He Enteric nervous system , Which is directly responsible for the digestive system, is perhaps the most unknown structure of the human body. The reason is that until now has been underestimated its importance, being less relevant than others more recognized as the central nervous system, peripheral system, endocrine system or immune system.
That is why we then go into the depths of this system, to discover its mysterious nooks and crannies inside one of the most important organs, the intestine.
The gastrointestinal tract differs from all other peripheral organs in that it has an extensive intrinsic nervous system called" Enteric Nervous System "(SNE) that can control bowel functions, even independently of the Central Nervous System (CNS).
The SNE is composed of small clusters of nerve cells, enteric ganglia, neuronal connections between these nodes and nerve fibers that supply effector tissues, including the muscle of the gut wall, epithelial lining, intrinsic blood vessels and gastroenteropancreatic endocrine cells ( Furness, 2012).
These thousands of small lymph nodes are found inside the walls of the esophagus, stomach, small and large intestine, pancreas, gallbladder and biliary tract. Also in the nerve fibers that connect these ganglia and in the nerve fibers that supply the muscle of the wall of the intestine, the epithelium of the mucosa, arterioles and other effector tissues. ( Furness, et al. 2012).
As we see, the SNE is the largest and most complex division of Peripheral nervous systems Y autonomous (SNP and SNA) in vertebrates. After the brain , Is the system that has the highest number of comparable neurons even to those found in the spinal cord , Hence it is known as the Second brain .
The SNE contains Intrinsic sensory neurons (Afferent primary intrinsic neurons, IPANs), Interneurons Y Motor neurons , Both excitatory and inhibitory, that innervate the muscle (Furness, 2012).
In addition, it also presents a variety of Neurotransmitters and neuromodulators Similar to those found in the central nervous system (CNS) (Romero-Trujillo, 2012).
For example, Serotonin (5-HT) cells that contain endocrine cells activate the reflexes of motility. Excessive serotonin release can cause nausea and vomiting, and 5-HT3 receptor antagonists are anti-nausea. Other neurotransmitters that have a role in this second brain are:
- Nitric oxide : Important for gastric emptying.
- Adenosine triphosphate (ATP) : Facilitates the effect of Catecholamines .
- Neuropeptide Y (NYP) : Facilitates the effect of Noradrenaline .
- Gamma-amino butyric acid (GABA) : An important neurotransmitter inhibitor of the central nervous system.
- Dopamine : Possible mediation of renal vasodilation.
- Releasing hormone Gonadotropin : Cotransmitter with acetylcholine in the sympathetic ganglia.
- Substance P : Intervenes in the reflex of the vomit, secretion of the saliva or contraction of the smooth muscle.
Organization of the enteric nervous system
The SNE is organized in an interconnected network of neurons and Glial cells Which are grouped into the ganglia located in two main plexuses: the myenteric plexus (or Auerbach plexus) and the submucosal plexus (or Meissner plexus) (Sasselli, 2012).
- He Submucous plexus (Meissner) is located between the inner layer of the circular muscular layer and the submucosa. It is more developed in the small intestine and colon. Its main function is the regulation of digestion and absorption at the level of the mucosa and blood vessels (Romero-Trujillo, 2012).
- He Mystolic plexus (Auerbach), is located between the circular and longitudinal muscular layers, along the entire digestive tract. Its main function is the coordination of the activity of these muscular layers (Romero-Trujillo, 2012).
Development of the SNE
The SNE originates from cells of the Neural crest Which colonize the intestine during intrauterine life. It becomes functional in the last third of gestation in humans, and continues to develop after birth.
These neural crest cells migrate from rostral to caudal to colonize sequentially the anterior (esophagus, stomach, duodenum), middle intestine (small intestine, cecum, ascending colon, appendix and proximal segment Of the transverse colon) and the posterior intestine (distal portion of the transverse colon, sigmoid, descending colon and rectum). This process is completed at seven weeks gestation in humans.
To form mature and functional nerve cells that come from the neural crest, they must migrate not only across the entire gut path, but must proliferate and differentiate into a wide range of neuronal variants and glial cells as well as achieve survival and become Active and functional cells (Romero-Trujillo, 2012).
