Ephrin‐B2 signaling in the spinal cord as a player in post‐inflammatory and stress‐induced visceral hypersensitivity

2020 ◽  
Vol 32 (4) ◽  
Author(s):  
Stavroula A. Theofanous ◽  
Morgane V. Florens ◽  
Iris Appeltans ◽  
Alexandre Denadai Souza ◽  
John N. Wood ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Visceral Hypersensitivity

scholarly journals Study on the Mechanism Underlying the Regulation of the NMDA Receptor Pathway in Spinal Dorsal Horns of Visceral Hypersensitivity Rats by Moxibustion

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
L. D. Wang ◽  
J. M. Zhao ◽  
R. J. Huang ◽  
L. Y. Tan ◽  
Z. H. Hu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Irritable Bowel Syndrome ◽  
Visceral Pain ◽  
Intrathecal Injection ◽  
Visceral Hypersensitivity ◽  
Regulatory Function ◽  
Visceral Hyperalgesia ◽  
Spinal Dorsal ◽  
Dorsal Horns ◽  
Irritable Bowel

Visceral hypersensitivity is enhanced in irritable bowel syndrome (IBS) patients. Treatment of IBS visceral pain by moxibustion methods has a long history and rich clinical experience. In the clinic, moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints can effectively treat bowel disease with visceral pain and diarrhea symptoms. To investigate the regulatory function of moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints on spinal cord NR1, NR2B, and PKCεprotein and mRNA expression in irritable bowel syndrome (IBS) visceral hypersensitivity rats, we did some research. In the study, we found that moxibustion effectively relieved the IBS visceral hyperalgesia status of rats. Analgesic effect of moxibustion was similar to intrathecal injection of Ro 25-6981. The expression of NR1, NR2B, and PKCεin the spinal dorsal horns of IBS visceral hyperalgesia rats increased. Moxibustion on the Tianshu and Shangjuxu acupoints might inhibit the visceral hypersensitivity, simultaneously decreasing the expression of NR1, NR2B, and PKCεin spinal cord of IBS visceral hyperalgesia rats. Based on the above experimental results, we hypothesized NR1, NR2B, and PKCεof spinal cord could play an important role in moxibustion inhibiting the process of central sensitization and visceral hyperalgesia state.

scholarly journals Blockade of BK channels attenuates chronic visceral hypersensitivity in an IBS-like rat model

2021 ◽  
Vol 17 ◽  
pp. 174480692110403
Author(s):  
F Fan ◽  
Y Chen ◽  
Z Chen ◽  
L Guan ◽  
Z Ye ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nmda Receptors ◽  
Inhibitory Interneuron ◽  
Bk Channels ◽  
Bk Channel ◽  
Visceral Hypersensitivity ◽  
Potassium Ion Channels ◽  
Whole Cell Patch Clamp ◽  
Underlying Mechanisms ◽  
Irritable Bowel

Background Visceral hypersensitivity in irritable bowel syndrome (IBS) is still poorly understood, despite that chronic abdominal pain is the most common symptoms in IBS patients. To study effects of BK channels on visceral hypersensitivity in IBS rats and the underlying mechanisms, IBS rats were established by colorectal distention (CRD) in postnatal rats. The expression of large-conductance calcium and voltage-dependent potassium ion channels (BK channels) of the thoracolumbar spinal cord was examined in IBS and control rats. The effects of BK channel blockade on visceral hypersensitivity were evaluated. The interaction of BK channels and N-methyl-D-aspartate acid (NMDA) receptors was explored, and synaptic transmission at superficial dorsal horn (SDH) neurons of the thoracolumbar spinal cord was recorded by whole-cell patch clamp in IBS rats. Results The expression of the BK channels of the thoracolumbar spinal cord in IBS rats was significantly reduced. The blockade of BK channels could reduce the visceral hypersensitivity in IBS rats. There was an interaction between BK channels and NMDA receptors in the spinal cord. The frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in SDH neurons is significantly reduced in IBS rats. The blockade of BK channels depolarizes the inhibitory interneuron membrane and increases their excitability in IBS rats. Conclusions BK channels could interact with NMDA receptors in the thoracolumbar spinal cord of rats and regulate visceral hypersensitivity in IBS rats.

scholarly journals Targeting spinal TRAF6 expression attenuates chronic visceral pain in adult rats with neonatal colonic inflammation

