Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Neuron (Cambridge, Mass.), 2023-03, Vol.111 (5), p.669-681.e5

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. •Focal colorectal distention (fCRD) can drive both visceromotor reflexes and aversion•Spinal CCK neurons drive acute visceromotor reflexes and aversion by noxious fCRD•Spinal VGLUT3 lineage neurons drive fCRD-evoked allodynia in mice with colitis•Spinal VGLUT3-negative neurons sufficiently drive sensitized visceromotor reflexes Qi et al. uncover a spinal substrate that is required to drive aversion evoked by low-intensity colorectal distension in mice with gastrointestinal inflammation, but which is dispensable for visceromotor responses, thereby calling for a revisit on how to measure the affective component of visceral pain.