Functions
The components of the SNE form an integrated circuit that controls a number of functions such as bowel motility, exchange of fluid across the surface of the mucosa, blood flow and secretion of intestinal hormones, among others.
Although this system has been included as within the autonomic nervous system (SNA), the intrinsic neural circuits of the SNE are able to generate the activity of the intestinal contractile reflex independently of any CNS intervention (Sasselli, 2012).
According to Furness et al. (2012), the SNE therefore has multiple functions that are listed below:
- Determining movement patterns of the gastrointestinal tract: The SNE dominates the control of small and large intestinal motility, with the exception of defecation, of which the CNS is in control through the defecation centers in the spinal cord Lumbosacral.
The small intestine, however, is dependent on the SNE to direct its different patterns of movement. In addition, rapid orthographic propulsion of contents (peristalsis), mixing movements (segmentation), slow orthogonal propulsion and retropulsion (expulsion of harmful substances through vomiting), among others, are carried out by this system. (Furness, 2012)
- It is responsible for the control of the secretion of Gastric acid .
- It regulates the flow of fluid through the lining epithelium of the intestine.
- It exerts its control by changing the local blood flow.
- Modifies the use of nutrients.
- Interacts with the intestinal immune and endocrine systems. Important point that is developed next.
- It contributes, along with glial cells, to maintaining the integrity of the epithelial barrier between the lumen of the intestine and the cells and tissues within the intestinal wall (Furness, 2012).
Enteric Nervous System Interaction (SNE) - Central Nervous System (CNS) - Immune System (SI) - Endocrine System (SE)
Although the SNE is known to be a complex system of neurons and supporting cells capable of generating information, integrating it and producing a response independently, it is not incommunicado with the rest of the body, as there is no organ, Connections with the CNS, creating afferent and efferent responses and exchanging information between the two systems.
The afferent neurons send information of three types to the CNS: the intraluminal chemical content, the mechanical state of the intestinal wall (tension or relaxation) and the condition in which the tissues are (inflammation, ph, cold, heat) (Romero. Trujillo, 2012).
The gastrointestinal tract, therefore, is in communication through two routes with the CNS:
- Through Afferent neurons Which transmit information about the state of the gastrointestinal tract to the CNS. Some of this information comes to consciousness and thanks to this communication we perceive numerous sensations including pain and discomfort in the intestine or conscious feelings of hunger and satiety.
However, other afferent signals, such as the burden of nutrients in the small intestine or the acidity of the stomach, usually do not reach consciousness.
- In turn, the CNS provides signals to control the bowel, which are, in most cases, retransmitted through the SNE through Efferent communication From the CNS to the gastrointestinal system.
For example, the sight and smell of food causes preparatory responses in the gastrointestinal tract, including salivation and gastric acid secretion. At the other end of the intestine, signals from the colon and rectum are relayed to the defecation centers in the spinal cord, which carries a programmed set of signals to the colon, rectum, and anal sphincter to cause defecation .
But the SNE not only interacts with the CNS but also interacts with the CNS. Immune system (SI) , So that SI affects gastrointestinal motility.
Communication between the two systems modulates numerous intestinal functions: motility, ionic transport and mucosal permeability.
This relationship between SNE and SI is fascinating since it has been known for some time that certain factors cause an alteration of the intestinal mucosa, which in turn leads to immune responses that lead to chronic inflammation.
Moreover, in the intestine lies no less than 70-80% of the immune system, so it is not surprising this relationship between these two systems. It is clear that what affects one, will affect the other and vice versa.
The role of the immune system is to recognize foreign and potentially harmful substances and organisms to limit their access to the intestinal wall, so the SNE under certain conditions can act as an extension of the immune system.
How do you perform this function?
For example, enteric neurons are involved in a series of defense reactions. These defense reactions include diarrhea to dilute and eliminate toxins, exaggerated propulsive activity of the colon that occurs when there are pathogens in the intestine, and vomiting.
This may have important implications in the study of pathologies involving both the enteric nervous system and the immune system as well as disorders such as Crohn's disease And ulcerative colitis.
