General anaesthesia-related complications of gut motility with a focus on cholinergic mechanisms, TRP channels and visceral pain

Abstract

General anesthesia produces multiple side effects. Notably, it temporarily impairs gastrointestinal motility following surgery and causes the so-called postoperative ileus (POI), a multifactorial and complex condition that develops secondary to neuromuscular failure and mainly affects the small intestine. There are currently limited medication options for POI, reflecting a lack of comprehensive understanding of the mechanisms involved in this complex condition. Notably, although acetylcholine is one of the major neurotransmitters initiating excitation-contraction coupling in the gut, cholinergic stimulation by prokinetic drugs is not very efficient in case of POI. Acetylcholine when released from excitatory motoneurones of the enteric nervous system binds to and activates M2 and M3 types of muscarinic receptors in smooth muscle myocytes. Downstream of these G protein-coupled receptors, muscarinic cation TRPC4 channels act as the major focal point of receptor-mediated signal integration, causing membrane depolarisation accompanied by action potential discharge and calcium influx via L-type Ca2+ channels for myocyte contraction. We have recently found that both inhalation (isoflurane) and intravenous (ketamine) anesthetics significantly inhibit this muscarinic cation current (termed mICAT) in ileal myocytes, even when G proteins are activated directly by intracellular GTPγS, i.e., bypassing muscarinic receptors. Here we aim to summarize Transient Receptor Potential channels and calcium signalling-related aspects of the cholinergic mechanisms in the gut and visceral pain, discuss exactly how these may be negatively impacted by general anaesthetics, while proposing the receptor-operated TRPC4 channel as a novel molecular target for the treatment of POI.

Multichannel mapping of in vivo rat uterine myometrium exhibits both high and low frequency electrical activity in non-pregnancy

“…Another limitation of this method is that smooth muscle function may be affected by anesthesia. It has been found that gastrointestinal motility can be impaired by application of general anesthetics such as isoflurane, via disruption of cholinergic mechanisms 47 , 48 . Care should be taken when determining the manner of anesthesia for future experiments, and consideration as to possible effects of anesthesia on smooth muscle function, and how this may affect results.…”

Implantable Bioelectronics for Real-timein vivoRecordings of Enteric Neural Activity

“…Given their positioning in the gut, these plexi are difficult to access, making monitoring of neural signaling within the ENS challenging. Adding difficulty is the relative inaction of the ENS under general anaesthesia ( 7 ), which results in limited and/or low-amplitude local signaling. These challenges necessitate the construction of a neural recording device that can achieve close proximity to the ENS with a low impedance to maximize signal transduction across the device interface.…”

“…As noted above, gut motility is inhibited during general anaesthesia ( 7 ), which has traditionally made acute neural recordings in the ENS a challenge. While our device was able to receive signal from the ENS in response to addition of neural stimulants, large-scale gut motility was largely absent.…”

Multichannel mapping of in vivo rat uterine myometrium exhibits both high and low frequency electrical activity in non-pregnancy

“…Another limitation of this method is that smooth muscle function may be affected by anesthesia. It has been found that gastrointestinal motility can be impaired by application of general anesthetics such as iso urane, via disruption of cholinergic mechanisms 41,42 . Care should be taken when determining the manner of anesthesia for future experiments, and consideration as to possible effects of anesthesia on smooth muscle function, and how this may affect results.…”