Extrinsic Primary Afferent Neurons Link Visceral Pain to Colon Motility Through a Spinal Reflex in Mice

Ren

Evidence-Based Complementary and Alternative Medicine

et al. 2020

Background. Sepsis is a global major health problem with high mortality rates. More effective therapy is needed for treating sepsis. Acupuncture has been used for various diseases, including severe infection, in China for more than 2,000 years. Previous studies reported that acupuncture at Zusanli (ST36) might be effective in treating sepsis, but the efficacy and the quality of evidence remain unclear since there is no systematic review on acupuncture at ST36 for sepsis. Methods. Seven databases were searched from the inception of each database up to May 2019. Ultimately, 54 studies using acupuncture at ST36 for the treatment of experimental sepsis were identified in both English and Chinese literature with systematic review procedures. Results. Acupuncture might be useful in reducing injuries induced by sepsis in cardiac, lung, kidney, liver, gastrointestinal tract, and immune system. Its potential mechanisms for antisepsis might include reducing oxidative stress and inflammation, improving microcirculatory disturbance, and maintaining the immune balance mediated by dopamine. However, the positive findings should be interpreted with caution due to poor methodological quality and publication bias. Conclusion. Acupuncture at ST36 might be a promising complementary strategy for controlling sepsis inflammation, yet further studies are needed.

Section: 1mentioning

confidence: 99%

Acupuncture at Zusanli (ST36) for Experimental Sepsis: A Systematic Review

Ren

Evidence-Based Complementary and Alternative Medicine

et al. 2020

“…This imaging technology can monitor enteric neuron development and turnover 72 , which can be a useful technique for analyzing disease models like Hirschsprung's disease, to monitor aganglionosis in the distal colon 73,74 . While in vitro and ex vivo experiments provide useful data regarding ENS dynamics 75,76 , it is more physiologically relevant to monitor the ENS in vivo in which extrinsic pathways are intact and the ENS can interact with immune cells, enteroendocrine cells, and others 49,[77][78][79][80] . Such in vivo data will be essential for modeling the ENS in silico 79 .…”

Section: Discussionmentioning

confidence: 99%

“…However, the mechanisms by which SNS affects the ENS is largely unknown. Recently, Smith-Edwards and Najjar et al demonstrated mouse colonic myenteric neurons respond to electrical stimulation of lumbosacral parasympathetic fibers under acute, non-survival conditions 49 . Here, we used our intravital imaging technique to visualize the myenteric plexus in Wnt1-tdTomato mice over several hours through the colonic window and to test our ability to visualize this population while minimizing motion artifact ( Supplementary Fig.…”

Section: Imaging Of Bacteria and Luminal Content In The Colon In Vivomentioning

confidence: 99%

See 1 more Smart Citation

An intravital window to image the colon in real time

et al. 2019

Intravital microscopy is a powerful technique to observe dynamic processes with single-cell resolution in live animals. No intravital window has been developed for imaging the colon due to its anatomic location and motility, although the colon is a key organ where the majority of microbiota reside and common diseases such as inflammatory bowel disease, functional gastrointestinal disorders, and colon cancer occur. Here we describe an intravital murine colonic window with a stabilizing ferromagnetic scaffold for chronic imaging, minimizing motion artifacts while maximizing long-term survival by preventing colonic obstruction. Using this setup, we image fluorescently-labeled stem cells, bacteria, and immune cells in live animal colons. Furthermore, we image nerve activity via calcium imaging in real time to demonstrate that electrical sacral nerve stimulation can activate colonic enteric neurons. The simple implantable apparatus enables visualization of live processes in the colon, which will open the window to a broad range of studies.

“…Besides, ExPAN stimulation initiates myenteric neuron activity and subsequent colon contractions, but only in the presence of an intact spinal cord, confirming the presence of a sensoryparasympathetic spinal circuit regulating colonic motility. The described circuit demonstrated how visceral pain is linked to colon motility and explain why pain and dysmotility co-occur in GI disorders (65). Anyway, these results complicate further the network at the base of visceral sensitivity and might preclude the possibility of achieving a selective modulation of pain.…”

Section: Peripheral Visceral Neurotransmissionmentioning

confidence: 90%

Abdominal pain models: mechanisms and therapies and experimental models

Lucarini¹,

Mannelli²,

Ghelardini³

2020

Pharm Adv

Chronic or recurrent abdominal pain is the most prevalent gastrointestinal disorder, affecting 10% of the general population, including children and adolescents. It is a common feature of both intestinal functional disorders, like irritable bowel syndrome (IBS), and inflammatory bowel diseases (IBDs). These two conditions often overlap from the clinical point of view since a large subset of IBD patients experience persistent abdominal pain even after reaching remission from the intestinal inflammation, developing a condition called IBS-like. Visceral pain management is a major clinical problem in these patients since the lack of effective and safe drugs. Despite the large number of sufferers, the mechanisms that drive the development and the persistence of chronic abdominal pain remain largely unresolved and this presents a major barrier to progress in the development of new therapies. Chronic abdominal pain often displays a complex nature with mixed nociceptive, inflammatory, emotional and neuropathic components. This is mainly attributable to the intricated regulation of visceral sensitivity which involves many actors in the gut as well as in the peripheral and central nervous systems. In this text we describe the neuroanatomical bases of visceral pain signalling, the pathophysiological mechanisms involved in pain persistence and how current treatments work, including an overview of potential new targets. In the context of drug discovery, the potential advantages and disadvantages of different preclinical models of visceral pain were also discussed.