Finally, the gastrointestinal tract also houses an extensive endocrine signaling system, and many gastrointestinal functions are under dual neuronal and endocrine control.
Related Disorders
According to Furness et al. (2012), there are several disorders related to the dysfunction of the SNE and that are classified within the enteric neuropathies, which in turn can be of several types:
- Congenital or Developmental Neuropathies: Hirschsprung disease (Colorectal agangliosis), Hypertrophic pyloric stenosis , Multiple endocrine neoplasia , Intestinal neuronal dysplasia, mitochondriopathies that affect enteric neurons, etc.
- Sporadic and acquired neuropathies: Chagas disease , Neurogenic forms of intestinal pseudo-obstruction, slow transit constipation, chronic constipation, including constipation of aging, pathogen-induced diarrhea, irritable bowel syndrome, autoimmune enteric neuritis, paraneoplastic syndrome, enteric neuritis of unknown etiology, etc.
- Secondary neuropathies, or associated with other diseases: Diabetic gastroparesis and other diabetes-related disorders of the motility, enteric neuropathy of the Parkinson's disease , Enteric neuropathy of prion disease, enteric neuropathies associated with mental retardation, or other Disorders of the central nervous system, Ischemic ischemic neuropathy, such as ischemic colitis, etc.
- Iatrogenic or drug induced neuropathies: Anti-neoplastic drug-initiated disorders, reperfusion injury associated with intestinal transplantation, opioid-induced constipation (usually caused when opiates are used to treat chronic pain).
Curiosities
Did you know that ibuprofen could disrupt the development of this system?
In a study Data are presented that raise concerns that ibuprofen may increase the risk of Hirschsprung's disease (absence of enteric nervous system) in some genetically susceptible children.
Moreover, it is known that ibuprofen increases Lipopolysaccharides (LPS) in blood that is a sign of an increase in gram-negative bacteria (many of them pathogenic to humans), caused by increased intestinal permeability, leading to immune responses and inflammation ( study ).
Did you know that the SNE is responsible for those butterflies in the stomach that you feel before different situations, like being in love?
This inter-communication of which we have spoken previously between the SNE and the brain makes it possible to"feel with the belly". That is why when we are nervous one of the most annoying symptoms that can appear are stomach problems, and even diarrhea.
For this reason, some intestinal problems such as functional and"psychological"irritable bowel syndrome have been identified, although this is a mistake, since, as we have seen throughout the article, this communication between the SNE and the CNS is very complex and Bidirectional.
This has served to give him the deserved name of" Second brain ", A primitive brain, where the emotions are in the flower of skin, or to flower of stomach, in this case.
References
- Furness, J.B. (2012). The enteric nervous system and neurogastroenterology. Nature Reviews Gastroenterology & Hepatology , 9, 286-294. Doi: 10.1038 / nrgastro.2012.32
- Sasselli, V., Pachinis, V. & Burns, A.J. (2012). The enteric nervous system. Developmental Biology, 366 , 64-73. Doi: 10.1016 / j.ydbio.2012.01.012.
- Romero-Trujillo, J.O., Frank-Márquez, N. et al. (2012). Enteric nervous system and gastrointestinal motility. Pediatric Act of Mexico, 33 (4), 207-2014.
- Furness, J.B. (2007). Enteric nervous system. Scholarpedia, 2 (10), 4064. Doi: 10.4249 / scholarpedia.4064.
- Nieman, D.C., Henson, D.A., Dumke, C.L., Oley, K. et al. (2006). Ibuprofen use, endotoxemia, inflammation, and plasma cytokines during ultramarathon competition. Brain, Behavior, and Immunity, 20 (6), 578-584. Doi: 10.1016 / j.bbi.2006.02.001.
- Schill, E.M., Lake, J.L., Tusheva, O.A., Nagy, N. et al. (2015). Ibuprofen slows migration and inhibits bowel colonization by enteric nervous system precursors in zebrafish, chick and mouse. Developmental Biology, 409 (2), 473-488. Doi: 10.1016 / j.ydbio.2015.09.023.