Thalamic Nucleus Reuniens Glutamatergic Neurons Mediate Colorectal Visceral Pain in Mice via 5-HT2B Receptors

 Di Li1  · Han Du1  · Shu‑Ting Qu2  · Jing‑Lai Wu1  · Yong‑Chang Li1  · Qi‑Ya Xu1  · Xia Chen3  · Xiao‑Xuan Dai1  · Ji‑Tian Xu4  · Qian Wang3  · Guang‑Yin Xu1
1 Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou 215123, China 
2 Department of Gastroenterology, The First Afliated Hospital of Soochow University, Suzhou 215123, China 
3 Department of Anesthesiology, Children’s Hospital of Soochow University, Suzhou 215123, China 
4 Department of Physiology and Neurobiology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China

Irritable bowel syndrome (IBS) is a common functional bowel disorder characterized by abdominal pain and visceral hypersensitivity. Reducing visceral hypersensitivity is the key to effectively relieving abdominal pain in IBS. Increasing evidence has confirmed that the thalamic nucleus reuniens (Re) and 5-hydroxytryptamine (5-HT) neurotransmitter system play an important role in the development of colorectal visceral pain, whereas the exact mechanisms remain largely unclear. In this study, we found that high expression of the 5-HT2B receptors in the Re glutamatergic neurons promoted colorectal visceral pain. Specifically, we found that neonatal maternal deprivation (NMD) mice exhibited visceral hyperalgesia and enhanced spontaneous synaptic transmission in the Re brain region. Colorectal distension (CRD) stimulation induced a large amount of c-Fos expression in the Re brain region of NMD mice, predominantly in glutamatergic neurons. Furthermore, optogenetic manipulation of glutamatergic neuronal activity in the Re altered colorectal visceral pain responses in CON and NMD mice. In addition, we demonstrated that 5-HT2B receptor expression on the Re glutamatergic neurons was upregulated and ultimately promoted colorectal visceral pain in NMD mice. These findings suggest a critical role of the 5HT2B receptors on the Re glutamatergic neurons in the regulation of colorectal visceral pain.

Colorectal visceral pain; Thalamic nucleus reuniens; Neonatal maternal deprivation; Glutamatergic neurons; 5-HT2B receptors