Visceral pain is among the most prevalent and bothersome forms of chronic pain, but their transmission in the spinal cord is still poorly understood. Here, we conducted focal colorectal distention (fCRD) to drive both visceromotor responses (VMRs) and aversion. We first found that spinal CCK neurons were necessary for noxious fCRD to drive both VMRs and aversion under naive conditions. We next showed that spinal VGLUT3 neurons mediate visceral allodynia, whose ablation caused loss of aversion evoked by low-intensity fCRD in mice with gastrointestinal (GI) inflammation or spinal circuit disinhibition. Importantly, these neurons were dispensable for driving sensitized VMRs under both inflammatory and central disinhibition conditions. Anatomically, a subset of VGLUT3 neurons projected to parabrachial nuclei, whose photoactivation sufficiently generated aversion in mice with GI inflammation, without influencing VMRs. Our studies suggest the presence of different spinal substrates that transmit nociceptive versus affective dimensions of visceral sensory information.
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http://dx.doi.org/10.1016/j.neuron.2022.12.003 | DOI Listing |
Brain Res
January 2025
Department of Anatomy, Faculty of Medicine, Kansai Medical University, Shinmachi 2-5-1, Hirakata, Osaka, Japan. Electronic address:
CD34 is a well-known cell marker of hematopoietic stem/ progenitor cells, endothelial cells, and fibrocytes. In the peripheral nervous system, a certain type of primary sensory neuron C-fiber low threshold mechanoreceptors (C-LTMRs) are reported to express CD34 mRNA. Here, we investigated the distribution of CD34 protein among putative C-LTMRs (pC-LTMR) using pC-LTMR markers such as VGLUT3 and TH in the dorsal root ganglion (DRG) and spinal cord.
View Article and Find Full Text PDFNeuron
March 2023
Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address:
Visceral pain is among the most prevalent and bothersome forms of chronic pain, but their transmission in the spinal cord is still poorly understood. Here, we conducted focal colorectal distention (fCRD) to drive both visceromotor responses (VMRs) and aversion. We first found that spinal CCK neurons were necessary for noxious fCRD to drive both VMRs and aversion under naive conditions.
View Article and Find Full Text PDFEur J Pharmacol
November 2022
Robarts Research Institute, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, N6A5K8, Canada; Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, N6A5K8, Canada; Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, N6A5K8, Canada. Electronic address:
Vesicular glutamate transporters (VGLUTs) are responsible for the storage of glutamate into secretory vesicles. The VGLUT3 isoform is mainly expressed in neurons that secrete other classical neurotransmitters, including the cholinergic interneurons in the striatum, and VGLUT3-expressing neurons often secrete two distinct neurotransmitters. VGLUT3 is discretely distributed throughout the brain and is found in subpopulations of spinal cord interneurons, in subset of neurons in the dorsal root ganglion, and in Merkel cells.
View Article and Find Full Text PDFJ Neurosci
September 2020
Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery and Miami Itch Center, University of Miami Miller School of Medicine, Miami, Florida 33136
Innocuous mechanical stimuli, such as rubbing or stroking the skin, relieve itch through the activation of low-threshold mechanoreceptors. However, the mechanisms behind this inhibition remain unknown. We presently investigated whether stroking the skin reduces the responses of superficial dorsal horn neurons to pruritogens in male C57BL/6J mice.
View Article and Find Full Text PDFACS Chem Neurosci
September 2020
Instituto de Investigaciones en Medicina Traslacional (IIMT), CONICET-Austral, Derqui, Pilar B1629AHJ, Buenos Aires, Argentina.
Studies in mouse, and to a lesser extent in rat, have revealed the neuroanatomical distribution of vesicular glutamate transporters (VGLUTs) and begun exposing the critical role of VGLUT2 and VGLUT3 in pain transmission. In the present study in rat, we used specific riboprobes to characterize the transcript expression of all three VGLUTs in lumbar dorsal root ganglia (DRGs) and in the thoracolumbar, lumbar, and sacral spinal cord. We show for the first time in rat a very discrete VGLUT3 expression in DRGs and in deep layers of the dorsal horn.
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