2020 ◽  
Vol 16 ◽  
pp. 174480692091805 ◽  
Author(s):  
Rui-Xia Weng ◽  
Wei Chen ◽  
Jia-Ni Tang ◽  
Qian Sun ◽  
Meng Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Irritable Bowel Syndrome ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Visceral Pain ◽  
Intrathecal Injection ◽  
Visceral Hypersensitivity ◽  
Colonic Inflammation ◽  
Spinal Dorsal ◽  
Irritable Bowel

Background Irritable bowel syndrome is one of the most common gastrointestinal disorders. It is featured by abdominal pain in conjunction with altered bowel habits. However, the pathophysiology of the syndrome remains largely unknown. Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been reported to be involved in neuropathic pain. The aim of this study was to investigate roles and mechanisms of TRAF6 in the chronic visceral hypersensitivity. Methods Visceral hypersensitivity was induced by neonatal colonic inflammation and was identified by colorectal distention. The protein level, RNA level, and cellular distribution of TRAF6 and its related molecules were detected with Western blot, quantitative polymerase chain reaction, and immunofluorescence. In vitro spinal cord slice recording technique was performed to determine the synaptic transmission activities. Results Neonatal colonic inflammation rats displayed visceral hypersensitivity at the age of six weeks. The expression of TRAF6 was obviously upregulated in spinal cord dorsal horn of neonatal colonic inflammation rats at the age of six weeks. Immunofluorescence study showed that TRAF6 was dominantly expressed in spinal astrocytes. Intrathecal injection of TRAF6 small interfering RNA (siRNA) significantly reduced the amplitude of spontaneous excitatory postsynaptic currents at the spinal dorsal horn level. Furthermore, knockdown of TRAF6 led to a significant downregulation of cystathionine β synthetase expression in the spinal dorsal horn of neonatal colonic inflammation rats. Importantly, intrathecal injection of TRAF6 siRNA remarkably alleviated visceral hypersensitivity of neonatal colonic inflammation rats. Conclusions Our results suggested that the upregulation of TRAF6 contributed to visceral pain hypersensitivity, which is likely mediated by regulating cystathionine β synthetase expression in the spinal dorsal horn. Our findings suggest that TRAF6 might act as a potential target for the treatment of chronic visceral pain in irritable bowel syndrome patients.

Role of the potassium chloride cotransporter isoform 2-mediated spinal chloride homeostasis in a rat model of visceral hypersensitivity

2015 ◽  
Vol 308 (9) ◽  
pp. G767-G778 ◽  
Author(s):  
Dong Tang ◽  
Ai-Hua Qian ◽  
Dan-Dan Song ◽  
Qi-Wen Ben ◽  
Wei-Yan Yao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Chronic Stress ◽  
Intrathecal Injection ◽  
Visceral Hypersensitivity ◽  
Equilibrium Potential ◽  
Lumbosacral Spinal Cord ◽  
Lamina I ◽  
Male Wistar Rats ◽  
Adult Spinal Cord ◽  
And Function

Visceral hypersensitivity represents an important hallmark in the pathophysiology of irritable bowel syndrome (IBS), of which the mechanisms remain elusive. The present study was designed to examine whether cation-chloride cotransporter (CCC)-mediated chloride (Cl−) homeostasis of the spinal cord is involved in chronic stress-induced visceral hypersensitivity. Chronic visceral hypersensitivity was induced by exposing male Wistar rats to water avoidance stress (WAS). RT-PCR, Western blotting, and immunohistochemistry were used to assess the expression of CCCs in the spinal cord. Patch-clamp recordings were performed on adult spinal cord slices to evaluate Cl− homeostasis and Cl− extrusion capacity of lamina I neurons. Visceral sensitivity was estimated by measuring the abdominal withdrawal reflex in response to colorectal distension (CRD). After 10 days of WAS exposure, levels of both total protein and the oligomeric form of the K+-Cl− cotransporter isoform 2 (KCC2), but not Na+-K+-2Cl− transporter isoform 1 (NKCC1), were significantly decreased in the dorsal horn of the lumbosacral spinal cord. The downregulation of KCC2 resulted in a depolarizing shifted equilibrium potential of GABAergic inhibitory postsynaptic current and impaired Cl− extrusion capacity in lamina I neurons of the lumbosacral spinal cord from WAS rats. Acute noxious CRD disrupted spinal KCC2 expression and function 2 h after the final distention in sham rats, but not in WAS rats. Pharmacological blockade of KCC2 activity by intrathecal injection of a KCC2 inhibitor [(dihydroindenyl)oxy] alkanoic acid enhanced visceral nociceptive sensitivity in sham rats, but not in WAS rats. These results suggest that KCC2 downregulation-mediated impairment of spinal cord Cl− homeostasis may play an important role in chronic stress-induced visceral hypersensitivity.

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