A model for chronic quantitative studies of colorectal sensitivity using balloon distension in conscious mice – effects of opioid receptor agonists

Larsson, Magnus; Arvidsson, Susanne; Ekman, Claes; Bayati, A.

doi:10.1046/j.1365-2982.2003.00418.x

Cited by 57 publications

(70 citation statements)

References 28 publications

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“…9 Although KOR agonists reaching the central nervous system may also induce side effects, results in rats demonstrating that KOR agonists inhibit the activity of colonic afferents via a peripheral site of action have encouraged their development. 10,11 The results in humans are consistent with findings in experimental animals, where both MOR and KOR agonists attenuate the pseudo-affective visceromotor response (VMR) induced by CRD in rats 10,[12][13][14] and mice, 15,16 suggesting a role for opioid receptors in the modulation of visceral nociception.…”

Section: Introductionsupporting

confidence: 82%

“…15,16 This response differs from that of rats, 19 which respond throughout the duration of the distending stimulus. Conceivably, mice are equipped with endogenous analgesic signalling pathways that attenuate the response.…”

Section: Introductionmentioning

confidence: 85%

“…15 Briefly, mice were anaesthetized with a mixture of DormicumÒ (midazolam 5 mg mL )1 ; Roche, Stockholm, Sweden), HypnormÒ (fentanyl citrate 0.315 mg mL )1 and fluanisone 10 mg mL )1 ; Janssen Animal Health, Beerse, Belgium) and sterile water (1 : 1 : 2) (10 mL kg )1 i.p.). A cylinder-shaped, plastic fistula containing one bipolar and one monopolar bioelectric electrode (Bioflex insulated wire AS631; Cooner Wire, Chatsworth, CA, USA) was chronically implanted in the animals.…”

Section: Surgerymentioning

confidence: 99%

“…The VMR evoked by CRD was quantified using EMG recordings of the external abdominal oblique muscle activity as previously described by Larsson et al 15 Briefly, a 2 cm balloon was gently inserted into the colon under isoflurane anaesthesia (Forene; Abbott Scandinavia AB, Stockholm, Sweden) with the base of the balloon 5 mm proximal to the anus. The catheter was fixed to the base of the tail with tape to prevent displacement.…”

Section: Crd and Emg Recordingsmentioning

confidence: 99%

“…The rationale behind using 60% as a cut-off limit is described in Larsson et al 15 The mice not reaching a 60% response above baseline were excluded from that particular experiment and, when they had failed three times in a row, were excluded from further experiments, as the electrodes were probably not working properly.…”

Section: Crd and Emg Recordingsmentioning

confidence: 99%

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Involvement of κ‐opioid receptors in visceral nociception in mice

Larsson

Bayati

Lindström

et al. 2008

Neurogastroenterology Motil

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It has been shown that the behavioural responses to chemically evoked visceral nociception are increased in transgenic mice lacking the j-opioid receptor (KOR). The aim of the present study was to evaluate the contribution of KOR in mechanically evoked visceral pain by performing colorectal distension (CRD) and monitoring the subsequent visceromotor response (VMR) in control mice (KOR +/+ ) and in mice lacking KOR (KOR )/) ). Pseudo-affective visceral pain responses were evoked in conscious mice using increasing (10-80 mmHg) and repeated (12 · 55 mmHg) phasic CRD paradigms. The resulting VMR was determined by monitoring the electromyographic activity of the abdominal muscle. The increasing and repeated CRD paradigms, respectively, evoked similar responses in both KOR +/+ and KOR )/) mice. The selective KOR-agonists U-69593 (5 and 25 mg kg )1 , s.c.) and asimadoline (25 mg kg )1 , s.c.) significantly decreased the VMR in KOR +/+ mice, while having no effect in KOR )/) mice. In contrast, the selective l-opioid receptor agonist fentanyl significantly reduced the VMR in both types of mice and appeared more efficacious in KOR )/) mice. The opioid receptor antagonist naloxone (0.3-30 mg kg )1 s.c.) did not affect the response to CRD in C57BL/6 mice at any dose tested. In conclusion, the data confirm that the KOR agonists used in this study inhibit the VMR to CRD in mice by acting via KOR receptors. In addition, the data suggest that the endogenous opioid system is not likely to modulate the VMR to mechanically evoked visceral pain in mice.

