A model for chronic quantitative studies of colorectal sensitivity using balloon distension in conscious mice -- effects of opioid receptor agonists.
In the current study, colorectal distension (CRD) was performed in conscious mice, in order to study visceral (colon) sensitivity. Electrodes were chronically implanted into the external oblique muscle to obtain the electromyographic (EMG) response to CRD. CRD was performed using a computerized system, which inflated the balloon with air to the desired pressures. An increasing (10-80 mmHg) and a repeated (12 x 55 mmHg) phasic paradigm with distensions lasting 10 s and with 5-min intervals were used. The EMG recordings were linearly correlated to intracolonic pressures between 10 and 80 mmHg, which are characteristic of the visceromotor response (VMR). Repeated phasic distensions at 55 mmHg resulted in a stable VMR in female mice, but an increasing VMR in male mice. Interestingly, the duration of the VMR was about 5 s, which is shorter than the actual duration of the distension. U-69593 and fentanyl (selective kappa and mu opioid receptor agonists) significantly reduced the VMR at subcutaneous doses of 0.5 and 0.05 mg x kg-1, respectively. In conclusion, a CRD model for repetitive quantitative studies of colorectal sensitivity and evaluation of pharmacological modulation of visceral sensitivity in conscious mice is presented.
Larsson
M
M
Department of Integrative Pharmacology, Research Area CV & GI, Preclinical R&D, AstraZeneca, Mölndal, Sweden. marie.h.larsson@astrazenca.com
Arvidsson
S
S
Ekman
C
C
Bayati
A
A
D000009:Abdominal Muscles / Q000187:drug effects / Q000502:physiology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D003243:Consciousness; D004576:Electromyography; D005260:Female; D005283:Fentanyl / Q000494:pharmacology; D008297:Male; D051379:Mice; D023421:Models, Animal; D009119:Muscle Contraction / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010147:Pain Measurement / Q000379:methods*; D010812:Physical Stimulation; D011759:Pyrrolidines / Q000494:pharmacology; D011957:Receptors, Opioid / Q000819:agonists*; D012007:Rectum / Q000187:drug effects / Q000502:physiology*; D012727:Sex Characteristics
D000701:Analgesics, Opioid; D044482:Benzeneacetamides; D011759:Pyrrolidines; D011957:Receptors, Opioid; C045444:U 69593; D005283:Fentanyl