dimorphic neurobiological changes underlying the transition from acute to persistent pain following surgery in adolescence. Male and female Sprague Dawley rats were randomly allocated to a sham or injury (plantar-incision surgery) condition and assessed for pain sensitivity while also undergoing magnetic resonance imaging at both an acute and chronic timepoint within adolescence. We found that injury resulted in persistent pain in both sexes, with females displaying most significant sensitivity. Injury resulted in significant gray matter density increases in brain areas including the cerebellum, caudate putamen/insula, and amygdala and decreases in the hippocampus, hypothalamus, nucleus accumbens, and lateral septal nucleus. Gray matter density changes in the hippocampus and lateral septal nucleus were driven by male rats whereas changes in the amygdala and caudate putamen/insula were driven by female rats. Overall, our results indicate persistent behavioral and neurobiological changes following surgery in adolescence, with sexually-dimorphic and age-specific outcomes, highlighting the importance of studying both sexes and adolescents, rather than extrapolating from male adult literature.

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Section: Discussionmentioning

confidence: 99%

The waiting game: investigating the neurobiological transition from acute to persistent pain in adolescent rats

et al. 2023

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“…For example, neural circuits formed by glutamatergic neurons with other glutamatergic neurons modulate sleep–wake cycles, cognitive impairments, and learning and memory deficits 41–43 . In addition, our research has previously shown that other brain circuits glutamatergic neurons form neural circuits with glutamatergic neurons that modulate visceral pain 27,44 . In this study, viral tracing results revealed that excitatory neurons in the PVT projected to the IC excitatory neurons.…”

Section: Discussionmentioning

confidence: 52%

“…Fiber photometry is widely used to detect and record neuronal calcium activity based on fluorescent calcium indicator. GCaMP has an exceptionally high sensitivity to calcium ions and thus effectively indicates changes in calcium activity through instantaneous changes in fluorescence signal intensity 25–27 . To assess the calcium ion activity of glutamatergic neurons in the IC, at the sixth week after birth, AAV2/9‐vglut2‐GCaMP6s (BrainVTA, Wuhan, China) virus was injected into the IC region of both NCI and CON group mice (150 nL per injection).…”

Section: Methodsmentioning

confidence: 99%

Paraventricular thalamus‐insular cortex circuit mediates colorectal visceral pain induced by neonatal colonic inflammation in mice

Zhang,

Wei,

Weng

et al. 2023

CNS Neurosci Ther

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AimsIrritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, but its pathogenesis remains incompletely understood, particularly the involvements of central nervous system sensitization in colorectal visceral pain. Our study was to investigate whether the paraventricular thalamus (PVT) projected to the insular cortex (IC) to regulate colorectal visceral pain in neonatal colonic inflammation (NCI) mice and underlying mechanisms.MethodsWe applied optogenetic, chemogenetic, or pharmacological approaches to manipulate the glutamatergicPVT‐IC pathway. Fiber photometry was used to assess neuronal activity. Electromyography activities in response to colorectal distension (CRD) were measured to evaluate the colorectal visceral pain.ResultsNCI enhanced c‐Fos expression and calcium activity upon CRD in the ICGlu, and optogenetic manipulation of them altered colorectal visceral pain responses accordingly. Viral tracing indicated that the PVTGlu projected to the ICGlu. Optogenetic manipulation of PVTGlu changed colorectal visceral pain responses. Furthermore, selective optogenetic modulation of PVT projections in the IC influenced colorectal visceral pain, which was reversed by chemogenetic manipulation of downstream ICGlu.ConclusionsThis study identified a novel PVT‐IC neural circuit playing a critical role in colorectal visceral pain in a mouse model of IBS.

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“…The population of glutamatergic neurons in VTA is reported to be less than other types of neurons like GABA and DA, and we only wanted these glutamatergic projections to be NAc-specific rather than VTA glutamatergic projection to other brain regions in VGluT2-Cre mice. We used the CaMKII tracing method in the wild-type mice because CaMKII was reported to colonize predominantly with the glutamate neurons ( Zhu et al, 2014 ; Basting et al, 2018 ; Liu et al, 2020 ; Sheng et al, 2020 ; Zhang et al, 2020 ; Li et al, 2022 ). For this, a retrograde CaMKIIa-CRE viral vector was injected into the NAc, and DIO-EYFP was injected in the VTA of the wild-type mice ( Figure 1F ).…”

Section: Resultsmentioning

confidence: 99%

VTA-NAc glutaminergic projection involves in the regulation of pain and pain-related anxiety

Mannan

Yan

Zhao

et al. 2022

Front. Mol. Neurosci.

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BackgroundBesides the established role of dopamine neurons and projections in nociceptive stimuli, the involvement of ventral tegmental area (VTA) glutamatergic projections to nucleus accumbens (NAc) in pain remains unknown. In the present study, we aimed to examine the role of VTA glutamatergic projections to NAc in painful stimuli and its related behavioral changes.MethodsUnilateral chronic constrictive injury (CCI) of sciatic nerve or intraplantar hind paw injections (i.pl.) of complete Freund’s adjuvant (CFA) were used to develop pathological pain models in wild-type and VGluT2-Cre mice. The involvement of VTA glutamatergic neurons with projections to NAc in CCI-induced pain model was noted by c-Fos labeling and firing rate recordings. Pain response and pain-related behavior changes to the artificial manipulation of the VTA glutamatergic projections to NAc were observed by Hargreaves tests, von Frey tests, open field tests, elevated maze tests, and sucrose preference tests.ResultsGlutamatergic neurons in VTA had efferent inputs to shell area of the NAc. The CCI pain model significantly increased neuronal activity and firing rate in VTA glutamate neurons with projections to NAc. The photoinhibition of these glutamatergic projections relieved CCI-induced neuropathic pain and CFA-induced acute and chronic inflammatory pain. Moreover, pathological neuropathic pain-induced anxiety and less sucrose preference were also relieved by inhibiting the VTA glutamatergic projections to NAc.ConclusionTogether, glutamatergic inputs from VTA to NAc contribute to chronic neuropathic and inflammatory pain and pain-related anxiety and depressive behaviors, providing a mechanism for developing novel therapeutic methods.

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A paraventricular hypothalamic nucleus input to ventral of lateral septal nucleus controls chronic visceral pain

Abstract: Supplemental Digital Content is Available in the Text. Paraventricular hypothalamic CaMKIIα-positive neurons input to ventral of lateral septal CaMKIIα-positive neurons controls chronic visceral pain.

Cited by 16 publications

References 49 publications

The waiting game: investigating the neurobiological transition from acute to persistent pain in adolescent rats

The waiting game: investigating the neurobiological transition from acute to persistent pain in adolescent rats

Paraventricular thalamus‐insular cortex circuit mediates colorectal visceral pain induced by neonatal colonic inflammation in mice

VTA-NAc glutaminergic projection involves in the regulation of pain and pain-related anxiety

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