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Section: Introductionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 85%

Section: Surgerymentioning

confidence: 99%

Section: Crd and Emg Recordingsmentioning

confidence: 99%

Section: Crd and Emg Recordingsmentioning

confidence: 99%

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Involvement of κ‐opioid receptors in visceral nociception in mice

Larsson

Bayati

Lindström

et al. 2008

Neurogastroenterology Motil

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Rodent Models of Colorectal Distension

et al. 2012

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Colorectal distension (CRD) is a widely accepted, reproducible method for assessing visceral sensitivity in both clinical and pre-clinical studies. Distension of the colon mirrors the human scenario of visceral pain with regard to intensity and referral of pain in patients. There are several readouts that can be applied to the CRD protocol depending on the species being evaluated, two of which are described in this unit. CRD can be used to measure the impact of novel compounds, strain, or genetic differences as well as the effect of physical and psychological stressors on the sensitivity of the colon. Investigation of the impact of a noxious visceral stimulus (CRD) on other systems within the body can also be carried out. Given that visceral pain is a major clinical problem and one of the most common reasons patients seek out medical advice, the ability to assess this type of pain is essential to the discovery of successful treatments. This unit outlines two protocols that describe CRD of rats and mice.

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The Enteric Nervous System and Gastrointestinal Innervation: Integrated Local and Central Control

Furness

Callaghan

Rivera

et al. 2014

Advances in Experimental Medicine and Biology

655

648

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The digestive system is innervated through its connections with the central nervous system (CNS) and by the enteric nervous system (ENS) within the wall of the gastrointestinal tract. The ENS works in concert with CNS reflex and command centers and with neural pathways that pass through sympathetic ganglia to control digestive function. There is bidirectional information flow between the ENS and CNS and between the ENS and sympathetic prevertebral ganglia.The ENS in human contains 200-600 million neurons, distributed in many thousands of small ganglia, the great majority of which are found in two plexuses, the myenteric and submucosal plexuses. The myenteric plexus forms a continuous network that extends from the upper esophagus to the internal anal sphincter. Submucosal ganglia and connecting fiber bundles form plexuses in the small and large intestines, but not in the stomach and esophagus. The connections between the ENS and CNS are carried by the vagus and pelvic nerves and sympathetic pathways. Neurons also project from the ENS to prevertebral ganglia, the gallbladder, pancreas and trachea.The relative roles of the ENS and CNS differ considerably along the digestive tract. Movements of the striated muscle esophagus are determined by neural pattern generators in the CNS. Likewise the CNS has a major role in monitoring the state of the stomach and, in turn, controlling its contractile activity and acid secretion, through vago-vagal reflexes. In contrast, the ENS in the small intestine and colon contains full reflex circuits, including sensory neurons, interneurons and several classes of motor neuron, through which muscle activity, transmucosal fluid fluxes, local blood flow and other functions are controlled. The CNS has control of defecation, via the defecation centers in the lumbosacral spinal cord. The importance of the ENS is emphasized by the life-threatening effects of some ENS neuropathies. By contrast, removal of vagal or sympathetic connections with the gastrointestinal tract has minor effects on GI function. Voluntary control of defecation is exerted through pelvic connections, but cutting these connections is not life-threatening and other functions are little affected.

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A model for chronic quantitative studies of colorectal sensitivity using balloon distension in conscious mice – effects of opioid receptor agonists

Cited by 57 publications

References 28 publications

Involvement of κ‐opioid receptors in visceral nociception in mice

Involvement of κ‐opioid receptors in visceral nociception in mice

Rodent Models of Colorectal Distension

The Enteric Nervous System and Gastrointestinal Innervation: Integrated Local and Central Control

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