Assessment of visceral pain-related pseudo-affective responses to colorectal distension in mice by intracolonic manometric recordings.
Recently, a new manometric method has been proposed to quantify visceromotor responses (VMR) to colorectal distension (CRD) in rats. This method is based on monitoring pressure changes within the distending balloon during CRD. This study assesses the applicability of such a technique to the quantification of VMRs to CRD in mice. Electrical activity of the abdominal muscles and pressure changes within the distending balloon (mechanical response) were simultaneously recorded in conscious mice during CRD (phasic ascending, 10-80 mm Hg, or repetitive, 55 mm Hg). There was a clear stimulus-response relationship with a strong correlation between electrical and mechanical responses during the ascending (r(2) = 0.899, n = 7) or repetitive phasic CRD (r(2) = 0.926, n = 8). Repetitive phasic distensions (55 mm Hg) increased the mechanical and electrical responses by 71 +/- 20% and 42 +/- 16%, respectively (pulses 10-12 vs. 1-3; n = 8, both P < .01). Atropine (0.5 or 1 mg/kg, subcutaneously) did not affect the mechanical response to CRD. The mu-opioid agonist, fentanyl (0.05 mg/kg, subcutaneously), completely prevented the sensitizing response associated to repetitive distensions. These results show that noninvasive, surgery-free manometry of intracolonic pressure is a reliable method to assess VMRs to CRD in mice. The analgesic effect of compounds could be determined, indicating that the method can be used in pharmacologic studies.


CONCLUSIONS
The model presented to assess visceral pain in mice allows a broad use of this species in pharmacological studies and will be of use in the characterization of potential targets and new drugs for the treatment of human pathologies with visceral pain arising from the gut as a significant component.
Arvidsson
Susanne
S
Integrative Pharmacology-Gastrointestinal Biology, AstraZeneca R&D Mölndal, Mölndal, Sweden.
Larsson
Marie
M
Larsson
Håkan
H
Lindström
Erik
E
Martinez
Vincente
V
D000009:Abdominal Muscles / Q000503:physiopathology*; D015746:Abdominal Pain / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology; D000818:Animals; D003108:Colonic Diseases / Q000150:complications / Q000503:physiopathology*; D004108:Dilatation, Pathologic / Q000150:complications / Q000503:physiopathology; D004195:Disease Models, Animal; D004576:Electromyography; D005260:Female; D008365:Manometry / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology*; D015203:Reproducibility of Results