Spinal VGLUT3 lineage neurons drive visceral mechanical allodynia but not visceromotor reflexes

Qi, Lu; Lin, Shing-Hong; Ma, Qiufu

doi:10.1101/2022.09.07.507044

Cited by 2 publications

(1 citation statement)

References 136 publications

(274 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activation of vGluT3 + interneurons leads to increased mechanical hypersensitivity and allodynia. vGluT3 + interneurons also play a large role in visceral (internal organ) pain processing (Brumovsky, 2013;Qi et al, 2022).…”

Section: Heterogenous Neuronal Subtypes and Neuronal Circuitry In The...mentioning

confidence: 99%

Comparison of NMDA Receptor Subunit RNA Expression in the Spinal Dorsal Horn Across Species (Mice, Rats, Humans), Sex, Laminar Location and Neuronal Subtypes using Single Cell RNA Sequencing Data and qRT-PCR

Martin

View full text Add to dashboard Cite

The hyperexcitability and central sensitization of spinal pain processing circuits is mediated by N-methyl-d-aspartate receptors (NMDARs) in the dorsal horn. Distinct circuits of neuronal subtypes in the superficial dorsal horn (SDH) versus the deep dorsal horn (DDH) primarily integrate pain and other somatosensory signals, respectively.Unique combinations of NMDAR subunits (GluN1/GRIN1, GluN2A -D/GRIN2A -D, and GluN3A -B/GRIN3A -B) confer different functional NMDAR properties and have differing effects on synaptic plasticity. In this study, we investigated NMDAR subunit expression across sex, species, spinal region, and neuronal subtypes using single cell/nucleus RNA sequencing data from the mouse and human spinal cord and performing qRT-PCR on adult male and female rat and human spinal cord tissue. We found high GRIN1, GRIN2A, GRIN2B, and GRIN3A expression and moderate GRIN2D expression in the SDH. Unlike in the rat dorsal horn, GRIN2C is highly expressed in the human dorsal horn. Both GRIN2C and GRIN2D are more highly expressed in inhibitory than excitatory neurons of the dorsal horn, but to a greater extent humans than in mice.Grin3a is more highly expressed in excitatory than inhibitory neurons of the mouse SDH.Compared to the other NMDAR subunits, GRIN2A and GRIN3A have variable expression across neuronal subtypes, but could play different roles in synaptic plasticity. Taken together, our results suggest that select NMDAR subunit genes play prominent and specialized roles in SDH somatosensory processing and different neuronal subtypes may have different patterns of GRIN gene expresssion.

show abstract

Section: Heterogenous Neuronal Subtypes and Neuronal Circuitry In The...mentioning

confidence: 99%

Comparison of NMDA Receptor Subunit RNA Expression in the Spinal Dorsal Horn Across Species (Mice, Rats, Humans), Sex, Laminar Location and Neuronal Subtypes using Single Cell RNA Sequencing Data and qRT-PCR

Martin

View full text Add to dashboard Cite

show abstract

Divergent changes in PBN excitability in a mouse model of neuropathic pain

Torruella-Suárez,

Neugebauer,

Flores-Felix

et al. 2023

Preprint

View full text Add to dashboard Cite

The transition from acute to chronic pain involves maladaptive plasticity in central nociceptive pathways. Growing evidence suggests that changes within the parabrachial nucleus (PBN), an important component of the spino-parabrachio-amygdaloid pain pathway, are key contributors to the development and maintenance of chronic pain. In animal models of chronic pain, PBN neurons become sensitive to normally innocuous stimuli and responses to noxious stimuli become amplified and more often produce after-discharges that outlast the stimulus. Using ex vivo slice electrophysiology and two mouse models of neuropathic pain, sciatic cuff and chronic constriction of the infraorbital nerve (CCI-ION), we find that changes in the firing properties of PBN neurons and a shift in inhibitory synaptic transmission may underlie this phenomenon. Compared to PBN neurons from shams, a larger proportion of PBN neurons from mice with a sciatic cuff were spontaneously active at rest, and these same neurons showed increased excitability relative to shams. In contrast, quiescent PBN neurons from cuff mice were less excitable than those from shams. Despite an increase in excitability in a subset of PBN neurons, the presence of after-discharges frequently observed in vivo were largely absent ex vivo in both injury models. However, GABAB-mediated presynaptic inhibition of GABAergic terminals is enhanced in PBN neurons after CCI-ION. These data suggest that the amplified activity of PBN neurons observed in rodent models of chronic pain arise through a combination of changes in firing properties and network excitability.

show abstract

Spinal VGLUT3 lineage neurons drive visceral mechanical allodynia but not visceromotor reflexes

Cited by 2 publications

References 136 publications

Comparison of NMDA Receptor Subunit RNA Expression in the Spinal Dorsal Horn Across Species (Mice, Rats, Humans), Sex, Laminar Location and Neuronal Subtypes using Single Cell RNA Sequencing Data and qRT-PCR

Comparison of NMDA Receptor Subunit RNA Expression in the Spinal Dorsal Horn Across Species (Mice, Rats, Humans), Sex, Laminar Location and Neuronal Subtypes using Single Cell RNA Sequencing Data and qRT-PCR

Divergent changes in PBN excitability in a mouse model of neuropathic pain

Contact Info

Product

Resources

About