Effect of a stimulant of the lumbo-sacral defection centre on constipation in an animal model

      Constipation is a widespread problem that occurs particularly in old age. It is also common in children. There is no good treatment and the most common therapy remains osmotic laxatives. The pharmacological treatments that have are used, colokinetics and stimulants of secretion, have side effects, or have low margins over placebo, and none has become a treatment of choice. One of the problems that has beset the field is the lack of a well validated model of functional constipation. Here we describe a rat model in which constipation is induced by a low fibre diet. Five weeks after the low fibre diet, distension of the colon produced fewer propulsive contractions, and defecation elicited by water avoidance stress (WAS) was reduced compared to effects in rats on a normal diet. The first indication of constipation was a reduction in response to WAS at 2 weeks. We tested whether the centrally acting colokinetic, capromorelin, which stimulates the spinal cord defecation centres, could overcome the constipation of low fibre diet. Previous studies had shown capromorelin to be effective in relieving the constipation after spinal cord injury. Acutely, capromorelin was similarly effective in eliciting propulsive contraction of the colorectum in normal and constipated rats. Daily oral capromorelin was also effective in causing bowel emptying.
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