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Effects of autonomic nerve stimulation on colorectal motility in rats.

ABSTRACT: Several disease processes of the colon and rectum, including constipation and incontinence, have been associated with abnormalities of the autonomic nervous system. However, the autonomic innervation to the colon and rectum are not fully understood. The aims of this study were to investigate the effect of stimulation of vagus nerves, pelvic nerves (PN) and hypogastric nerves (HGN) on colorectal motility in rats.Four strain gauge transducers were implanted on the proximal colon, mid colon, distal colon and rectum to record circular muscle contractions in rats. Electrical stimulation was administered to the efferent distal ends of the cervical vagus nerve, PN and HGN. Motility index (MI) was evaluated before and during stimulation.Electrical stimulation (5-20 Hz) of the cervical vagus elicited significant contractions in the mid colon and distal colon, whereas less pronounced contractions were observed in the proximal colon. Pelvic nerves stimulation elicited significant contractions in the rectum as well as the mid colon and distal colon. Atropine treatment almost completely abolished the contractions induced by vagus nerve and PN stimulation. Hypogastric nerves stimulation caused relaxations in the rectum, mid colon and distal colon. The relaxations in response to HGN stimulation were abolished by propranolol.Vagal innervation extends to the distal colon, while the PN has projections in the distribution of the rectum through the mid colon. This suggests a pattern of dual parasympathetic innervation in the left colon. Parasympathetic fibers regulate colorectal contractions via muscarinic receptors. The HGN mainly regulates colorectal relaxations via beta-adrenoceptors.

SUBMITTER: Tong WD

PROVIDER: S-EPMC2952396 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Effects of autonomic nerve stimulation on colorectal motility in rats.

Tong W D WD Ridolfi T J TJ Kosinski L L Ludwig K K Takahashi T T

Neurogastroenterology and motility 20100113 6

<h4>Background</h4>Several disease processes of the colon and rectum, including constipation and incontinence, have been associated with abnormalities of the autonomic nervous system. However, the autonomic innervation to the colon and rectum are not fully understood. The aims of this study were to investigate the effect of stimulation of vagus nerves, pelvic nerves (PN) and hypogastric nerves (HGN) on colorectal motility in rats.<h4>Methods</h4>Four strain gauge transducers were implanted on th ...[more]

PMID: 20067587

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Project description:Although the therapeutic effects of Vagus Nerve Stimulation (VNS) have been recognized in pre-clinical and pilot clinical studies, the effect of different stimulation configurations on the cardiovascular response is still an open question, especially in the case of VNS delivered synchronously with cardiac activity. In this paper, we propose a formal mathematical methodology to analyze the acute cardiac response to different VNS configurations, jointly considering the chronotropic, dromotropic and inotropic cardiac effects. A latin hypercube sampling method was chosen to design a uniform experimental plan, composed of 75 different VNS configurations, with different values for the main parameters (current amplitude, number of delivered pulses, pulse width, interpulse period and the delay between the detected cardiac event and VNS onset). These VNS configurations were applied to 6 healthy, anesthetized sheep, while acquiring the associated cardiovascular response. Unobserved VNS configurations were estimated using a Gaussian process regression (GPR) model. In order to quantitatively analyze the effect of each parameter and their combinations on the cardiac response, the Sobol sensitivity method was applied to the obtained GPR model and inter-individual sensitivity markers were estimated using a bootstrap approach. Results highlight the dominant effect of pulse current, pulse width and number of pulses, which explain respectively 49.4%, 19.7% and 6.0% of the mean global cardiovascular variability provoked by VNS. More interestingly, results also quantify the effect of the interactions between VNS parameters. In particular, the interactions between current and pulse width provoke higher cardiac effects than the changes on the number of pulses alone (between 6 and 25% of the variability). Although the sensitivity of individual VNS parameters seems similar for chronotropic, dromotropic and inotropic responses, the interacting effects of VNS parameters provoke significantly different cardiac responses, showing the feasibility of a parameter-based functional selectivity. These results are of primary importance for the optimal, subject-specific definition of VNS parameters for a given therapy and may lead to new closed-loop methods allowing for the optimal adaptation of VNS therapy through time.

Project description:BackgroundChemotherapy-induced peripheral neuropathy is a severe side effect of chemotherapeutic agents. Vagus nerve stimulation attenuates neuroinflammation by activating the cholinergic anti-inflammatory pathway and thus may attenuate CIPN.MethodsAdult male Sprague-Dawley rats received intraperitoneal paclitaxel injection (2 mg/kg) every other day for a total of 4 injections. Three weeks later, the left cervical vagus nerve was exposed under general anesthesia, and the rats randomly received 20-min stimulation (1 V, 2 ms, 5 Hz, 30 s ON/5 min OFF) or sham stimulation. Heat and mechanical pain sensitivity was evaluated using Hargreaves and von Frey tests before and after treatment (n=12 per group per time point). Additionally, rats receiving paclitaxel or saline but no surgery were included. Expression of representative pro- and anti-inflammatory cytokines in dorsal root ganglia was assessed by Western blotting assays and immunohistochemistry.ResultsPaclitaxel significantly reduced the sensitivity for heat (withdrawal latency: paclitaxel 6.16 ± 0.54 s vs saline 9.93 ± 0.78 s, p<0.001) and mechanical pain (withdrawal frequency: paclitaxel 32.22 ± 15.51% vs saline 3.33 ± 4.92%, p<0.001). Compared with sham-stimulated rats, rats receiving vagus nerve stimulation had significantly higher sensitivity for heat (withdrawal latency: VNS 10.28 ± 1.15 s vs sham 6.27 ± 0.56 s, p<0.001) and mechanical pain (withdrawal frequency: VNS 10.00 ± 9.54% vs Sham 31.67 ± 18.99%, p=0.003) on +1 day, but not 7 days later (withdrawal latency: VNS 6.97 ± 1.13 s vs Sham 6.23 ± 0.79 s, p=0.080; withdrawal frequency: VNS 21.67 ± 11.93% vs Sham 23.33 ± 7.79%, p=0.689). Western blotting assays and immunohistochemistry revealed that interleukin-10 level was elevated in the dorsal root ganglia of rats receiving vagus nerve stimulation while no apparent changes in NF-κB or TNF-α levels were observed.ConclusionVagus nerve stimulation could transiently attenuate paclitaxel-induced hyperalgesia in rats. Future studies are needed to investigate whether stimulation with different protocols could achieve durable effects.

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Effects of autonomic nerve stimulation on colorectal motility in rats.

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Effects of autonomic nerve stimulation on colorectal motility in rats.

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